Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT02092467
• Recruitment Status: Completed
• First Posted: March 20, 2014
• Results First Posted: August 17, 2021
• Last Update Posted: August 17, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Arthritis, Rheumatoid
• Interventions: Drug: tofacitinib; Biological: adalimumab; Biological: etanercept
• Enrollment: 4372

Participant Flow

Recruitment Details
Pre-assignment Details	Study started from 14 March 2014 and completed on 22 July 2020.

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Period Title: Overall Study
Started	1457	1457	1458
Treated	1455	1456	1451
Completed	1053	998	1060
Not Completed	404	459	398
Reason Not Completed
Death	49	66	38
Lost to Follow-up	38	35	40
Global Deterioration of Health Status	1	0	0
Other	32	30	24
Withdrawal by Subject	282	327	289
Randomized but not treated	2	1	7

Baseline Characteristics

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi	Total
Arm/Group Description		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Total of all reporting groups
Overall Number of Baseline Participants		1455	1456	1451	4362
Baseline Analysis Population Description		Safety Analysis Set (SAS) included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1455 participants	1456 participants	1451 participants	4362 participants
		60.75 (6.80)	61.40 (7.07)	61.30 (7.47)	61.15 (7.12)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1455 participants	1456 participants	1451 participants	4362 participants
	Female	1169 80.3%	1124 77.2%	1117 77.0%	3410 78.2%
	Male	286 19.7%	332 22.8%	334 23.0%	952 21.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1455 participants	1456 participants	1451 participants	4362 participants
	Hispanic or Latino	438 30.1%	482 33.1%	470 32.4%	1390 31.9%
	Not Hispanic or Latino	1017 69.9%	974 66.9%	981 67.6%	2972 68.1%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	1455 participants	1456 participants	1451 participants	4362 participants
	White	1128 77.5%	1126 77.3%	1099 75.7%	3353 76.9%
	Black or African American	63 4.3%	65 4.5%	83 5.7%	211 4.8%
	Asian	65 4.5%	56 3.8%	55 3.8%	176 4.0%
	Other	199 13.7%	209 14.4%	214 14.7%	622 14.3%

Outcome Measures

1. Primary Outcome

Title	Incidence Rate of Adjudicated Malignancies Excluding Non-melanoma Skin Cancers (NMSC)
Description	Incidence rate (number of participants with event per 100 participant year [PY]) was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. Malignancy events, excluding NMSC were adjudicated by a steering committee. The risk period (RP) was the last contact date. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.
Time Frame	Baseline up to last contact date (maximum up to 72 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	All Tofacitinib	TNFi
Arm/Group Description:	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	All participants who received treatment in either tofacitinib 5 mg or tofacitinib 10 mg group BID up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed	1455	1456	2911	1451
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants with event/100 PY
	1.13; (0.87 to 1.45)	1.13; (0.86 to 1.45)	1.13; (0.94 to 1.35)	0.77; (0.55 to 1.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Tofacitinib, TNFi
	Comments	All Tofacitinib versus TNFi
	Type of Statistical Test	Non-Inferiority
	Comments	Hazard ratio (95% CI) was based on a univariate Cox proportional hazard model with treatment [All Tofacitinib (ie, tofacitinib 5 mg BID and tofacitinib 10 mg BID combined) and TNFi] as covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 95%; 1.04 to 2.09
	Estimation Comments	Primary comparison. Non-inferiority was to be claimed between All Tofacitinib and TNFi if the upper limit of the 95% CI for HR was < 1.8 (non-inferiority criterion).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib 5 mg BID, Tofacitinib 10 mg BID
	Comments	Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID
	Type of Statistical Test	Non-Inferiority
	Comments	Hazard ratio (95% CI) was based on a univariate cox proportional hazard model with treatment (tofacitinib 5 mg BID, tofacitinib 10 mg BID and TNFi) as covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.43
	Estimation Comments	Secondary comparison. Non-inferiority was to be claimed between tofacitinib 10 mg BID and tofacitinib 5 mg BID if the upper limit of the 95% CI for HR was < 2.0 (non-inferiority criterion).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib 5 mg BID, TNFi
	Comments	Tofacitinib 5 mg BID versus TNFi
	Type of Statistical Test	Other
	Comments	Hazard ratio (95% CI) was based on a univariate cox proportional hazard model with treatment (tofacitinib 5 mg BID, tofacitinib 10 mg BID and TNFi) as covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.47
	Confidence Interval	(2-Sided) 95%; 1.00 to 2.18
	Estimation Comments	Supportive analysis to the primary comparison between All Tofacitinib vs TNFi.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib 10 mg BID, TNFi
	Comments	Tofacitinib 10 mg BID versus TNFi
	Type of Statistical Test	Other
	Comments	Hazard ratio (95% CI) was based on a univariate cox proportional hazard model with treatment (tofacitinib 5 mg BID, tofacitinib 10 mg BID and TNFi) as covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 95%; 1.00 to 2.19
	Estimation Comments	Supportive analysis to the primary comparison between All Tofacitinib vs TNFi.

2. Primary Outcome

Title	Incidence Rate of Adjudicated Major Adverse Cardiovascular Events (MACE)
Description	MACE included the cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke of any classification, including reversible focal neurologic defects with imaging evidence of a new cerebral lesion consistent with ischemia or hemorrhage. Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 60 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.
Time Frame	Baseline up to last contact date (maximum up to 72 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	All Tofacitinib	TNFi
Arm/Group Description:	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	All participants who received treatment in either tofacitinib 5 mg or tofacitinib 10 mg group BID up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed	1455	1456	2911	1451
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants with event/100 PY
	0.91; (0.67 to 1.21)	1.05; (0.78 to 1.38)	0.98; (0.79 to 1.19)	0.73; (0.52 to 1.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Tofacitinib, TNFi
	Comments	All Tofacitinib versus TNFi
	Type of Statistical Test	Non-Inferiority
	Comments	Hazard ratio (95% CI) was based on a univariate Cox proportional hazard model with treatment [All Tofacitinib (ie, tofacitinib 5 mg BID and tofacitinib 10 mg BID combined) and TNFi] as covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; 0.91 to 1.94
	Estimation Comments	Primary comparison. Non-inferiority was to be claimed between All Tofacitinib and TNFi if the upper limit of the 95% CI for HR was < 1.8 (non-inferiority criterion).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib 5 mg BID, Tofacitinib 10 mg BID
	Comments	Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID
	Type of Statistical Test	Non-Inferiority
	Comments	Hazard ratio (95% CI) was based on a univariate cox proportional hazard model with treatment (tofacitinib 5 mg BID, tofacitinib 10 mg BID and TNFi) as covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.71
	Estimation Comments	Secondary Comparison. Non-inferiority was to be claimed between tofacitinib 10 mg BID and tofacitinib 5 mg BID if the upper limit of the 95% CI for HR was <2.0 (non-inferiority criterion).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib 5 mg BID, TNFi
	Comments	Tofacitinib 5 mg BID versus TNFi
	Type of Statistical Test	Other
	Comments	Hazard ratio (95% CI) was based on a univariate cox proportional hazard model with treatment (tofacitinib 5 mg BID, tofacitinib 10 mg BID and TNFi) as covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.91
	Estimation Comments	Supportive analysis to the primary comparison between All Tofacitinib vs TNFi.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tofacitinib 10 mg BID, TNFi
	Comments	Tofacitinib 10 mg BID versus TNFi
	Type of Statistical Test	Other
	Comments	Hazard ratio (95% CI) was based on a univariate cox proportional hazard model with treatment (tofacitinib 5 mg BID, tofacitinib 10 mg BID and TNFi) as covariate.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 0.94 to 2.18
	Estimation Comments	Supportive analysis to the primary comparison between All Tofacitinib vs TNFi.

3. Secondary Outcome

Title	Incidence Rate of Non-fatal Stroke
Description	Non-fatal stroke included reversible focal neurologic defects with imaging evidence of a new cerebral lesion consistent with ischemia or hemorrhage. Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 60 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.
Time Frame	Baseline up to last contact date (maximum up to 72 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed	1455	1456	1451
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants with event/100 PY
	0.27; (0.15 to 0.45)	0.33; (0.19 to 0.53)	0.34; (0.20 to 0.54)

4. Secondary Outcome

Title	Incidence Rate of Non-fatal Myocardial Infarction
Description	Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 60 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.
Time Frame	Baseline up to last contact date (maximum up to 72 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed	1455	1456	1451
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants with event/100 PY
	0.37; (0.22 to 0.57)	0.33; (0.19 to 0.53)	0.16; (0.07 to 0.31)

5. Secondary Outcome

Title	Incidence Rate of Adjudicated Opportunistic Infection Events Including Tuberculosis
Description	Opportunistic infections (OI) were reviewed and adjudicated by the opportunistic infection review committee (OIRC). Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.
Time Frame	Baseline up to last contact date (maximum up to 72 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed	1455	1456	1451
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants with event/100 PY
	0.76; (0.54 to 1.04)	0.91; (0.66 to 1.22)	0.42; (0.26 to 0.64)

6. Secondary Outcome

Title	Incidence Rate of Adjudicated Hepatic Events
Description	Hepatic events (adjudicated) included drug-induced liver injury (DILI) - probable, highly likely and definite, DILI - listed separately, DILI - cases meeting classification and severity, participants with elevations of transaminase levels greater than (>) 1* upper limit of normal (ULN), greater than or equal to (>=) 3*ULN, >=5*ULN (based on laboratory values). Incidence rate was the total number of participants with admissible events divided by total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was minimum of The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. Last contact date was maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). In case of death, last contact date was death date. First events counted within RP. Participant did not have an event or had an event outside risk period were censored at end of RP.
Time Frame	Baseline up to last contact date (maximum up to 72 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed	1455	1456	1451
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants with event/100 PY
	0.90; (0.66 to 1.20)	1.51; (1.18 to 1.91)	0.70; (0.49 to 0.97)

7. Secondary Outcome

Title	Incidence Rate of Adjudicated Cardiovascular Events Other Than Major Adverse Cardiovascular Events (MACE)
Description	Cardiovascular events (adjudicated) were death (coronary and non-coronary), MI, all coronary revascularization, unstable angina, new ischemic heart disease, stroke (fatal and non-fatal), transient ischemic attack (TIA), congestive heart failure (CHF), peripheral arterial vascular disease (PAVD), deep vein thrombosis, pulmonary embolism, arterial embolism, arterial thrombosis. Incidence rate was total number of participants with admissible events divided by total (for all qualifying participants) time at risk for cohort/treatment group of interest. Risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. Last contact date was maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). In case of death, last contact date was death date. First events counted within RP. Participant did not have an event or had an event outside risk period were censored at end of RP.
Time Frame	Baseline up to last contact date (maximum up to 72 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed	1455	1456	1451
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants with event/100 PY
	1.21; (0.92 to 1.55)	1.45; (1.13 to 1.83)	1.05; (0.78 to 1.38)

8. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	AE was any untoward medical occurrence post treatment; event need not necessarily had causal relationship with treatment or usage. SAE: any untoward medical occurrence at any dose: resulted in death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in congenital anomaly. TEAE: event that occurred for first time during effective duration of treatment and not seen prior to start of treatment or event seen prior to start of treatment but increase in severity during treatment. Risk period (RP) for AE: minimum of last contact date or last study treatment dose date+28 days. RP for SAEs: last contact date. Last contact date was maximum: AE start, AE stop, last study visit, withdrawal and telephone contact. In case of death, last contact was death date. First events counted within RP. Participant did not have event or had event outside risk period were censored at end of RP.
Time Frame	AEs: Baseline up to minimum of last contact date or last study treatment dose date+28 days (maximum up to 72 months); SAEs: Baseline up to minimum of last contact date (maximum up to 72 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed	1455	1456	1451
Measure Type: Count of Participants; Unit of Measure: Participants
AEs	1333 91.6%	1344 92.3%	1308 90.1%
SAEs	373 25.6%	420 28.8%	339 23.4%

9. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormal Laboratory Parameters
Description	Clinically significant laboratory abnormalities: Hematology: hemoglobin, hematocrit, erythrocytes with primary criteria as less than [<] 0.8* lower limit of normal [LLN]), platelets (<0.5* LLN; >1.75* ULN), leukocytes (<0.6*LLN; >1.5*ULN), lymphocytes, lymphocytes/leukocytes, neutrophils, neutrophils/leukocytes (<0.8*LLN; >1.2*ULN), eosinophils, eosinophils/leukocytes, monocytes, monocytes/leukocytes (>1.2*ULN); urinalysis: urine glucose, urine protein, urine hemoglobin, and leukocyte esterase (>=1); chemistry: bilirubin, indirect bilirubin (>1.5*ULN) aspartate aminotransferase, alanine aminotransferase (>3.0*ULN), creatinine, triglycerides, cholesterol (>1.3*ULN) and HDL cholesterol (<0.8*LLN). Risk period (RP) was minimum of last contact date or last study treatment dose date+28 days. Last contact date was (date of death or maximum of dates: AE start, AE stop, last study visit, withdrawal, telephone contact). Participants without event or event outside RP were censored at end of RP.
Time Frame	Baseline up to last contact date (maximum up to 72 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all participants from SAS with an abnormal baseline with at least one observation of the given laboratory test while on study treatment or during lag time.

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed	919	911	915
Measure Type: Count of Participants; Unit of Measure: Participants
	238 25.9%	252 27.7%	167 18.3%

10. Secondary Outcome

Title	Incidence Rate of Adjudicated All-Cause Deaths
Description	All-cause death was defined as the death due to any cause during the course of study. Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. Incidence rate of all-cause deaths (adjudicated by Adjudication Committee) was reported in this outcome measure. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.
Time Frame	Baseline up to last contact date (maximum up to 72 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed	1455	1456	1451
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants with event/100 PY
Deaths-Total	0.50; (0.33 to 0.74)	0.80; (0.57 to 1.09)	0.34; (0.20 to 0.54)
Deaths - Infections	0.08; (0.02 to 0.20)	0.18; (0.08 to 0.35)	0.06; (0.01 to 0.17)
Deaths - Cardiovascular Events	0.25; (0.13 to 0.43)	0.41; (0.25 to 0.63)	0.20; (0.10 to 0.36)
Deaths - Malignancies	0.10; (0.03 to 0.23)	0.00; (0.00 to 0.08)	0.02; (0.00 to 0.11)
Deaths - Other Causes	0.08; (0.02 to 0.20)	0.21; (0.10 to 0.38)	0.06; (0.01 to 0.17)

11. Secondary Outcome

Title	Number of Participants With Reasons For Permanent or Temporary Discontinuation of Study Medication
Description	Number of participants who permanent or temporary discontinued study medication due to any AE, treatment related AEs, Coronavirus disease 2019 (COVID 19) related AEs, and herpes zoster were reported. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.
Time Frame	Baseline up to last contact date (maximum up to 72 months)

Outcome Measure Data

Analysis Population Description

SAS included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed	1455	1456	1451
Measure Type: Count of Participants; Unit of Measure: Participants
Permanent discontinuation: AE	210 14.4%	304 20.9%	210 14.5%
Temporary discontinuation: AEs	665 45.7%	736 50.5%	576 39.7%
Permanent discontinuation: treatment related AE	111 7.6%	179 12.3%	114 7.9%
Temporary discontinuation: treatment related AE	407 28.0%	458 31.5%	297 20.5%
Permanent discontinuation: COVID-19 Related AEs	0 0.0%	1 0.1%	0 0.0%
Temporary discontinuation: COVID-19 Related AEs	0 0.0%	1 0.1%	1 0.1%
Permanent discontinuation: Herpes Zoster	6 0.4%	13 0.9%	2 0.1%
Temporary discontinuation: Herpes Zoster	104 7.1%	110 7.6%	33 2.3%

12. Secondary Outcome

Title	Change From Baseline in Disease Activity Score 28-4 (DAS28-4) C-reactive Protein (CRP) at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63
Description	DAS28 is a measure of disease activity in participants with rheumatoid arthritis based on a 28-joint assessment. DAS28-4 (CRP) was calculated from number of painful joints out of 28 joints (TJC28) and number of swollen joints out of 28 joints (SJC28), CRP (milligrams per liter [mg/L]) and patient's global assessment of disease activity (PtGA) on a 100 mm Visual Analog Scale (VAS) (scores ranging from 0 millimeter [mm] [very well] to 100 mm [worst], higher scores indicated worse health condition). Total DAS28-4 (CRP) score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (CRP) <= 3.2 indicates low disease activity and > 3.2 to <=5.1 indicates moderate disease activity, >5.1 indicates high disease activity, and DAS28-4 (CRP) < 2.6 indicates remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96; ln = natural logarithm, sqrt = square root.
Time Frame	Baseline, Months 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants randomized and received at least one dose of drug. Mixed model for repeated measures used without imputation for missing values. Analyses included data while participants were receiving drug. Only visits with N > 50 participants in each treatment group included in analyses. Number of Participants Analyzed: number of participants included in mixed model for repeated measures. Number Analyzed: number of participants evaluable for each specified time point.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1409	1391	1386
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Change at Month 2	Number Analyzed	1325 participants	1301 participants	1316 participants
		-2.00 (0.03)	-2.14 (0.03)	-1.89 (0.03)
Change at Month 3	Number Analyzed	1367 participants	1328 participants	1317 participants
		-2.28 (0.03)	-2.42 (0.03)	-2.19 (0.03)
Change at Month 6	Number Analyzed	1336 participants	1298 participants	1294 participants
		-2.50 (0.03)	-2.68 (0.03)	-2.40 (0.03)
Change at Month 9	Number Analyzed	1286 participants	1246 participants	1245 participants
		-2.64 (0.03)	-2.80 (0.03)	-2.54 (0.03)
Change at Month 12	Number Analyzed	1254 participants	1204 participants	1197 participants
		-2.70 (0.03)	-2.85 (0.03)	-2.60 (0.03)
Change at Month 15	Number Analyzed	1218 participants	1171 participants	1174 participants
		-2.78 (0.03)	-2.93 (0.03)	-2.67 (0.03)
Change at Month 18	Number Analyzed	1184 participants	1121 participants	1138 participants
		-2.78 (0.03)	-2.95 (0.03)	-2.76 (0.03)
Change at Month 21	Number Analyzed	1169 participants	1076 participants	1115 participants
		-2.82 (0.03)	-2.97 (0.03)	-2.76 (0.03)
Change at Month 24	Number Analyzed	1134 participants	1051 participants	1097 participants
		-2.82 (0.03)	-2.99 (0.03)	-2.77 (0.03)
Change at Month 27	Number Analyzed	1099 participants	1015 participants	1045 participants
		-2.91 (0.03)	-3.03 (0.03)	-2.81 (0.03)
Change at Month 30	Number Analyzed	1073 participants	999 participants	1039 participants
		-2.92 (0.03)	-3.03 (0.03)	-2.89 (0.03)
Change at Month 33	Number Analyzed	1055 participants	974 participants	1037 participants
		-2.89 (0.03)	-3.03 (0.03)	-2.89 (0.03)
Change at Month 36	Number Analyzed	1029 participants	951 participants	1014 participants
		-2.91 (0.03)	-2.98 (0.03)	-2.88 (0.03)
Change at Month 39	Number Analyzed	984 participants	888 participants	960 participants
		-2.96 (0.03)	-2.97 (0.03)	-2.91 (0.03)
Change at Month 42	Number Analyzed	851 participants	768 participants	831 participants
		-2.95 (0.03)	-3.05 (0.03)	-2.93 (0.03)
Change at Month 45	Number Analyzed	710 participants	642 participants	673 participants
		-2.94 (0.04)	-2.96 (0.04)	-2.97 (0.04)
Change at Month 48	Number Analyzed	567 participants	506 participants	537 participants
		-2.98 (0.04)	-2.99 (0.04)	-2.93 (0.04)
Change at Month 51	Number Analyzed	458 participants	419 participants	414 participants
		-3.00 (0.04)	-2.95 (0.04)	-2.96 (0.04)
Change at Month 54	Number Analyzed	363 participants	329 participants	322 participants
		-2.99 (0.04)	-3.01 (0.05)	-2.99 (0.05)
Change at Month 57	Number Analyzed	263 participants	240 participants	247 participants
		-2.97 (0.05)	-2.93 (0.05)	-3.02 (0.05)
Change at Month 60	Number Analyzed	182 participants	182 participants	166 participants
		-3.09 (0.06)	-2.94 (0.06)	-3.01 (0.06)
Change at Month 63	Number Analyzed	106 participants	108 participants	96 participants
		-3.07 (0.08)	-2.99 (0.07)	-3.05 (0.08)

13. Secondary Outcome

Title	Change From Baseline in Simplified Disease Activity Index (SDAI) Score at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63
Description	SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and physician's global assessment of health (PhyGA) both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/L). SDAI total score ranges from 0 to 86 with higher score indicating greater disease activity. SDAI <=3.3 indicates disease remission, >3.4 to 11 indicates low disease activity >11 to 26 indicates moderate disease activity, and >26 indicates high disease activity. SDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10 + CRP/10.
Time Frame	Baseline, Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

Outcome Measure Data

Analysis Population Description

FAS: all participants randomized and received at least one dose of drug. Mixed model for repeated measures used without imputation for missing values. Analyses included data while participants were receiving drug. Only visits with N > 50 participants in each treatment group included in analyses. Number of Participants Analyzed: number of participants included in mixed model for repeated measures. Number Analyzed: number of participants evaluable for each specified time point.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1378	1356	1346
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Change at Month 2	Number Analyzed	1272 participants	1257 participants	1258 participants
		-22.95 (0.33)	-23.84 (0.33)	-22.24 (0.33)
Change at Month 3	Number Analyzed	1321 participants	1280 participants	1273 participants
		-25.73 (0.30)	-26.81 (0.30)	-25.26 (0.30)
Change at Month 6	Number Analyzed	1288 participants	1245 participants	1244 participants
		-27.63 (0.28)	-28.93 (0.28)	-27.21 (0.28)
Change at Month 9	Number Analyzed	1244 participants	1204 participants	1197 participants
		-28.81 (0.28)	-30.07 (0.28)	-28.29 (0.28)
Change at Month 12	Number Analyzed	1215 participants	1168 participants	1143 participants
		-29.56 (0.27)	-30.46 (0.27)	-28.71 (0.27)
Change at Month 15	Number Analyzed	1172 participants	1128 participants	1129 participants
		-30.20 (0.25)	-31.15 (0.26)	-29.30 (0.26)
Change at Month 18	Number Analyzed	1149 participants	1085 participants	1092 participants
		-30.14 (0.26)	-31.29 (0.26)	-30.18 (0.26)
Change at Month 21	Number Analyzed	1138 participants	1040 participants	1072 participants
		-30.42 (0.26)	-31.46 (0.26)	-30.36 (0.26)
Change at Month 24	Number Analyzed	1092 participants	1010 participants	1051 participants
		-30.51 (0.26)	-31.56 (0.26)	-30.33 (0.26)
Change at month 27	Number Analyzed	1056 participants	979 participants	1002 participants
		-31.16 (0.25)	-31.85 (0.26)	-30.53 (0.26)
Change at Month 30	Number Analyzed	1046 participants	970 participants	996 participants
		-31.27 (0.25)	-32.02 (0.25)	-31.24 (0.25)
Change at Month 33	Number Analyzed	1027 participants	947 participants	997 participants
		-31.06 (0.26)	-31.91 (0.26)	-31.20 (0.26)
Change at Month 36	Number Analyzed	994 participants	917 participants	978 participants
		-31.26 (0.26)	-31.52 (0.27)	-31.09 (0.26)
Change at Month 39	Number Analyzed	954 participants	857 participants	920 participants
		-31.77 (0.25)	-31.51 (0.26)	-31.36 (0.26)
Change at Month 42	Number Analyzed	819 participants	733 participants	800 participants
		-31.62 (0.27)	-32.09 (0.28)	-31.24 (0.27)
Change at Month 45	Number Analyzed	692 participants	617 participants	646 participants
		-31.27 (0.29)	-31.67 (0.30)	-31.85 (0.30)
Change at Month 48	Number Analyzed	547 participants	485 participants	522 participants
		-31.87 (0.31)	-31.59 (0.32)	-31.68 (0.32)
Change at Month 51	Number Analyzed	438 participants	406 participants	400 participants
		-32.15 (0.33)	-31.52 (0.34)	-31.72 (0.34)
Change at Month 54	Number Analyzed	347 participants	316 participants	314 participants
		-31.91 (0.33)	-32.33 (0.35)	-31.95 (0.35)
Change at Month 57	Number Analyzed	253 participants	235 participants	242 participants
		-31.58 (0.41)	-31.61 (0.42)	-31.98 (0.42)
Change at Month 60	Number Analyzed	174 participants	179 participants	161 participants
		-32.84 (0.46)	-31.57 (0.46)	-32.23 (0.48)
Change at Month 63	Number Analyzed	102 participants	107 participants	95 participants
		-32.27 (0.63)	-32.12 (0.62)	-32.27 (0.66)

14. Secondary Outcome

Title	Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63
Description	CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76 with higher score indicating greater disease activity. CDAI <=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity. CDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10.
Time Frame	Baseline, Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

Outcome Measure Data

Analysis Population Description

FAS: all participants randomized and received at least one dose of drug. Mixed model for repeated measures used without imputation for missing values. Analyses included data while participants were receiving drug. Only visits with N > 50 participants in each treatment group included in analyses. Number of Participants Analyzed: number of participants included in mixed model for repeated measures. Number Analyzed: number of participants evaluable for each specified time point.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1378	1356	1348
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Change at Month 2	Number Analyzed	1272 participants	1258 participants	1264 participants
		-21.99 (0.32)	-22.84 (0.32)	-21.30 (0.32)
Change at Month 3	Number Analyzed	1325 participants	1281 participants	1276 participants
		-24.76 (0.29)	-25.77 (0.29)	-24.29 (0.30)
Change at Month 6	Number Analyzed	1292 participants	1246 participants	1249 participants
		-26.59 (0.27)	-27.82 (0.28)	-26.21 (0.28)
Change at Month 9	Number Analyzed	1245 participants	1207 participants	1200 participants
		-27.78 (0.27)	-29.03 (0.27)	-27.30 (0.27)
Change at Month 12	Number Analyzed	1217 participants	1169 participants	1146 participants
		-28.52 (0.26)	-29.38 (0.26)	-27.73 (0.26)
Change at Month 15	Number Analyzed	1177 participants	1129 participants	1135 participants
		-29.17 (0.25)	-30.06 (0.25)	-28.38 (0.25)
Change at Month 18	Number Analyzed	1152 participants	1086 participants	1096 participants
		-29.12 (0.25)	-30.21 (0.26)	-29.15 (0.25)
Change at Month 21	Number Analyzed	1141 participants	1041 participants	1075 participants
		-29.45 (0.25)	-30.49 (0.26)	-29.40 (0.25)
Change at Month 24	Number Analyzed	1093 participants	1013 participants	1055 participants
		-29.54 (0.25)	-30.49 (0.26)	-29.39 (0.25)
Change at Month 27	Number Analyzed	1058 participants	979 participants	1011 participants
		-30.16 (0.24)	-30.82 (0.25)	-29.54 (0.25)
Change at Month 30	Number Analyzed	1049 participants	970 participants	1002 participants
		-30.27 (0.24)	-30.99 (0.25)	-30.24 (0.25)
Change at Month 33	Number Analyzed	1034 participants	951 participants	1000 participants
		-30.05 (0.25)	-30.85 (0.25)	-30.23 (0.25)
Change at Month 36	Number Analyzed	999 participants	920 participants	982 participants
		-30.29 (0.25)	-30.50 (0.26)	-30.14 (0.25)
Change at Month 39	Number Analyzed	958 participants	858 participants	923 participants
		-30.78 (0.24)	-30.49 (0.25)	-30.35 (0.25)
Change at Month 42	Number Analyzed	820 participants	736 participants	801 participants
		-30.66 (0.26)	-31.05 (0.27)	-30.25 (0.26)
Change at Month 45	Number Analyzed	694 participants	618 participants	650 participants
		-30.28 (0.28)	-30.68 (0.29)	-30.83 (0.29)
Change at Month 48	Number Analyzed	547 participants	487 participants	522 participants
		-30.85 (0.30)	-30.57 (0.32)	-30.69 (0.31)
Change at Month 51	Number Analyzed	440 participants	407 participants	401 participants
		-31.09 (0.32)	-30.50 (0.33)	-30.74 (0.33)
Change at Month 54	Number Analyzed	347 participants	317 participants	314 participants
		-31.03 (0.32)	-31.38 (0.33)	-31.02 (0.33)
Change at Month 57	Number Analyzed	254 participants	236 participants	242 participants
		-30.62 (0.40)	-30.75 (0.41)	-30.95 (0.41)
Change at Month 60	Number Analyzed	175 participants	179 participants	161 participants
		-31.74 (0.45)	-30.57 (0.45)	-31.31 (0.47)
Change at Month 63	Number Analyzed	102 participants	107 participants	95 participants
		-31.23 (0.58)	-31.08 (0.57)	-31.65 (0.60)

15. Secondary Outcome

Title	Percentage of Participants Who Achieved Observed American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean Remission Criteria
Description	ACR-EULAR Boolean-based definition of remission participant must satisfy all of the following: TJC28 <=1, SJC28 <=1, CRP <=10 mg/L, PtGA on a 0-100 mm scale, higher scores indicate greater affection due to disease activity.
Time Frame	Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

Outcome Measure Data

Analysis Population Description

FAS included all participants randomized in study and received at least one dose of randomized investigational drug. Analyses included data while participants were receiving the study drug. 'Number Analyzed' signifies number of participants evaluable for each specified time point. Last Observation Carried Forward (LOCF) applied for missing components and composite binary outcome was calculated. The percentages were calculated using numbers of participants evaluable at each visit as denominators.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1455	1456	1451
Measure Type: Number; Unit of Measure: percentage of participants
Month 2	Number Analyzed	1356 participants	1342 participants	1368 participants
		3.83	4.99	3.22
Month 3	Number Analyzed	1432 participants	1424 participants	1427 participants
		5.73	7.72	6.10
Month 6	Number Analyzed	1417 participants	1398 participants	1411 participants
		9.10	10.66	7.80
Month 9	Number Analyzed	1392 participants	1349 participants	1384 participants
		10.85	12.60	8.96
Month 12	Number Analyzed	1372 participants	1332 participants	1360 participants
		11.22	13.06	9.12
Month 15	Number Analyzed	1353 participants	1311 participants	1342 participants
		12.56	15.18	10.28
Month 18	Number Analyzed	1322 participants	1284 participants	1316 participants
		12.10	16.04	11.78
Month 21	Number Analyzed	1302 participants	1255 participants	1294 participants
		12.90	15.22	13.45
Month 24	Number Analyzed	1287 participants	1226 participants	1273 participants
		13.60	15.99	13.35
Month 27	Number Analyzed	1269 participants	1211 participants	1255 participants
		13.24	17.59	14.82
Month 30	Number Analyzed	1248 participants	1191 participants	1237 participants
		13.46	16.96	14.31
Month 33	Number Analyzed	1232 participants	1177 participants	1221 participants
		13.88	15.97	14.82
Month 36	Number Analyzed	1206 participants	1162 participants	1211 participants
		14.51	16.18	14.53
Month 39	Number Analyzed	1183 participants	1140 participants	1201 participants
		13.78	14.30	15.15
Month 42	Number Analyzed	1163 participants	1110 participants	1179 participants
		14.79	15.41	15.01
Month 45	Number Analyzed	1021 participants	970 participants	1023 participants
		14.89	15.46	15.74
Month 48	Number Analyzed	865 participants	806 participants	839 participants
		15.14	13.90	17.28
Month 51	Number Analyzed	698 participants	671 participants	689 participants
		14.33	15.50	16.26
Month 54	Number Analyzed	564 participants	548 participants	550 participants
		14.01	16.42	16.36
Month 57	Number Analyzed	444 participants	445 participants	431 participants
		15.54	14.16	15.08
Month 60	Number Analyzed	327 participants	330 participants	321 participants
		11.31	12.73	15.58
Month 63	Number Analyzed	221 participants	230 participants	223 participants
		11.76	16.96	15.25
Month 66	Number Analyzed	122 participants	131 participants	122 participants
		9.02	16.79	13.11
Month 69	Number Analyzed	46 participants	46 participants	48 participants
		13.04	19.57	14.58
Month 72	Number Analyzed	12 participants	18 participants	15 participants
		8.33	22.22	13.33

16. Secondary Outcome

Title	Percentage of Participants With Simplified Disease Activity Index (SDAI) Less Than or Equal to (<=) 3.3
Description	SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/L). SDAI total score ranges from 0 to 86 with higher score indicating greater disease activity. SDAI <=3.3 indicates disease remission, >3.4 to 11 indicates low disease activity >11 to 26 indicates moderate disease activity, and >26 indicates high disease activity. SDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10 + CRP/10.
Time Frame	Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

Outcome Measure Data

Analysis Population Description

FAS included all participants randomized in the study and received at least one dose of investigational drug. Analyses included the data while the participants were receiving the study drug. Here, 'Number Analyzed' signifies number of participants evaluable for each specified time point. LOCF was applied for missing components, and then composite binary outcome was calculated. The percentages were calculated using the numbers of participants evaluable at each visit as the denominators.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1455	1456	1451
Measure Type: Number; Unit of Measure: percentage of participants
Month 2	Number Analyzed	1320 participants	1308 participants	1325 participants
		4.62	7.03	4.15
Month 3	Number Analyzed	1425 participants	1409 participants	1416 participants
		9.19	11.14	7.84
Month 6	Number Analyzed	1414 participants	1391 participants	1404 participants
		12.38	14.23	10.40
Month 9	Number Analyzed	1390 participants	1349 participants	1380 participants
		15.90	17.72	12.75
Month 12	Number Analyzed	1372 participants	1332 participants	1358 participants
		15.89	18.69	13.92
Month 15	Number Analyzed	1353 participants	1311 participants	1340 participants
		18.26	20.29	15.90
Month 18	Number Analyzed	1322 participants	1284 participants	1316 participants
		18.68	21.96	16.79
Month 21	Number Analyzed	1302 participants	1255 participants	1294 participants
		20.89	22.07	17.93
Month 24	Number Analyzed	1287 participants	1226 participants	1273 participants
		20.44	22.76	18.93
Month 27	Number Analyzed	1269 participants	1211 participants	1255 participants
		21.91	23.62	21.12
Month 30	Number Analyzed	1248 participants	1191 participants	1237 participants
		21.31	23.68	21.91
Month 33	Number Analyzed	1232 participants	1177 participants	1221 participants
		21.43	25.06	22.19
Month 36	Number Analyzed	1206 participants	1162 participants	1211 participants
		22.47	24.35	21.80
Month 39	Number Analyzed	1183 participants	1140 participants	1201 participants
		22.99	24.21	21.48
Month 42	Number Analyzed	1163 participants	1110 participants	1179 participants
		24.59	24.23	23.41
Month 45	Number Analyzed	1021 participants	970 participants	1023 participants
		25.27	23.20	23.26
Month 48	Number Analyzed	865 participants	806 participants	839 participants
		25.32	23.20	24.20
Month 51	Number Analyzed	698 participants	671 participants	689 participants
		23.35	23.85	24.24
Month 54	Number Analyzed	564 participants	548 participants	550 participants
		22.34	24.09	24.55
Month 57	Number Analyzed	444 participants	445 participants	431 participants
		24.10	23.82	24.83
Month 60	Number Analyzed	327 participants	330 participants	321 participants
		18.65	20.30	25.23
Month 63	Number Analyzed	221 participants	230 participants	223 participants
		19.00	23.48	23.32
Month 66	Number Analyzed	122 participants	131 participants	122 participants
		14.75	21.37	20.49
Month 69	Number Analyzed	46 participants	46 participants	48 participants
		17.39	17.39	22.92
Month 72	Number Analyzed	12 participants	18 participants	15 participants
		16.67	22.22	13.33

17. Secondary Outcome

Title	Percentage of Participants With Clinical Disease Activity Index (CDAI) <=2.8
Description	CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76 with higher score indicating greater disease activity. CDAI <=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity. CDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10.
Time Frame	Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

Outcome Measure Data

Analysis Population Description

FAS included all participants randomized in the study and received at least one dose of investigational drug. Analyses included the data while the participants were receiving the study drug. Here, 'Number Analyzed' signifies number of participants evaluable for each specified time point. LOCF was applied for missing components, and then composite binary outcome was calculated. The percentages were calculated using the numbers of participants evaluable at each visit as the denominators.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1455	1456	1451
Measure Type: Number; Unit of Measure: percentage of participants
Month 2	Number Analyzed	1320 participants	1311 participants	1330 participants
		4.70	7.40	4.36
Month 3	Number Analyzed	1425 participants	1410 participants	1417 participants
		9.26	11.06	7.76
Month 6	Number Analyzed	1414 participants	1391 participants	1405 participants
		12.87	14.31	10.32
Month 9	Number Analyzed	1390 participants	1349 participants	1381 participants
		15.76	18.09	13.25
Month 12	Number Analyzed	1372 participants	1332 participants	1359 participants
		16.33	18.62	14.64
Month 15	Number Analyzed	1353 participants	1311 participants	1341 participants
		18.03	21.36	16.41
Month 18	Number Analyzed	1322 participants	1284 participants	1316 participants
		19.82	22.12	17.93
Month 21	Number Analyzed	1302 participants	1255 participants	1294 participants
		21.35	22.55	18.70
Month 24	Number Analyzed	1287 participants	1226 participants	1273 participants
		20.44	22.76	19.48
Month 27	Number Analyzed	1269 participants	1211 participants	1255 participants
		22.77	23.29	21.51
Month 30	Number Analyzed	1248 participants	1191 participants	1237 participants
		21.88	24.18	22.31
Month 33	Number Analyzed	1232 participants	1177 participants	1221 participants
		22.24	25.91	22.36
Month 36	Number Analyzed	1206 participants	1162 participants	1211 participants
		23.22	25.30	21.64
Month 39	Number Analyzed	1183 participants	1140 participants	1201 participants
		23.92	24.30	21.90
Month 42	Number Analyzed	1163 participants	1110 participants	1179 participants
		25.02	24.95	23.66
Month 45	Number Analyzed	1021 participants	970 participants	1023 participants
		25.95	24.23	23.85
Month 48	Number Analyzed	865 participants	806 participants	839 participants
		25.55	24.44	24.31
Month 51	Number Analyzed	698 participants	671 participants	689 participants
		24.50	24.89	25.11
Month 54	Number Analyzed	564 participants	548 participants	550 participants
		23.23	25.00	25.45
Month 57	Number Analyzed	444 participants	445 participants	431 participants
		24.32	24.04	25.75
Month 60	Number Analyzed	327 participants	330 participants	321 participants
		19.88	20.91	26.48
Month 63	Number Analyzed	221 participants	230 participants	223 participants
		20.81	22.17	22.87
Month 66	Number Analyzed	122 participants	131 participants	122 participants
		13.93	22.14	17.21
Month 69	Number Analyzed	46 participants	46 participants	48 participants
		19.57	19.57	18.75
Month 72	Number Analyzed	12 participants	18 participants	15 participants
		16.67	22.22	13.33

18. Secondary Outcome

Title	Percentage of Participants With Simplified Disease Activity Index (SDAI) <=11
Description	SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/L). SDAI total score ranges from 0 to 86 with higher score indicating greater disease activity. SDAI <=3.3 indicates disease remission, >3.4 to 11 indicates low disease activity >11 to 26 indicates moderate disease activity, and >26 indicates high disease activity. SDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10 + CRP/10.
Time Frame	Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

Outcome Measure Data

Analysis Population Description

FAS included all participants randomized in the study and received at least one dose of investigational drug. Analyses included the data while the participants were receiving the study drug. Here, 'Number Analyzed' signifies number of participants evaluable for each specified time point. LOCF was applied for missing components, and then composite binary outcome was calculated. The percentages were calculated using the numbers of participants evaluable at each visit as the denominators.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1455	1456	1451
Measure Type: Number; Unit of Measure: percentage of participants
Month 2	Number Analyzed	1320 participants	1308 participants	1325 participants
		30.76	35.02	28.08
Month 3	Number Analyzed	1425 participants	1409 participants	1416 participants
		41.47	45.00	37.99
Month 6	Number Analyzed	1414 participants	1391 participants	1404 participants
		50.85	53.56	45.80
Month 9	Number Analyzed	1390 participants	1349 participants	1380 participants
		56.40	59.82	52.90
Month 12	Number Analyzed	1372 participants	1332 participants	1358 participants
		57.87	61.11	54.93
Month 15	Number Analyzed	1353 participants	1311 participants	1340 participants
		61.12	63.92	57.39
Month 18	Number Analyzed	1322 participants	1284 participants	1316 participants
		62.10	65.19	60.41
Month 21	Number Analyzed	1302 participants	1255 participants	1294 participants
		62.75	65.26	61.21
Month 24	Number Analyzed	1287 participants	1226 participants	1273 participants
		63.17	66.15	61.59
Month 27	Number Analyzed	1269 participants	1211 participants	1255 participants
		65.17	66.97	63.67
Month 30	Number Analyzed	1248 participants	1191 participants	1237 participants
		67.23	68.35	65.64
Month 33	Number Analyzed	1232 participants	1177 participants	1221 participants
		65.75	68.82	65.36
Month 36	Number Analyzed	1206 participants	1162 participants	1211 participants
		67.33	66.61	65.48
Month 39	Number Analyzed	1183 participants	1140 participants	1201 participants
		69.74	67.11	66.03
Month 42	Number Analyzed	1163 participants	1110 participants	1179 participants
		68.96	70.72	66.41
Month 45	Number Analyzed	1021 participants	970 participants	1023 participants
		68.36	68.97	67.55
Month 48	Number Analyzed	865 participants	806 participants	839 participants
		67.28	64.76	67.94
Month 51	Number Analyzed	698 participants	671 participants	689 participants
		67.91	67.51	67.78
Month 54	Number Analyzed	564 participants	548 participants	550 participants
		64.89	68.61	68.00
Month 57	Number Analyzed	444 participants	445 participants	431 participants
		63.51	66.29	68.21
Month 60	Number Analyzed	327 participants	330 participants	321 participants
		63.30	66.67	64.17
Month 63	Number Analyzed	221 participants	230 participants	223 participants
		61.54	68.26	64.57
Month 66	Number Analyzed	122 participants	131 participants	122 participants
		59.02	71.76	59.02
Month 69	Number Analyzed	46 participants	46 participants	48 participants
		60.87	65.22	68.75
Month 72	Number Analyzed	12 participants	18 participants	15 participants
		50.00	66.67	60.00

19. Secondary Outcome

Title	Percentage of Participants With Clinical Disease Activity Index (CDAI) <=10
Description	CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76 with higher score indicating greater disease activity. CDAI <=2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity. CDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10.
Time Frame	Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

Outcome Measure Data

Analysis Population Description

FAS included all participants randomized in the study and received at least one dose of investigational drug. Analyses included the data while the participants were receiving the study drug. Here, 'Number Analyzed' signifies number of participants evaluable for each specified time point. LOCF was applied for missing components, and then composite binary outcome was calculated. The percentages were calculated using the numbers of participants evaluable at each visit as the denominators.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1455	1456	1451
Measure Type: Number; Unit of Measure: percentage of participants
Month 2	Number Analyzed	1320 participants	1311 participants	1330 participants
		29.47	34.25	26.92
Month 3	Number Analyzed	1425 participants	1410 participants	1417 participants
		40.07	43.90	35.99
Month 6	Number Analyzed	1414 participants	1391 participants	1405 participants
		49.36	51.83	43.63
Month 9	Number Analyzed	1390 participants	1349 participants	1381 participants
		55.40	58.78	50.91
Month 12	Number Analyzed	1372 participants	1332 participants	1359 participants
		56.56	59.38	53.57
Month 15	Number Analyzed	1353 participants	1311 participants	1341 participants
		60.31	62.70	55.93
Month 18	Number Analyzed	1322 participants	1284 participants	1316 participants
		60.51	64.02	59.42
Month 21	Number Analyzed	1302 participants	1255 participants	1294 participants
		61.37	64.94	60.20
Month 24	Number Analyzed	1287 participants	1226 participants	1273 participants
		62.78	65.25	61.19
Month 27	Number Analyzed	1269 participants	1211 participants	1255 participants
		64.93	66.39	62.87
Month 30	Number Analyzed	1248 participants	1191 participants	1237 participants
		67.15	67.84	65.00
Month 33	Number Analyzed	1232 participants	1177 participants	1221 participants
		65.50	67.71	65.03
Month 36	Number Analyzed	1206 participants	1162 participants	1211 participants
		66.67	65.15	64.66
Month 39	Number Analyzed	1183 participants	1140 participants	1201 participants
		68.64	66.40	65.61
Month 42	Number Analyzed	1163 participants	1110 participants	1179 participants
		68.44	69.10	65.82
Month 45	Number Analyzed	1021 participants	970 participants	1023 participants
		67.97	68.66	67.16
Month 48	Number Analyzed	865 participants	806 participants	839 participants
		66.71	63.15	67.58
Month 51	Number Analyzed	698 participants	671 participants	689 participants
		67.77	65.87	67.63
Month 54	Number Analyzed	564 participants	548 participants	550 participants
		64.54	67.88	68.00
Month 57	Number Analyzed	444 participants	445 participants	431 participants
		62.61	65.39	67.98
Month 60	Number Analyzed	327 participants	330 participants	321 participants
		63.00	65.15	65.42
Month 63	Number Analyzed	221 participants	230 participants	223 participants
		62.90	66.52	66.37
Month 66	Number Analyzed	122 participants	131 participants	122 participants
		57.38	67.94	61.48
Month 69	Number Analyzed	46 participants	46 participants	48 participants
		58.70	65.22	66.67
Month 72	Number Analyzed	12 participants	18 participants	15 participants
		50.00	66.67	53.33

20. Secondary Outcome

Title	Percentage of Participants With Disease Activity Score 28-4 (DAS28-4) C-reactive Protein (CRP) <=3.2
Description	DAS28 is a measure of disease activity in participants with rheumatoid arthritis based on a 28-joint assessment. DAS28-4 (CRP) was calculated from number of painful joints out of 28 joints (TJC28) and number of swollen joints out of 28 joints (SJC28), CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicated worse health condition). Total DAS28-4 (CRP) score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (CRP) <= 3.2 indicates low disease activity and > 3.2 to <=5.1 indicates moderate disease activity, >5.1 indicates high disease activity, and DAS28-4 (CRP) < 2.6 indicates remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96.
Time Frame	Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

Outcome Measure Data

Analysis Population Description

FAS included all participants randomized in the study and received at least one dose of investigational drug. Analyses included the data while the participants were receiving the study drug. Here, 'Number Analyzed' signifies number of participants evaluable for each specified time point. LOCF was applied for missing components, and then composite binary outcome was calculated. The percentages were calculated using the numbers of participants evaluable at each visit as the denominators.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1455	1456	1451
Measure Type: Number; Unit of Measure: percentage of participants
Month 2	Number Analyzed	1347 participants	1327 participants	1354 participants
		31.55	35.57	28.36
Month 3	Number Analyzed	1430 participants	1418 participants	1420 participants
		41.68	46.05	37.54
Month 6	Number Analyzed	1416 participants	1396 participants	1406 participants
		50.28	54.87	44.88
Month 9	Number Analyzed	1392 participants	1349 participants	1381 participants
		56.11	59.01	50.91
Month 12	Number Analyzed	1372 participants	1332 participants	1359 participants
		57.73	60.06	53.05
Month 15	Number Analyzed	1353 participants	1311 participants	1341 participants
		60.38	63.54	55.03
Month 18	Number Analyzed	1322 participants	1284 participants	1316 participants
		61.72	63.86	58.51
Month 21	Number Analyzed	1302 participants	1255 participants	1294 participants
		62.29	63.67	59.27
Month 24	Number Analyzed	1287 participants	1226 participants	1273 participants
		61.93	64.11	59.78
Month 27	Number Analyzed	1269 participants	1211 participants	1255 participants
		64.22	67.63	60.56
Month 30	Number Analyzed	1248 participants	1191 participants	1237 participants
		64.66	65.49	63.22
Month 33	Number Analyzed	1232 participants	1177 participants	1221 participants
		63.80	66.02	62.82
Month 36	Number Analyzed	1206 participants	1162 participants	1211 participants
		64.43	64.63	62.59
Month 39	Number Analyzed	1183 participants	1140 participants	1201 participants
		65.85	65.18	63.53
Month 42	Number Analyzed	1163 participants	1110 participants	1179 participants
		65.43	67.93	65.31
Month 45	Number Analyzed	1021 participants	970 participants	1023 participants
		64.74	65.77	64.52
Month 48	Number Analyzed	865 participants	806 participants	839 participants
		64.39	64.52	64.36
Month 51	Number Analyzed	698 participants	671 participants	689 participants
		65.19	66.47	65.46
Month 54	Number Analyzed	564 participants	548 participants	550 participants
		64.18	66.24	66.55
Month 57	Number Analyzed	444 participants	445 participants	431 participants
		63.06	63.60	67.29
Month 60	Number Analyzed	327 participants	330 participants	321 participants
		62.69	64.24	65.11
Month 63	Number Analyzed	221 participants	230 participants	223 participants
		60.18	64.35	68.61
Month 66	Number Analyzed	122 participants	131 participants	122 participants
		55.74	66.41	60.66
Month 69	Number Analyzed	46 participants	46 participants	48 participants
		58.70	56.52	70.83
Month 72	Number Analyzed	12 participants	18 participants	15 participants
		50.00	61.11	73.33

21. Secondary Outcome

Title	Number of Participants With an American College of Rheumatology 20 Percent (%) (ACR20) Response
Description	ACR20 response is a >= 20% improvement in TJC (28) and SJC (28) and >=20% improvement in 3 of the 5 remaining ACR-core criteria: 1) PGA of arthritis, 2) PtGA of arthritis, 3) participant's assessment of arthritis pain, 4) participant's assessment of functional disability by HAQ-DI, and 5) CRP (mg/L) at each visit. PGA: physician's global assessment of arthritis on VAS, 0 (very well) to 100 mm (worst arthritis), higher scores=worse condition. PtGA: participant's global assessment of arthritis on VAS, 0 mm (very well) to 100 mm (worst arthritis condition), higher scores = worse condition. Participant's assessment of arthritis pain: assessed on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (unable to do), higher score=more disability.
Time Frame	Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

Outcome Measure Data

Analysis Population Description

FAS included all participants randomized in the study and received at least one dose of investigational drug. Analyses included the data while the participants were receiving the study drug. Here, 'Number Analyzed' signifies number of participants evaluable for each specified time point. LOCF was applied for missing components, and then composite binary outcome was calculated.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1455	1456	1451
Measure Type: Count of Participants; Unit of Measure: Participants
Month 2	Number Analyzed	1335 participants	1316 participants	1337 participants
		832 62.3%	867 65.9%	812 60.7%
Month 3	Number Analyzed	1418 participants	1398 participants	1396 participants
		979 69.0%	992 71.0%	923 66.1%
Month 6	Number Analyzed	1402 participants	1375 participants	1382 participants
		999 71.3%	1012 73.6%	981 71.0%
Month 9	Number Analyzed	1375 participants	1328 participants	1356 participants
		1019 74.1%	1004 75.6%	987 72.8%
Month 12	Number Analyzed	1362 participants	1308 participants	1333 participants
		1033 75.8%	992 75.8%	966 72.5%
Month 15	Number Analyzed	1341 participants	1291 participants	1315 participants
		1017 75.8%	1003 77.7%	969 73.7%
Month 18	Number Analyzed	1309 participants	1266 participants	1289 participants
		981 74.9%	974 76.9%	937 72.7%
Month 21	Number Analyzed	1289 participants	1238 participants	1271 participants
		955 74.1%	953 77.0%	949 74.7%
Month 24	Number Analyzed	1275 participants	1209 participants	1251 participants
		956 75.0%	922 76.3%	922 73.7%
Month 27	Number Analyzed	1255 participants	1190 participants	1234 participants
		961 76.6%	917 77.1%	913 74.0%
Month 30	Number Analyzed	1237 participants	1173 participants	1213 participants
		932 75.3%	899 76.6%	931 76.8%
Month 33	Number Analyzed	1220 participants	1157 participants	1194 participants
		935 76.6%	888 76.8%	922 77.2%
Month 36	Number Analyzed	1193 participants	1145 participants	1189 participants
		907 76.0%	881 76.9%	887 74.6%
Month 39	Number Analyzed	1172 participants	1122 participants	1180 participants
		896 76.5%	843 75.1%	887 75.2%
Month 42	Number Analyzed	1153 participants	1091 participants	1154 participants
		905 78.5%	848 77.7%	883 76.5%
Month 45	Number Analyzed	1010 participants	955 participants	1006 participants
		780 77.2%	718 75.2%	790 78.5%
Month 48	Number Analyzed	854 participants	795 participants	821 participants
		654 76.6%	587 73.8%	639 77.8%
Month 51	Number Analyzed	691 participants	659 participants	675 participants
		535 77.4%	485 73.6%	518 76.7%
Month 54	Number Analyzed	559 participants	536 participants	538 participants
		434 77.6%	396 73.9%	400 74.3%
Month 57	Number Analyzed	441 participants	436 participants	421 participants
		337 76.4%	321 73.6%	302 71.7%
Month 60	Number Analyzed	323 participants	323 participants	314 participants
		243 75.2%	237 73.4%	232 73.9%
Month 63	Number Analyzed	217 participants	221 participants	220 participants
		163 75.1%	166 75.1%	161 73.2%
Month 66	Number Analyzed	119 participants	130 participants	122 participants
		85 71.4%	101 77.7%	89 73.0%
Month 69	Number Analyzed	46 participants	46 participants	48 participants
		26 56.5%	36 78.3%	37 77.1%
Month 72	Number Analyzed	11 participants	18 participants	15 participants
		5 45.5%	15 83.3%	10 66.7%

22. Secondary Outcome

Title	Number of Participants With an American College of Rheumatology 50% (ACR50) Response
Description	ACR50 response is a >= 50% improvement in TJC (28) and SJC (28) and >=50% improvement in 3 of the 5 remaining ACR-core criteria: 1) PGA of arthritis, 2) PtGA of arthritis, 3) participant's assessment of arthritis pain, 4) participant's assessment of functional disability by HAQ-DI, and 5) CRP (mg/L) at each visit. PGA: physician's global assessment of arthritis on VAS, 0 (very well) to 100 mm (worst arthritis), higher scores=worse condition. PtGA: participant's global assessment of arthritis on VAS, 0 mm (very well) to 100 mm (worst arthritis condition), higher scores = worse condition. Participant's assessment of arthritis pain: assessed on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (unable to do), higher score=more disability.
Time Frame	Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

Outcome Measure Data

Analysis Population Description

FAS included all participants randomized in the study and received at least one dose of investigational drug. Analyses included the data while the participants were receiving the study drug. Here, 'Number Analyzed' signifies number of participants evaluable for each specified time point. LOCF was applied for missing components, and then composite binary outcome was calculated.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1455	1456	1451
Measure Type: Count of Participants; Unit of Measure: Participants
Month 2	Number Analyzed	1337 participants	1321 participants	1346 participants
		402 30.1%	452 34.2%	336 25.0%
Month 3	Number Analyzed	1422 participants	1405 participants	1404 participants
		528 37.1%	561 39.9%	460 32.8%
Month 6	Number Analyzed	1408 participants	1378 participants	1387 participants
		605 43.0%	614 44.6%	533 38.4%
Month 9	Number Analyzed	1381 participants	1333 participants	1356 participants
		620 44.9%	651 48.8%	577 42.6%
Month 12	Number Analyzed	1362 participants	1312 participants	1334 participants
		631 46.3%	654 49.8%	577 43.3%
Month 15	Number Analyzed	1340 participants	1290 participants	1313 participants
		652 48.7%	668 51.8%	582 44.3%
Month 18	Number Analyzed	1312 participants	1265 participants	1290 participants
		633 48.2%	643 50.8%	609 47.2%
Month 21	Number Analyzed	1290 participants	1234 participants	1272 participants
		607 47.1%	623 50.5%	608 47.8%
Month 24	Number Analyzed	1276 participants	1209 participants	1249 participants
		622 48.7%	616 51.0%	592 47.4%
Month 27	Number Analyzed	1258 participants	1194 participants	1231 participants
		620 49.3%	602 50.4%	596 48.4%
Month 30	Number Analyzed	1236 participants	1177 participants	1213 participants
		599 48.5%	609 51.7%	610 50.3%
Month 33	Number Analyzed	1220 participants	1158 participants	1200 participants
		585 48.0%	611 52.8%	594 49.5%
Month 36	Number Analyzed	1195 participants	1143 participants	1188 participants
		603 50.5%	566 49.5%	592 49.8%
Month 39	Number Analyzed	1170 participants	1121 participants	1179 participants
		595 50.9%	588 52.5%	561 47.6%
Month 42	Number Analyzed	1151 participants	1093 participants	1161 participants
		592 51.4%	578 52.9%	587 50.6%
Month 45	Number Analyzed	1011 participants	955 participants	1008 participants
		521 51.5%	481 50.4%	519 51.5%
Month 48	Number Analyzed	854 participants	794 participants	826 participants
		422 49.4%	385 48.5%	424 51.3%
Month 51	Number Analyzed	693 participants	659 participants	677 participants
		350 50.5%	320 48.6%	346 51.1%
Month 54	Number Analyzed	560 participants	538 participants	540 participants
		284 50.7%	271 50.4%	268 49.6%
Month 57	Number Analyzed	440 participants	437 participants	422 participants
		200 45.5%	210 48.1%	209 49.5%
Month 60	Number Analyzed	325 participants	322 participants	314 participants
		152 46.8%	151 46.9%	150 47.8%
Month 63	Number Analyzed	220 participants	223 participants	219 participants
		100 45.5%	104 46.6%	103 47.0%
Month 66	Number Analyzed	122 participants	129 participants	121 participants
		52 42.6%	68 52.7%	55 45.5%
Month 69	Number Analyzed	45 participants	45 participants	47 participants
		16 35.6%	20 44.4%	27 57.4%
Month 72	Number Analyzed	11 participants	18 participants	15 participants
		3 27.3%	6 33.3%	7 46.7%

23. Secondary Outcome

Title	Number of Participants With an American College of Rheumatology 70% (ACR70) Response
Description	ACR70 response is a >= 70% improvement in TJC (28) and SJC (28) and >=70% improvement in 3 of the 5 remaining ACR-core criteria: 1) PGA of arthritis, 2) PtGA of arthritis, 3) participant's assessment of arthritis pain, 4) participant's assessment of functional disability by HAQ-DI, and 5) CRP (mg/L) at each visit. PGA: physician's global assessment of arthritis on VAS, 0 (very well) to 100 mm (worst arthritis), higher scores=worse condition. PtGA: participant's global assessment of arthritis on VAS, 0 mm (very well) to 100 mm (worst arthritis condition), higher scores = worse condition. Participant's assessment of arthritis pain: assessed on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (unable to do), higher score=more disability.
Time Frame	Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72

Outcome Measure Data

Analysis Population Description

FAS included all participants randomized in the study and received at least one dose of investigational drug. Analyses included the data while the participants were receiving the study drug. Here, 'Number Analyzed' signifies number of participants evaluable for each specified time point. LOCF was applied for missing components, and then composite binary outcome was calculated.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1455	1456	1451
Measure Type: Count of Participants; Unit of Measure: Participants
Month 2	Number Analyzed	1343 participants	1326 participants	1354 participants
		152 11.3%	193 14.6%	113 8.3%
Month 3	Number Analyzed	1425 participants	1414 participants	1413 participants
		253 17.8%	268 19.0%	199 14.1%
Month 6	Number Analyzed	1409 participants	1388 participants	1397 participants
		282 20.0%	331 23.8%	234 16.8%
Month 9	Number Analyzed	1383 participants	1336 participants	1366 participants
		328 23.7%	367 27.5%	291 21.3%
Month 12	Number Analyzed	1364 participants	1312 participants	1338 participants
		337 24.7%	373 28.4%	284 21.2%
Month 15	Number Analyzed	1342 participants	1294 participants	1323 participants
		359 26.8%	390 30.1%	304 23.0%
Month 18	Number Analyzed	1311 participants	1269 participants	1295 participants
		358 27.3%	382 30.1%	325 25.1%
Month 21	Number Analyzed	1293 participants	1238 participants	1277 participants
		362 28.0%	370 29.9%	322 25.2%
Month 24	Number Analyzed	1279 participants	1211 participants	1255 participants
		349 27.3%	386 31.9%	328 26.1%
Month 27	Number Analyzed	1259 participants	1192 participants	1238 participants
		374 29.7%	390 32.7%	342 27.6%
Month 30	Number Analyzed	1238 participants	1177 participants	1221 participants
		369 29.8%	397 33.7%	358 29.3%
Month 33	Number Analyzed	1222 participants	1160 participants	1204 participants
		357 29.2%	392 33.8%	355 29.5%
Month 36	Number Analyzed	1195 participants	1145 participants	1193 participants
		362 30.3%	343 30.0%	351 29.4%
Month 39	Number Analyzed	1173 participants	1125 participants	1186 participants
		371 31.6%	361 32.1%	338 28.5%
Month 42	Number Analyzed	1152 participants	1098 participants	1163 participants
		376 32.6%	342 31.1%	343 29.5%
Month 45	Number Analyzed	1010 participants	957 participants	1006 participants
		313 31.0%	298 31.1%	298 29.6%
Month 48	Number Analyzed	855 participants	794 participants	826 participants
		256 29.9%	228 28.7%	238 28.8%
Month 51	Number Analyzed	691 participants	657 participants	677 participants
		216 31.3%	195 29.7%	199 29.4%
Month 54	Number Analyzed	559 participants	538 participants	538 participants
		159 28.4%	163 30.3%	160 29.7%
Month 57	Number Analyzed	441 participants	438 participants	421 participants
		128 29.0%	127 29.0%	118 28.0%
Month 60	Number Analyzed	326 participants	321 participants	315 participants
		79 24.2%	83 25.9%	92 29.2%
Month 63	Number Analyzed	220 participants	223 participants	219 participants
		58 26.4%	57 25.6%	64 29.2%
Month 66	Number Analyzed	122 participants	130 participants	122 participants
		25 20.5%	38 29.2%	35 28.7%
Month 69	Number Analyzed	46 participants	45 participants	48 participants
		8 17.4%	15 33.3%	14 29.2%
Month 72	Number Analyzed	11 participants	18 participants	15 participants
		2 18.2%	5 27.8%	4 26.7%

24. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Months 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63
Description	HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.
Time Frame	Baseline, Months 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

Outcome Measure Data

Analysis Population Description

FAS: all participants randomized and received at least one dose of drug. Mixed model for repeated measures used without imputation for missing values. Analyses included data while participants were receiving drug. Only visits with N > 50 participants in each treatment group included in analyses. Number of Participants Analyzed: number of participants included in mixed model for repeated measures. Number Analyzed: number of participants evaluable for each specified time point.

Arm/Group Title		Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description:		Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
Overall Number of Participants Analyzed		1409	1390	1388
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Change at Month 2	Number Analyzed	1325 participants	1301 participants	1323 participants
		-0.42 (0.02)	-0.45 (0.02)	-0.38 (0.02)
Change at Month 3	Number Analyzed	1371 participants	1329 participants	1320 participants
		-0.45 (0.02)	-0.48 (0.02)	-0.42 (0.02)
Change at Month 6	Number Analyzed	1341 participants	1297 participants	1299 participants
		-0.50 (0.02)	-0.51 (0.02)	-0.46 (0.02)
Change at Month 9	Number Analyzed	1287 participants	1247 participants	1248 participants
		-0.51 (0.02)	-0.55 (0.02)	-0.47 (0.02)
Change at Month 12	Number Analyzed	1256 participants	1205 participants	1200 participants
		-0.52 (0.02)	-0.53 (0.02)	-0.49 (0.02)
Change at Month 15	Number Analyzed	1223 participants	1171 participants	1179 participants
		-0.53 (0.02)	-0.56 (0.02)	-0.51 (0.02)
Change at Month 18	Number Analyzed	1189 participants	1122 participants	1143 participants
		-0.52 (0.02)	-0.56 (0.02)	-0.49 (0.02)
Change at Month 21	Number Analyzed	1172 participants	1076 participants	1118 participants
		-0.53 (0.02)	-0.55 (0.02)	-0.50 (0.02)
Change at Month 24	Number Analyzed	1135 participants	1052 participants	1101 participants
		-0.52 (0.02)	-0.57 (0.02)	-0.49 (0.02)
Change at Month 27	Number Analyzed	1102 participants	1015 participants	1054 participants
		-0.52 (0.02)	-0.56 (0.02)	-0.51 (0.02)
Change at Month 30	Number Analyzed	1078 participants	998 participants	1045 participants
		-0.53 (0.02)	-0.55 (0.02)	-0.50 (0.02)
Change at Month 33	Number Analyzed	1063 participants	977 participants	1041 participants
		-0.51 (0.02)	-0.56 (0.02)	-0.52 (0.02)
Change at Month 36	Number Analyzed	1034 participants	953 participants	1020 participants
		-0.50 (0.02)	-0.54 (0.02)	-0.48 (0.02)
Change at Month 39	Number Analyzed	989 participants	892 participants	964 participants
		-0.51 (0.02)	-0.54 (0.02)	-0.49 (0.02)
Change at Month 42	Number Analyzed	854 participants	770 participants	833 participants
		-0.51 (0.02)	-0.52 (0.02)	-0.50 (0.02)
Change at Month 45	Number Analyzed	713 participants	642 participants	678 participants
		-0.50 (0.02)	-0.51 (0.02)	-0.51 (0.02)
Change at Month 48	Number Analyzed	569 participants	509 participants	539 participants
		-0.50 (0.02)	-0.50 (0.02)	-0.48 (0.02)
Change at Month 51	Number Analyzed	461 participants	420 participants	416 participants
		-0.53 (0.02)	-0.49 (0.02)	-0.50 (0.02)
Change at Month 54	Number Analyzed	364 participants	330 participants	324 participants
		-0.53 (0.02)	-0.51 (0.02)	-0.48 (0.02)
Change at Month 57	Number Analyzed	266 participants	240 participants	247 participants
		-0.49 (0.02)	-0.48 (0.02)	-0.48 (0.02)
Change at Month 60	Number Analyzed	185 participants	181 participants	167 participants
		-0.52 (0.03)	-0.49 (0.03)	-0.48 (0.03)
Change at Month 63	Number Analyzed	107 participants	108 participants	96 participants
		-0.54 (0.03)	-0.48 (0.03)	-0.48 (0.04)

Adverse Events

Time Frame	Baseline up to last contact date (maximum up to 72 months)
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. SAS included all participants randomized in the study and received at least one dose of the randomized investigational drug. Total 153 deaths of which 152 were adjudicated and 1 occurred after the participant discontinued from the study.
Arm/Group Title	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
Arm/Group Description	Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.	Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.	In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.
All-Cause Mortality
	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	49/1455 (3.37%)	66/1456 (4.53%)	38/1451 (2.62%)
Serious Adverse Events
	Tofacitinib 5 mg BID	Tofacitinib 10 mg BID	TNFi
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	373/1455 (25.64%)	420/1456 (28.85%)	339/1451 (23.36%)
Blood and lymphatic system disorders
Agranulocytosis * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Anaemia * 1	9/1455 (0.62%)	4/1456 (0.27%)	1/1451 (0.07%)
Blood loss anaemia * 1	1/1455 (0.07%)	0/1456 (0.00%)	1/1451 (0.07%)
Cytopenia * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Disseminated intravascular coagulation * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Haemolytic anaemia * 1	1/1455 (0.07%)	1/1456 (0.07%)	0/1451 (0.00%)
Iron deficiency anaemia * 1	2/1455 (0.14%)	0/1456 (0.00%)	1/1451 (0.07%)
Leukocytosis * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Leukopenia * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Lymphadenopathy * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Neutropenia * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Pancytopenia * 1	2/1455 (0.14%)	1/1456 (0.07%)	4/1451 (0.28%)
Cardiac disorders
Acute coronary syndrome * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Acute left ventricular failure * 1	1/1455 (0.07%)	1/1456 (0.07%)	0/1451 (0.00%)
Angina pectoris * 1	4/1455 (0.27%)	2/1456 (0.14%)	3/1451 (0.21%)
Angina unstable * 1	3/1455 (0.21%)	3/1456 (0.21%)	3/1451 (0.21%)
Aortic valve disease * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Arrhythmia * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Arrhythmia supraventricular * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Atrial fibrillation * 1	7/1455 (0.48%)	8/1456 (0.55%)	6/1451 (0.41%)
Atrial flutter * 1	2/1455 (0.14%)	1/1456 (0.07%)	1/1451 (0.07%)
Atrioventricular block * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Cardiac arrest * 1	0/1455 (0.00%)	4/1456 (0.27%)	0/1451 (0.00%)
Cardiac failure * 1	2/1455 (0.14%)	3/1456 (0.21%)	3/1451 (0.21%)
Cardiac failure acute * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Cardiac failure chronic * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Cardiac failure congestive * 1	1/1455 (0.07%)	6/1456 (0.41%)	0/1451 (0.00%)
Cardiac pseudoaneurysm * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Cardio-respiratory arrest * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Cardiomyopathy * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Cardiovascular insufficiency * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Chronic left ventricular failure * 1	1/1455 (0.07%)	0/1456 (0.00%)	1/1451 (0.07%)
Congestive cardiomyopathy * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Coronary artery disease * 1	8/1455 (0.55%)	3/1456 (0.21%)	1/1451 (0.07%)
Coronary artery insufficiency * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Coronary artery occlusion * 1	0/1455 (0.00%)	1/1456 (0.07%)	1/1451 (0.07%)
Coronary artery stenosis * 1	2/1455 (0.14%)	0/1456 (0.00%)	1/1451 (0.07%)
Diastolic dysfunction * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Ischaemic cardiomyopathy * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Mitral valve disease * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Myocardial infarction * 1	0/1455 (0.00%)	1/1456 (0.07%)	4/1451 (0.28%)
Myocardial ischaemia * 1	4/1455 (0.27%)	3/1456 (0.21%)	0/1451 (0.00%)
Pericarditis * 1	1/1455 (0.07%)	0/1456 (0.00%)	3/1451 (0.21%)
Right ventricular dysfunction * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Sinus node dysfunction * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Supraventricular tachycardia * 1	0/1455 (0.00%)	3/1456 (0.21%)	0/1451 (0.00%)
Ventricular fibrillation * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Ventricular tachycardia * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Congenital, familial and genetic disorders
Corneal dystrophy * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Developmental hip dysplasia * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Exomphalos * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Hydrocele * 1	0/1455 (0.00%)	1/1456 (0.07%)	1/1451 (0.07%)
Ear and labyrinth disorders
Acute vestibular syndrome * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Meniere's disease * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Vertigo * 1	1/1455 (0.07%)	2/1456 (0.14%)	1/1451 (0.07%)
Vestibular disorder * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Endocrine disorders
Adrenal disorder * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Adrenal haematoma * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Hyperthyroidism * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Thyroid mass * 1	0/1455 (0.00%)	0/1456 (0.00%)	2/1451 (0.14%)
Eye disorders
Cataract * 1	3/1455 (0.21%)	6/1456 (0.41%)	3/1451 (0.21%)
Diabetic retinopathy * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Episcleritis * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Keratoconus * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Macular hole * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Necrotising retinitis * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Retinal detachment * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Retinal vasculitis * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Ulcerative keratitis * 1	1/1455 (0.07%)	1/1456 (0.07%)	0/1451 (0.00%)
Uveitis * 1	0/1455 (0.00%)	1/1456 (0.07%)	1/1451 (0.07%)
Gastrointestinal disorders
Abdominal compartment syndrome * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Abdominal discomfort * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Abdominal distension * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Abdominal hernia * 1	1/1455 (0.07%)	1/1456 (0.07%)	0/1451 (0.00%)
Abdominal incarcerated hernia * 1	1/1455 (0.07%)	0/1456 (0.00%)	1/1451 (0.07%)
Abdominal pain * 1	5/1455 (0.34%)	1/1456 (0.07%)	2/1451 (0.14%)
Abdominal pain upper * 1	1/1455 (0.07%)	0/1456 (0.00%)	1/1451 (0.07%)
Ascites * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Chronic gastritis * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Colitis * 1	4/1455 (0.27%)	0/1456 (0.00%)	0/1451 (0.00%)
Colitis ischaemic * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Constipation * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Diarrhoea * 1	4/1455 (0.27%)	2/1456 (0.14%)	1/1451 (0.07%)
Diverticular perforation * 1	0/1455 (0.00%)	1/1456 (0.07%)	1/1451 (0.07%)
Duodenal stenosis * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Duodenal ulcer haemorrhage * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Dysphagia * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Enteritis * 1	1/1455 (0.07%)	1/1456 (0.07%)	0/1451 (0.00%)
Enterocolitis * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Faecaloma * 1	1/1455 (0.07%)	0/1456 (0.00%)	1/1451 (0.07%)
Gastric polyps * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Gastric ulcer * 1	2/1455 (0.14%)	0/1456 (0.00%)	1/1451 (0.07%)
Gastric ulcer haemorrhage * 1	1/1455 (0.07%)	0/1456 (0.00%)	1/1451 (0.07%)
Gastritis * 1	3/1455 (0.21%)	1/1456 (0.07%)	2/1451 (0.14%)
Gastritis erosive * 1	1/1455 (0.07%)	1/1456 (0.07%)	0/1451 (0.00%)
Gastritis haemorrhagic * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Gastrointestinal erosion * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Gastrointestinal haemorrhage * 1	1/1455 (0.07%)	1/1456 (0.07%)	4/1451 (0.28%)
Gastrointestinal inflammation * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Gastrooesophageal reflux disease * 1	1/1455 (0.07%)	1/1456 (0.07%)	1/1451 (0.07%)
Haematochezia * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Hiatus hernia * 1	1/1455 (0.07%)	0/1456 (0.00%)	2/1451 (0.14%)
Ileus * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Impaired gastric emptying * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Inguinal hernia * 1	2/1455 (0.14%)	3/1456 (0.21%)	3/1451 (0.21%)
Intestinal ischaemia * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Intestinal obstruction * 1	1/1455 (0.07%)	1/1456 (0.07%)	1/1451 (0.07%)
Irritable bowel syndrome * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Ischaemic enteritis * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Jejunal ulcer * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Jejunal ulcer perforation * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Large intestinal ulcer * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Large intestine perforation * 1	1/1455 (0.07%)	1/1456 (0.07%)	0/1451 (0.00%)
Mallory-Weiss syndrome * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Melaena * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Mesenteric vein thrombosis * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Nausea * 1	3/1455 (0.21%)	0/1456 (0.00%)	1/1451 (0.07%)
Obstruction gastric * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Obstructive pancreatitis * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Obturator hernia * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Oesophageal food impaction * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Oesophagitis * 1	1/1455 (0.07%)	0/1456 (0.00%)	1/1451 (0.07%)
Pancreatitis * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Pancreatitis acute * 1	1/1455 (0.07%)	2/1456 (0.14%)	2/1451 (0.14%)
Pancreatitis chronic * 1	0/1455 (0.00%)	2/1456 (0.14%)	0/1451 (0.00%)
Pancreatitis haemorrhagic * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Peptic ulcer * 1	1/1455 (0.07%)	0/1456 (0.00%)	1/1451 (0.07%)
Peptic ulcer haemorrhage * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Peptic ulcer perforation * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Rectal haemorrhage * 1	0/1455 (0.00%)	1/1456 (0.07%)	1/1451 (0.07%)
Small intestinal obstruction * 1	3/1455 (0.21%)	1/1456 (0.07%)	0/1451 (0.00%)
Small intestinal perforation * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Thrombosis mesenteric vessel * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Umbilical hernia * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Upper gastrointestinal haemorrhage * 1	1/1455 (0.07%)	1/1456 (0.07%)	1/1451 (0.07%)
Vomiting * 1	2/1455 (0.14%)	1/1456 (0.07%)	3/1451 (0.21%)
General disorders
Accidental death * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Adverse drug reaction * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Asthenia * 1	1/1455 (0.07%)	1/1456 (0.07%)	1/1451 (0.07%)
Chest discomfort * 1	3/1455 (0.21%)	0/1456 (0.00%)	1/1451 (0.07%)
Chest pain * 1	0/1455 (0.00%)	1/1456 (0.07%)	1/1451 (0.07%)
Complication associated with device * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Death * 1	1/1455 (0.07%)	2/1456 (0.14%)	4/1451 (0.28%)
Device intolerance * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Drug intolerance * 1	0/1455 (0.00%)	1/1456 (0.07%)	1/1451 (0.07%)
Impaired healing * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Inflammation * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Mucosal inflammation * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Multiple organ dysfunction syndrome * 1	1/1455 (0.07%)	1/1456 (0.07%)	1/1451 (0.07%)
Non-cardiac chest pain * 1	4/1455 (0.27%)	5/1456 (0.34%)	5/1451 (0.34%)
Oedema peripheral * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Pyrexia * 1	1/1455 (0.07%)	3/1456 (0.21%)	2/1451 (0.14%)
Sudden death * 1	0/1455 (0.00%)	1/1456 (0.07%)	1/1451 (0.07%)
Systemic inflammatory response syndrome * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Hepatobiliary disorders
Bile duct stone * 1	2/1455 (0.14%)	1/1456 (0.07%)	0/1451 (0.00%)
Biliary colic * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Cholangitis * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Cholecystitis * 1	1/1455 (0.07%)	3/1456 (0.21%)	3/1451 (0.21%)
Cholecystitis acute * 1	3/1455 (0.21%)	2/1456 (0.14%)	1/1451 (0.07%)
Cholecystitis chronic * 1	0/1455 (0.00%)	2/1456 (0.14%)	2/1451 (0.14%)
Cholelithiasis * 1	4/1455 (0.27%)	5/1456 (0.34%)	4/1451 (0.28%)
Cirrhosis alcoholic * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Drug-induced liver injury * 1	0/1455 (0.00%)	0/1456 (0.00%)	2/1451 (0.14%)
Gallbladder obstruction * 1	1/1455 (0.07%)	1/1456 (0.07%)	0/1451 (0.00%)
Gallbladder rupture * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Hepatic cirrhosis * 1	0/1455 (0.00%)	1/1456 (0.07%)	2/1451 (0.14%)
Hepatorenal failure * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Hepatotoxicity * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Hypertransaminasaemia * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Immune system disorders
Anaphylactic reaction * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Anaphylactic shock * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Drug hypersensitivity * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Hypersensitivity * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Infections and infestations
Abscess * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Abscess limb * 1	3/1455 (0.21%)	1/1456 (0.07%)	1/1451 (0.07%)
Acute pulmonary histoplasmosis * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Acute sinusitis * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Adenovirus infection * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Anal abscess * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Appendiceal abscess * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Appendicitis * 1	4/1455 (0.27%)	4/1456 (0.27%)	0/1451 (0.00%)
Appendicitis perforated * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Arthritis bacterial * 1	2/1455 (0.14%)	4/1456 (0.27%)	4/1451 (0.28%)
Arthritis infective * 1	0/1455 (0.00%)	2/1456 (0.14%)	0/1451 (0.00%)
Atypical pneumonia * 1	0/1455 (0.00%)	0/1456 (0.00%)	2/1451 (0.14%)
Bacteraemia * 1	1/1455 (0.07%)	0/1456 (0.00%)	1/1451 (0.07%)
Bacterial infection * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Bacterial sepsis * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Bone tuberculosis * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Brain abscess * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Breast abscess * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Bronchiolitis * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Bronchitis * 1	10/1455 (0.69%)	9/1456 (0.62%)	7/1451 (0.48%)
Bronchitis bacterial * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Bronchitis viral * 1	1/1455 (0.07%)	1/1456 (0.07%)	0/1451 (0.00%)
Bronchopulmonary aspergillosis * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Bursitis infective * 1	0/1455 (0.00%)	0/1456 (0.00%)	2/1451 (0.14%)
COVID-19 * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
COVID-19 pneumonia * 1	1/1455 (0.07%)	5/1456 (0.34%)	1/1451 (0.07%)
Carbuncle * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Cellulitis * 1	12/1455 (0.82%)	13/1456 (0.89%)	15/1451 (1.03%)
Cellulitis staphylococcal * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Cholecystitis infective * 1	1/1455 (0.07%)	1/1456 (0.07%)	1/1451 (0.07%)
Chorioretinitis * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Chronic sinusitis * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Clostridium difficile colitis * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Colonic abscess * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Complicated appendicitis * 1	2/1455 (0.14%)	0/1456 (0.00%)	1/1451 (0.07%)
Cytomegalovirus chorioretinitis * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Cytomegalovirus infection * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Dengue fever * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Device related infection * 1	2/1455 (0.14%)	2/1456 (0.14%)	1/1451 (0.07%)
Diarrhoea infectious * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Disseminated tuberculosis * 1	0/1455 (0.00%)	2/1456 (0.14%)	1/1451 (0.07%)
Disseminated varicella zoster virus infection * 1	0/1455 (0.00%)	4/1456 (0.27%)	0/1451 (0.00%)
Diverticulitis * 1	7/1455 (0.48%)	6/1456 (0.41%)	2/1451 (0.14%)
Encephalitis meningococcal * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Epididymitis * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Erysipelas * 1	1/1455 (0.07%)	0/1456 (0.00%)	1/1451 (0.07%)
Escherichia bacteraemia * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Escherichia infection * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Escherichia pyelonephritis * 1	2/1455 (0.14%)	0/1456 (0.00%)	0/1451 (0.00%)
Escherichia sepsis * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Escherichia urinary tract infection * 1	1/1455 (0.07%)	0/1456 (0.00%)	2/1451 (0.14%)
External ear cellulitis * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Extradural abscess * 1	1/1455 (0.07%)	1/1456 (0.07%)	0/1451 (0.00%)
Eye infection * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Gangrene * 1	0/1455 (0.00%)	1/1456 (0.07%)	1/1451 (0.07%)
Gastroenteritis * 1	4/1455 (0.27%)	7/1456 (0.48%)	3/1451 (0.21%)
Gastroenteritis bacterial * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Gastroenteritis viral * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Gastrointestinal infection * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
H1N1 influenza * 1	0/1455 (0.00%)	2/1456 (0.14%)	0/1451 (0.00%)
Herpes oesophagitis * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Herpes ophthalmic * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Herpes virus infection * 1	1/1455 (0.07%)	0/1456 (0.00%)	0/1451 (0.00%)
Herpes zoster * 1	9/1455 (0.62%)	11/1456 (0.76%)	2/1451 (0.14%)
Histoplasmosis * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Infected bite * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Infection * 1	0/1455 (0.00%)	1/1456 (0.07%)	0/1451 (0.00%)
Infectious pleural effusion * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Influenza * 1	4/1455 (0.27%)	3/1456 (0.21%)	2/1451 (0.14%)
Intervertebral discitis * 1	1/1455 (0.07%)	0/1456 (0.00%)	1/1451 (0.07%)
Joint abscess * 1	0/1455 (0.00%)	0/1456 (0.00%)	1/1451 (0.07%)
Liver abscess * 1	0/1455 (0.00%)	0/1456 (0.00%)