Clinical Trial to Compare Treatment With GP2017 and Humira® in Patients With Rheumatoid Arthritis (ADMYRA)

• ClinicalTrials.gov Identifier: NCT02744755
• Recruitment Status: Completed
• First Posted: April 20, 2016
• Results First Posted: December 19, 2018
• Last Update Posted: December 19, 2018
• Sponsor: Sandoz
• Collaborator: Hexal AG
• Information provided by (Responsible Party): Sandoz

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis
• Interventions: Biological: Adalimumab - GP2017; Biological: Adalimumab - US licensed Humira
• Enrollment: 353

Participant Flow

Recruitment Details	353 patients were randomized (1:1)and received at least one dose of study drug; 303 patients completed the study.Eligible patients in the Humira group who completed Study Period 1 (baseline to week 24) with an at least moderate response by DAS28-CRP score were switched to GP2017 treatment during Study Period 2 (Week 24 to week 48).
Pre-assignment Details	Full analysis set: randomized patients (study drug assigned) Per protocol set study period 1 (SP1) / study period 2(SP2): patients who completed Week 12 (SP1) / Week 48 (SP2) without major protocol deviations and received at least 5 doses of study drug up to Week 10 (SP1) / 10 doses of IMP from Week 24 to Week 46 (SP2)

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Period Title: Study Period 1
Started [1]	177	176
Completed [2]	163	168
Not Completed	14	8
Reason Not Completed
Protocol Violation	2	1
not defined	0	1
Pregnancy	1	0
Adverse Event	1	1
Lost to Follow-up	1	1
Lack of Efficacy	1	0
Withdrawal by Subject	8	4
[1] randomized; [2] completed study period 1
Period Title: Study Period 2
Started	159	166
Completed	145	158
Not Completed	14	8
Reason Not Completed
Adverse Event	5	0
Protocol Violation	1	0
not defined	3	2
Lost to Follow-up	0	2
Withdrawal by Subject	2	2
Lack of Efficacy	3	2

Baseline Characteristics

Arm/Group Title		GP2017	Humira / Switched GP2017	Total
Arm/Group Description		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Total of all reporting groups
Overall Number of Baseline Participants		177	176	353
Baseline Analysis Population Description		Baseline characteristics are presented for Study Period 1 Full Analysis Set (SP 1 FAS ). The SP 1 FAS is comprised of all randomized patients to whom study treatment has been assigned.
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	177 participants	176 participants	353 participants
		52.8 (12.81)	53.8 (12.22)	53.3 (12.51)
		[1] Measure Analysis Population Description: Baseline characteristics are presented for Study Period 1 Full Analysis Set (SP 1 FAS ). The SP 1 FAS is comprised of all randomized patients to whom study treatment has been assigned.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	177 participants	176 participants	353 participants
	Female	153 86.4%	142 80.7%	295 83.6%
	Male	24 13.6%	34 19.3%	58 16.4%
		[1] Measure Analysis Population Description: Baseline characteristics are presented for Study Period 1 Full Analysis Set (SP 1 FAS ). The SP 1 FAS is comprised of all randomized patients to whom study treatment has been assigned.
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	177 participants	176 participants	353 participants
White		152 85.9%	152 86.4%	304 86.1%
American Indian or Alaska Native		14 7.9%	15 8.5%	29 8.2%
Black or African American		6 3.4%	3 1.7%	9 2.5%
Asian		1 0.6%	3 1.7%	4 1.1%
Other		4 2.3%	3 1.7%	7 2.0%
		[1] Measure Analysis Population Description: Baseline characteristics are presented for Study Period 1 Full Analysis Set (SP 1 FAS ). The SP 1 FAS is comprised of all randomized patients to whom study treatment has been assigned.

Outcome Measures

1. Primary Outcome

Title	Study Period 1: Change in DAS28-CRP Score From Baseline at Week 12 in Patients Treated With GP2017 and Patients Treated With Humira
Description	Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity (GDA) or general health (GH), values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value >5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value < 2.6 corresponds to remission DAS28-CRP = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.36 * ln(CRP+1) + 0.014 * GDA or GH + 0.96 where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm
Time Frame	Study period 1: week 12

Outcome Measure Data

Analysis Population Description

Treatment Period 1 Per-Protocol set

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	140	144
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-2.16 (0.114)	-2.18 (0.110)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP2017, Humira / Switched GP2017
	Comments	Therapeutic equivalence in terms of change from baseline in DAS28-CRP at week 12 will be concluded if the 95% confidence interval for the LS mean difference between GP2017 and Humira is contained within the interval [-0.6; 0.6]. A mixed-model repeated measures analysis was performed for DAS28-CRP change from baseline including treatment, stratification factors, time, the interaction between time (visits) and treatment all as categorical variables, and baseline DAS28-CRP as a continuous variable.
	Type of Statistical Test	Equivalence
	Comments	A 0.6 change in DAS28-CRP score is considered as no clinically meaningful difference by EULAR criteria and is therefore used as the equivalence margin limits [0.6,-0.6].
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.24 to 0.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.129
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GP2017, Humira / Switched GP2017
	Comments	Therapeutic equivalence in terms of change from baseline in DAS28-CRP at week 12 will be concluded if the 90% confidence interval for the LS mean difference between GP2017 and Humira is contained within the interval [-0.6; 0.6]. A mixed-model repeated measures analysis was performed for DAS28-CRP change from baseline including treatment, stratification factors, time, the interaction between time (visits) and treatment all as categorical variables, and baseline DAS28-CRP as a continuous variable.
	Type of Statistical Test	Equivalence
	Comments	A 0.6 change in DAS28-CRP score is considered as no clinically meaningful difference by EULAR criteria and is therefore used as the equivalence margin limits [0.6,-0.6].
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 90%; -0.19 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.129
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Study Period 1: Time-weighted Averaged Change From Baseline in DAS28-CRP Until Week 24 in Patients Treated With GP2017 and With Humira
Description	Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity (GDA) or general health (GH), values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value >5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value < 2.6 corresponds to remission DAS28-CRP = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.36 * ln(CRP+1) + 0.014 * GDA or GH + 0.96 where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm
Time Frame	Study period 1: week 24

Outcome Measure Data

Analysis Population Description

Treatment Period 1 Per-Protocol set

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	127	138
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-1.85 (0.098)	-1.93 (0.092)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GP2017, Humira / Switched GP2017
	Comments	ANCOVA model included treatment, body weight as per CRF, prior therapy as per CRF, region as per CRF as fixed effects and baseline DAS28-CRP values as covariate.
	Type of Statistical Test	Equivalence
	Comments	A 0.6 change in DAS28-CRP score is considered as no clinically meaningful difference by EULAR criteria and is therefore used as the equivalence margin limits [0.6,-0.6].
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.096
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GP2017, Humira / Switched GP2017
	Comments	ANCOVA model included treatment, body weight as per CRF, prior therapy as per CRF, region as per CRF as fixed effects and baseline DAS28-CRP values as covariate.
	Type of Statistical Test	Equivalence
	Comments	A 0.6 change in DAS28-CRP score is considered as no clinically meaningful difference by EULAR criteria and is therefore used as the equivalence margin limits [0.6,-0.6].
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 90%; -0.08 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.096
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission
Description	Proportion of patients achieving European League against Rheumatism (EULAR) remission (defined as DAS28 CRP < 2.6 )
Time Frame	week 4, week 12 and week 24

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title		GP2017	Humira / Switched GP2017
Arm/Group Description:		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed		127	138
Measure Type: Count of Participants; Unit of Measure: Participants
EULAR remission week 4	Number Analyzed	123 participants	138 participants
		15 12.2%	7 5.1%
EULAR remission week 12	Number Analyzed	126 participants	138 participants
		32 25.4%	38 27.5%
EULAR remission week 24	Number Analyzed	127 participants	138 participants
		49 38.6%	71 51.4%

4. Secondary Outcome

Title	Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response
Description	Proportion of patients achieving European League against Rheumatism (EULAR) good response (defined as DAS28<=3.2 at post-baseline assessment timepoint(s) with an improvement of >1.2 in DAS28 from baseline.)
Time Frame	week 4, week 12 and week 24

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title		GP2017	Humira / Switched GP2017
Arm/Group Description:		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed		127	138
Measure Type: Count of Participants; Unit of Measure: Participants
Good response week 4	Number Analyzed	123 participants	138 participants
		22 17.9%	25 18.1%
Good response week 12	Number Analyzed	126 participants	138 participants
		51 40.5%	63 45.7%
Good response week 24	Number Analyzed	126 participants	138 participants
		76 60.3%	93 67.4%

5. Secondary Outcome

Title	Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response
Description	Proportion of patients achieving European League against Rheumatism (EULAR) moderate response (defined as DAS28<=3.2 at post-baseline assessment timepoint(s) with an improvement of >0.6 to <=1.2 from baseline or DAS28 >3.2 to <=5.1 with an improvement of >0.6 to <=1.2 or of >1.2 from baseline or DAS28 >5.1 with an improvement of >1.2 from baseline) ;
Time Frame	week 4, week 12 and week 24

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title		GP2017	Humira / Switched GP2017
Arm/Group Description:		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed		127	138
Measure Type: Count of Participants; Unit of Measure: Participants
Moderate response week 4	Number Analyzed	123 participants	138 participants
		63 51.2%	78 56.5%
Moderate response week 12	Number Analyzed	126 participants	138 participants
		64 50.8%	62 44.9%
Moderate response week 24	Number Analyzed	126 participants	138 participants
		42 33.3%	42 30.4%

6. Secondary Outcome

Title	Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria
Description	Proportion of patients achieving EULAR/American College of Rheumatology (EULAR/ACR) Boolean remission criteria (defined as number of tender joint count 28 <=1 and swollen joint count 28 <=1, CRP level (mg/dL) <=1 and patient's global assessment <=1 on a scale of 1-10 (corresponding to <=10 on a scale of 1-100).
Time Frame	week 4, week 12, week 24

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title		GP2017	Humira / Switched GP2017
Arm/Group Description:		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed		127	138
Measure Type: Count of Participants; Unit of Measure: Participants
week 4	Number Analyzed	123 participants	138 participants
		4 3.3%	0 0.0%
week 12	Number Analyzed	126 participants	138 participants
		8 6.3%	12 8.7%
week 24	Number Analyzed	127 participants	138 participants
		19 15.0%	26 18.8%

7. Secondary Outcome

Title	Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira
Description	DAS28-CRP is a disease activity score and defined in primary outcome measure. DAS28-ESR is the DAS28 erythrocyte sedimentation rate score. DAS28-CRP and DAS28-ESR: best is 0,; < 2.6 - remission,; ≥ 2.6 to ≤ 3.2 - low disease activity; > 3.2 to ≤ 5.1 - moderate disease activity; > 5.1 - high disease activity DAS28-ESR = 0.56 * sqrt(tender28) + 0.28*sqrt(swollen28) + 0.7 * ln(ESR) + 0.014 * GDA where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • ESR is erythrocyte sedimentation rate (mm/h) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm.Values range from 0 to 10. Higher values mean a higher disease activity.
Time Frame	study period 1: week 2, 4, 24

Outcome Measure Data

Analysis Population Description

Treatment Period 1 Per-Protocol set

Arm/Group Title		GP2017	Humira / Switched GP2017
Arm/Group Description:		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed		127	138
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
DAS28 CRP week 2	Number Analyzed	122 participants	137 participants
		-0.86 (0.107)	-0.92 (0.101)
DAS28 CRP week 4	Number Analyzed	123 participants	138 participants
		-1.31 (0.112)	-1.36 (0.105)
DAS28 CRP week 24	Number Analyzed	127 participants	138 participants
		-2.61 (0.109)	-2.83 (0.103)
DAS28 ESR week 2	Number Analyzed	125 participants	137 participants
		-0.94 (0.115)	-0.98 (0.109)
DAS28 ESR week 4	Number Analyzed	125 participants	138 participants
		-1.51 (0.124)	-1.51 (0.117)
DAS28 ESR week 24	Number Analyzed	126 participants	138 participants
		-2.97 (0.127)	-3.16 (0.120)

8. Secondary Outcome

Title	Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24
Description	ACR20 response was defined if a patient fulfilled all 3 criteria below: -at least 20% improvement in tender 68 joint count -at least 20% improvement in swollen 66 joint-count; And at least 20% improvement in at least 3 of the following 5 measures: - Patient's assessment of RA pain (visual analogue scale (VAS) 100 mm), -Patient's global assessment of disease activity (VAS 100 mm), -Physician's global assessment of disease activity (VAS 100 mm), -Patient self-assessed disability index(HAQ-DI© score), -Acute phase reactant (CRP or ESR). ACR50 and ACR70 responses were defined as ACR20 response replacing "20% improvement" by "50% improvement" and "70% improvement", respectively.
Time Frame	Week 4, week 12 and week 24

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title		GP2017	Humira / Switched GP2017
Arm/Group Description:		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed		127	138
Measure Type: Count of Participants; Unit of Measure: Participants
ACR20 response Week 4	Number Analyzed	126 participants	138 participants
		64 50.8%	71 51.4%
ACR20 response Week 12	Number Analyzed	127 participants	138 participants
		100 78.7%	106 76.8%
ACR20 response Week 24	Number Analyzed	127 participants	138 participants
		111 87.4%	130 94.2%
ACR50 response Week 4	Number Analyzed	126 participants	138 participants
		25 19.8%	25 18.1%
ACR50 response Week 12	Number Analyzed	127 participants	138 participants
		53 41.7%	67 48.6%
ACR50 response Week 24	Number Analyzed	127 participants	138 participants
		78 61.4%	98 71.0%
ACR70 response Week 4	Number Analyzed	126 participants	138 participants
		7 5.6%	9 6.5%
ACR70 response Week 12	Number Analyzed	127 participants	138 participants
		24 18.9%	35 25.4%
ACR70 response Week 24	Number Analyzed	127 participants	138 participants
		48 37.8%	53 38.4%

9. Secondary Outcome

Title	Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24;
Description	Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst).The HAQ© was scored in accordance with the recommendation from the developers outlined in the "HAQ PACK" from Stanford University, California. Ramey Dr, Fries JF, Singh G. in B. Spilker Quality of Life and Pharmacoleconomics in Clinical Trials, 2nd ed, The Health Assessment Questionnaire 1995 -- Status and Review. Philadelphia: Lippincott-Raven Pub., 1996, p 227 - 237. Fries JF, Spitz P, Kraines G, Holman H. Measurement of Patient Outcome in Arthritis, Arthritis and Rheumatism, 1980, 23:137-145.
Time Frame	Weeks 4, 12 and 24;

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	127	138
Mean (Standard Deviation); Unit of Measure: score on a scale
Week 4	-0.32 (0.519)	-0.32 (0.449)
Week 12	-0.50 (0.576)	-0.47 (0.501)
Week 24	-0.63 (0.610)	-0.59 (0.543)

10. Secondary Outcome

Title	Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24;
Description	Health assessment questionnaire disability index (HAQ-DI©) ranges from 0 (best) to 3 (worst)
Time Frame	Weeks 4, 12 and 24;

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title		GP2017	Humira / Switched GP2017
Arm/Group Description:		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed		127	138
Measure Type: Count of Participants; Unit of Measure: Participants
Week 4	Number Analyzed	125 participants	138 participants
		27 21.6%	33 23.9%
Week 12	Number Analyzed	127 participants	138 participants
		38 29.9%	40 29.0%
Week 24	Number Analyzed	127 participants	138 participants
		46 36.2%	50 36.2%

11. Secondary Outcome

Title	Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24
Description	Health assessment questionnaire (HAQ-DI©) disability index ranges from 0 (best) to 3 (worst)
Time Frame	Weeks 4, 12 and 24;

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title		GP2017	Humira / Switched GP2017
Arm/Group Description:		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed		127	138
Measure Type: Count of Participants; Unit of Measure: Participants
Week 4	Number Analyzed	125 participants	138 participants
		106 84.8%	117 84.8%
Week 12	Number Analyzed	127 participants	138 participants
		102 80.3%	109 79.0%
Week 24	Number Analyzed	127 participants	138 participants
		91 71.7%	106 76.8%

12. Secondary Outcome

Title	Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline)
Description	FACIT© fatigue scale is a 13- item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function, ranging from 0 (worst) to 52 (best).
Time Frame	Weeks 4, 12 and 24;

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	127	138
Mean (Standard Deviation); Unit of Measure: score on a scale
Week 4	6.59 (7.949)	7.25 (8.591)
Week 12	10.49 (9.218)	10.62 (9.134)
Week 24	12.57 (10.760)	12.72 (9.451)

13. Secondary Outcome

Title	Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24
Description	Outcome measure 13 presents changes in CRP measures in blood while Outome measure 7 presents changes in DAS28-CRP scores (calculated composite score to measure the disease activity)
Time Frame	Week 4, week 12, week 24

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	127	138
Mean (Standard Deviation); Unit of Measure: mg/L
CRP change from baseline week 4	-4.79 (8.728)	-4.93 (12.128)
CRP change from baseline week 12	-5.98 (11.270)	-5.07 (11.791)
CRP change from baseline week 24	-2.51 (19.176)	-5.30 (13.726)

14. Secondary Outcome

Title	Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24
Description	Outcome measure 13 presents changes in ESR measures in blood while outcome measure 7 presents changes in DAS28-ESR scores (calculated composite score to measure the disease activity)
Time Frame	Week 4, week 12, week 24

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	127	138
Mean (Standard Deviation); Unit of Measure: mm/h
ESR change from baseline week 4	-16.17 (14.693)	-13.98 (15.823)
ESR change from baseline week 12	-17.33 (16.214)	-15.08 (31.150)
ESR change from baseline week 24	-19.60 (20.494)	-20.49 (18.255)

15. Secondary Outcome

Title	Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira
Description	Incidence of injection site reactions in GP2017 and Humira
Time Frame	Treatment Period 1, 24 weeks

Outcome Measure Data

Analysis Population Description

Safety Set

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	177	176
Measure Type: Count of Participants; Unit of Measure: Participants
incidence of injection site reactions	7 4.0%	11 6.3%
injection site reactions MILD	7 4.0%	7 4.0%
injection site reactions MODERATE	0 0.0%	4 2.3%
injection site reactions SEVERE	0 0.0%	0 0.0%
Injection site erythema	2 1.1%	6 3.4%
Injection site pruritus	2 1.1%	3 1.7%
Injection site pain	2 1.1%	1 0.6%
Injection site inflammation	2 1.1%	0 0.0%
Injection site rash	0 0.0%	2 1.1%
Injection site discolouration	0 0.0%	1 0.6%

16. Secondary Outcome

Title	Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients)
Description	Frequency of patients having anti-drug antibody (ADA) during 24 weeks
Time Frame	baseline, week 2, week 4, week 12, week 24

Outcome Measure Data

Analysis Population Description

Safety Set

Arm/Group Title		GP2017	Humira / Switched GP2017
Arm/Group Description:		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed		177	176
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline	Number Analyzed	176 participants	174 participants
		10 5.7%	6 3.4%
Week 2	Number Analyzed	160 participants	166 participants
		12 7.5%	10 6.0%
Week 4	Number Analyzed	159 participants	166 participants
		14 8.8%	22 13.3%
Week 12	Number Analyzed	157 participants	164 participants
		16 10.2%	23 14.0%
Week 24	Number Analyzed	151 participants	162 participants
		23 15.2%	25 15.4%

17. Secondary Outcome

Title	Study Period 2 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira (Positive Patients)
Description	Frequency of patients having anti-drug antibody (ADA) during 24 weeks
Time Frame	week 24, week 36, week 48

Outcome Measure Data

Analysis Population Description

Safety Set

Arm/Group Title		GP2017	Humira / Switched GP2017
Arm/Group Description:		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed		159	166
Measure Type: Count of Participants; Unit of Measure: Participants
Week 24	Number Analyzed	148 participants	160 participants
		22 14.9%	25 15.6%
Week 36	Number Analyzed	140 participants	153 participants
		21 15.0%	22 14.4%
Week 48	Number Analyzed	113 participants	127 participants
		12 10.6%	12 9.4%

18. Secondary Outcome

Title	Study Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Week 48, in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira
Description	[Not Specified]
Time Frame	week 48

Outcome Measure Data

Analysis Population Description

Treatment period 2 per protocol set. Patients with data available

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	108	126
Measure Type: Count of Participants; Unit of Measure: Participants
ACR20 response Week 48	93 86.1%	111 88.1%
ACR50 response Week 48	72 66.7%	81 64.3%
ACR70 response Week 48	49 45.4%	55 43.7%

19. Secondary Outcome

Title	Study Period 2 - Health Assessment Questionnaire-Disability Index (HAQ-DI©) Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira
Description	Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst)
Time Frame	Weeks 48

Outcome Measure Data

Analysis Population Description

Treatment period 1 per protocol set. Patients with data available

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	108	126
Mean (Standard Deviation); Unit of Measure: score on a scale
	0.01 (0.358)	-0.03 (0.427)

20. Secondary Outcome

Title	Study Period 2 :Proportion of Patients Treated Continuously With GP2017 and Patients Treated With GP2017 After Switch From Humira Achieving HAQ-DI© Score in Normal Range ≤0.5 at Week 48
Description	[Not Specified]
Time Frame	week 48

Outcome Measure Data

Analysis Population Description

Treatment period 2 per protocol set. Patients with data available

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	108	126
Measure Type: Count of Participants; Unit of Measure: Participants
	45 41.7%	52 41.3%

21. Secondary Outcome

Title	Study Period 2 : Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira
Description	FACIT©: from 0 (worst) to 52 (best), a score of less than 30 indicates severe fatigue
Time Frame	week 48

Outcome Measure Data

Analysis Population Description

Treatment period 2 per protocol set. Patients with data available

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	108	126
Mean (Standard Deviation); Unit of Measure: score on a scale
	-0.65 (7.421)	-0.85 (7.476)

22. Secondary Outcome

Title	Study Period 2: Changes From Week 24 at Week 48 in DAS28-CRP and DAS28-ESR Scores in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira
Description	DAS28-CRP is a disease activity score and defined in primary outcome measure. DAS28-ESR is the DAS28 erythrocyte sedimentation rate score. DAS28-CRP and DAS28-ESR: best is 0,; < 2.6 - remission,; ≥ 2.6 to ≤ 3.2 - low disease activity; > 3.2 to ≤ 5.1 - moderate disease activity; > 5.1 - high disease activity DAS28-ESR = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.7 * ln(ESR) + 0.014 * GDA where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • ESR is erythrocyte sedimentation rate (mm/h) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm.Values range from 0 to 10. Higher values mean a higher disease activity.
Time Frame	week 48

Outcome Measure Data

Analysis Population Description

Treatment period 2 per protocol set. Patients with data available

Arm/Group Title		GP2017	Humira / Switched GP2017
Arm/Group Description:		Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed		108	126
Mean (Standard Deviation); Unit of Measure: score on a scale
DAS28-CRP Week 48, change from week 24	Number Analyzed	107 participants	125 participants
		-0.10 (0.893)	0.00 (0.941)
DAS28-ESR Week 48, change from week 24	Number Analyzed	108 participants	126 participants
		-0.04 (1.015)	0.00 (1.025)

23. Secondary Outcome

Title	Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira
Description	Incidence of injection site reactions
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

Safety Set

Arm/Group Title	GP2017	Humira / Switched GP2017
Arm/Group Description:	Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).	Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2).
Overall Number of Participants Analyzed	159	166
Measure Type: Count of Participants; Unit of Measure: Participants
Number of patients with ISRs	1 0.6%	2 1.2%
Injection site erythema	1 0.6%	2 1.2%
Injection site pruritus	0 0.0%	1 0.6%
injection site reactions MILD	1 0.6%	1 0.6%
injection site reactions MODERATE	0 0.0%	1 0.6%
injection site reactions SEVERE	0 0.0%	0 0.0%

Adverse Events

Time Frame	Each patient was followed up for safety during the whole study treatment duration ( approximately 24 months) , and Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for every single patient, + 30 day safety follow up period after study treatment discontinuation.
Adverse Event Reporting Description	AE additional description
Arm/Group Title	Study Period 1 SP1 SAF GP2017	Study Period 1 SP1 SAF Humira	Study Period 2 SP2 SAF Continued GP2017	Study Period 2 SP2 SAF Humira to GP2017	Entire Study SP1 SAF GP2017	Entire Study SP1 SAF Humira/Switched GP2017
Arm/Group Description	Study Period 1 SP1 SAF GP2017	Study Period 1 SP1 SAF Humira	Study Period 2 SP2 SAF Continued GP2017	Study Period 2 SP2 SAF Humira to GP2017	Entire study SP1 SAF GP2017	Entire study SP1 SAF Humira/Switched GP2017
All-Cause Mortality
	Study Period 1 SP1 SAF GP2017	Study Period 1 SP1 SAF Humira	Study Period 2 SP2 SAF Continued GP2017	Study Period 2 SP2 SAF Humira to GP2017	Entire Study SP1 SAF GP2017	Entire Study SP1 SAF Humira/Switched GP2017
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/177 (0.00%)	0/176 (0.00%)	0/159 (0.00%)	0/166 (0.00%)	0/177 (0.00%)	0/176 (0.00%)
Serious Adverse Events
	Study Period 1 SP1 SAF GP2017	Study Period 1 SP1 SAF Humira	Study Period 2 SP2 SAF Continued GP2017	Study Period 2 SP2 SAF Humira to GP2017	Entire Study SP1 SAF GP2017	Entire Study SP1 SAF Humira/Switched GP2017
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	5/177 (2.82%)	4/176 (2.27%)	4/159 (2.52%)	6/166 (3.61%)	7/177 (3.95%)	10/176 (5.68%)
Cardiac disorders
Angina pectoris † 1	0/177 (0.00%)	0/176 (0.00%)	0/159 (0.00%)	1/166 (0.60%)	0/177 (0.00%)	1/176 (0.57%)
Gastrointestinal disorders
Constipation † 1	1/177 (0.56%)	0/176 (0.00%)	1/159 (0.63%)	0/166 (0.00%)	1/177 (0.56%)	0/176 (0.00%)
Diarrhoea † 1	0/177 (0.00%)	0/176 (0.00%)	0/159 (0.00%)	1/166 (0.60%)	0/177 (0.00%)	1/176 (0.57%)
Pancreatitis acute † 1	0/177 (0.00%)	0/176 (0.00%)	0/159 (0.00%)	1/166 (0.60%)	0/177 (0.00%)	1/176 (0.57%)
Upper gastrointestinal haemorrhage † 1	0/177 (0.00%)	1/176 (0.57%)	0/159 (0.00%)	0/166 (0.00%)	0/177 (0.00%)	1/176 (0.57%)
Hepatobiliary disorders
Cholecystitis † 1	1/177 (0.56%)	0/176 (0.00%)	0/159 (0.00%)	0/166 (0.00%)	1/177 (0.56%)	0/176 (0.00%)
Hepatitis † 1	1/177 (0.56%)	0/176 (0.00%)	0/159 (0.00%)	0/166 (0.00%)	1/177 (0.56%)	0/176 (0.00%)
Infections and infestations
Bronchitis † 1	0/177 (0.00%)	0/176 (0.00%)	0/159 (0.00%)	1/166 (0.60%)	0/177 (0.00%)	1/176 (0.57%)
Diverticulitis † 1	0/177 (0.00%)	0/176 (0.00%)	1/159 (0.63%)	0/166 (0.00%)	1/177 (0.56%)	0/176 (0.00%)
Pneumonia † 1	0/177 (0.00%)	0/176 (0.00%)	0/159 (0.00%)	2/166 (1.20%)	0/177 (0.00%)	2/176 (1.14%)
Pneumonia bacterial † 1	1/177 (0.56%)	0/176 (0.00%)	0/159 (0.00%)	0/166 (0.00%)	1/177 (0.56%)	0/176 (0.00%)
Injury, poisoning and procedural complications
Humerus fracture † 1	0/177 (0.00%)	1/176 (0.57%)	0/159 (0.00%)	0/166 (0.00%)	0/177 (0.00%)	1/176 (0.57%)
Lumbar vertebral fracture † 1	0/177 (0.00%)	0/176 (0.00%)	1/159 (0.63%)	0/166 (0.00%)	1/177 (0.56%)	0/176 (0.00%)
Metabolism and nutrition disorders
Hyponatraemia † 1	0/177 (0.00%)	0/176 (0.00%)	0/159 (0.00%)	1/166 (0.60%)	0/177 (0.00%)	1/176 (0.57%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/177 (0.56%)	0/176 (0.00%)	0/159 (0.00%)	0/166 (0.00%)	1/177 (0.56%)	0/176 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm benign † 1	0/177 (0.00%)	1/176 (0.57%)	0/159 (0.00%)	0/166 (0.00%)	0/177 (0.00%)	1/176 (0.57%)
Uterine leiomyoma † 1	0/177 (0.00%)	1/176 (0.57%)	0/159 (0.00%)	0/166 (0.00%)	0/177 (0.00%)	1/176 (0.57%)
Nervous system disorders
Encephalopathy † 1	0/177 (0.00%)	0/176 (0.00%)	1/159 (0.63%)	0/166 (0.00%)	1/177 (0.56%)	0/176 (0.00%)
Epilepsy † 1	0/177 (0.00%)	1/176 (0.57%)	0/159 (0.00%)	0/166 (0.00%)	0/177 (0.00%)	1/176 (0.57%)
Hemianopia homonymous † 1	0/177 (0.00%)	1/176 (0.57%)	0/159 (0.00%)	0/166 (0.00%)	0/177 (0.00%)	1/176 (0.57%)
Intracranial pressure increased † 1	0/177 (0.00%)	1/176 (0.57%)	0/159 (0.00%)	0/166 (0.00%)	0/177 (0.00%)	1/176 (0.57%)
Reproductive system and breast disorders
Uterine prolapse † 1	0/177 (0.00%)	0/176 (0.00%)	0/159 (0.00%)	1/166 (0.60%)	0/177 (0.00%)	1/176 (0.57%)
1 Term from vocabulary, MedDRA (20.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Study Period 1 SP1 SAF GP2017	Study Period 1 SP1 SAF Humira	Study Period 2 SP2 SAF Continued GP2017	Study Period 2 SP2 SAF Humira to GP2017	Entire Study SP1 SAF GP2017	Entire Study SP1 SAF Humira/Switched GP2017
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	83/177 (46.89%)	74/176 (42.05%)	28/159 (17.61%)	26/166 (15.66%)	94/177 (53.11%)	80/176 (45.45%)
Blood and lymphatic system disorders
Leukopenia † 1	2/177 (1.13%)	0/176 (0.00%)	2/159 (1.26%)	0/166 (0.00%)	4/177 (2.26%)	0/176 (0.00%)
Neutropenia † 1	3/177 (1.69%)	0/176 (0.00%)	2/159 (1.26%)	0/166 (0.00%)	5/177 (2.82%)	0/176 (0.00%)
Gastrointestinal disorders
Diarrhoea † 1	4/177 (2.26%)	7/176 (3.98%)	0/159 (0.00%)	0/166 (0.00%)	4/177 (2.26%)	7/176 (3.98%)
Nausea † 1	5/177 (2.82%)	1/176 (0.57%)	0/159 (0.00%)	0/166 (0.00%)	5/177 (2.82%)	1/176 (0.57%)
General disorders
Fatigue † 1	5/177 (2.82%)	0/176 (0.00%)	0/159 (0.00%)	1/166 (0.60%)	5/177 (2.82%)	1/176 (0.57%)
Injection site erythema † 1	2/177 (1.13%)	6/176 (3.41%)	1/159 (0.63%)	2/166 (1.20%)	3/177 (1.69%)	6/176 (3.41%)
Infections and infestations
Bronchitis † 1	4/177 (2.26%)	8/176 (4.55%)	1/159 (0.63%)	4/166 (2.41%)	4/177 (2.26%)	12/176 (6.82%)
Gastroenteritis † 1	2/177 (1.13%)	4/176 (2.27%)	1/159 (0.63%)	0/166 (0.00%)	3/177 (1.69%)	4/176 (2.27%)
Influenza † 1	3/177 (1.69%)	5/176 (2.84%)	1/159 (0.63%)	0/166 (0.00%)	4/177 (2.26%)	5/176 (2.84%)
Oral herpes † 1	4/177 (2.26%)	3/176 (1.70%)	1/159 (0.63%)	0/166 (0.00%)	5/177 (2.82%)	3/176 (1.70%)
Pharyngitis † 1	9/177 (5.08%)	10/176 (5.68%)	1/159 (0.63%)	3/166 (1.81%)	10/177 (5.65%)	10/176 (5.68%)
Sinusitis † 1	5/177 (2.82%)	3/176 (1.70%)	0/159 (0.00%)	2/166 (1.20%)	5/177 (2.82%)	5/176 (2.84%)
Upper respiratory tract infection † 1	12/177 (6.78%)	7/176 (3.98%)	4/159 (2.52%)	3/166 (1.81%)	14/177 (7.91%)	9/176 (5.11%)
Urinary tract infection † 1	4/177 (2.26%)	6/176 (3.41%)	2/159 (1.26%)	3/166 (1.81%)	6/177 (3.39%)	8/176 (4.55%)
Viral upper respiratory tract infection † 1	26/177 (14.69%)	16/176 (9.09%)	4/159 (2.52%)	4/166 (2.41%)	29/177 (16.38%)	19/176 (10.80%)
Injury, poisoning and procedural complications
Fall † 1	2/177 (1.13%)	3/176 (1.70%)	0/159 (0.00%)	1/166 (0.60%)	2/177 (1.13%)	4/176 (2.27%)
Investigations
Transaminases increased † 1	0/177 (0.00%)	3/176 (1.70%)	1/159 (0.63%)	1/166 (0.60%)	1/177 (0.56%)	4/176 (2.27%)
Metabolism and nutrition disorders
Hypercholesterolaemia † 1	3/177 (1.69%)	3/176 (1.70%)	2/159 (1.26%)	0/166 (0.00%)	5/177 (2.82%)	3/176 (1.70%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	8/177 (4.52%)	0/176 (0.00%)	2/159 (1.26%)	0/166 (0.00%)	10/177 (5.65%)	0/176 (0.00%)
Rheumatoid arthritis † 1	3/177 (1.69%)	1/176 (0.57%)	5/159 (3.14%)	2/166 (1.20%)	6/177 (3.39%)	3/176 (1.70%)
Nervous system disorders
Headache † 1	7/177 (3.95%)	5/176 (2.84%)	2/159 (1.26%)	2/166 (1.20%)	8/177 (4.52%)	7/176 (3.98%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	2/177 (1.13%)	1/176 (0.57%)	3/159 (1.89%)	0/166 (0.00%)	5/177 (2.82%)	1/176 (0.57%)
Skin and subcutaneous tissue disorders
Urticaria † 1	0/177 (0.00%)	3/176 (1.70%)	0/159 (0.00%)	1/166 (0.60%)	0/177 (0.00%)	4/176 (2.27%)
Vascular disorders
Hypertension † 1	5/177 (2.82%)	3/176 (1.70%)	2/159 (1.26%)	1/166 (0.60%)	6/177 (3.39%)	4/176 (2.27%)
1 Term from vocabulary, MedDRA (20.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.

Results Point of Contact

• Name/Title: Sandoz Biopharma Clinical Development - Strategic Planning
• Organization: Hexal AG/Sandoz Inc.
• Phone: 0049(0)80244760
• EMail: biopharma.clinicaltrials@sandoz.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Blauvelt A, Leonardi CL, Gaylis N, Jauch-Lembach J, Balfour A, Lemke L, Hachaichi S, Brueckmann I, Festini T, Wiland P. Treatment with SDZ-ADL, an Adalimumab Biosimilar, in Patients with Rheumatoid Arthritis, Psoriasis, or Psoriatic Arthritis: Results of Patient-Reported Outcome Measures from Two Phase III Studies (ADMYRA and ADACCESS). BioDrugs. 2021 Mar;35(2):229-238. doi: 10.1007/s40259-021-00470-1. Epub 2021 Mar 2.

Huizinga TWJ, Torii Y, Muniz R. Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity. Rheumatol Ther. 2021 Mar;8(1):41-61. doi: 10.1007/s40744-020-00259-8. Epub 2020 Dec 1.

Wiland P, Jeka S, Dokoupilova E, Brandt-Jurgens J, Miranda Limon JM, Cantalejo Moreira M, Cabello RV, Jauch-Lembach J, Thakur A, Haliduola H, Brueckmann I, Gaylis NB. Switching to Biosimilar SDZ-ADL in Patients with Moderate-to-Severe Active Rheumatoid Arthritis: 48-Week Efficacy, Safety and Immunogenicity Results From the Phase III, Randomized, Double-Blind ADMYRA Study. BioDrugs. 2020 Dec;34(6):809-823. doi: 10.1007/s40259-020-00447-6.

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT02744755
• Other Study ID Numbers: GP17-302; 2015-003433-10 ( EudraCT Number )
• First Submitted: April 12, 2016
• First Posted: April 20, 2016
• Results First Submitted: September 21, 2018
• Results First Posted: December 19, 2018
• Last Update Posted: December 19, 2018