A Study of Adalimumab in Japanese Subjects With Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT00870467
• Recruitment Status: Completed
• First Posted: March 27, 2009
• Results First Posted: April 5, 2012
• Last Update Posted: August 7, 2012
• Sponsor: Abbott
• Collaborator: Eisai Co., Ltd.
• Information provided by (Responsible Party): Abbott

• 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: Double-blind adalimumab; Drug: Double-blind Placebo; Biological: Open-label Adalimumab; Biological: Open-labelAdalimumabRescue
• Enrollment: 334

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	DB Adalimumab	DB Placebo	DB Adalimumab/OL Adalimumab	DB Placebo/OL Adalimumab	DB Adalimumab/RE OL Adalimumab	DB Placebo/RE OL Adalimumab
Arm/Group Description	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind adalimumab administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
Period Title: Double-blind
Started	171	163	0	0	0	0
Completed	155 [1]	151 [2]	0	0	0	0
Not Completed	16	12	0	0	0	0
[1] 10 participants who completed 26 weeks received open-label adalimumab 40 mg eow as rescue therapy; [2] 24 participants who completed 26 weeks received open-label adalimumab 40 mg eow as rescue therapy
Period Title: Open-label
Started	0	0	145	127	10	24
Completed	0	0	132	120	5	21
Not Completed	0	0	13	7	5	3

Baseline Characteristics

Arm/Group Title		DB Adalimumab	DB Placebo	Total
Arm/Group Description		Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Total of all reporting groups
Overall Number of Baseline Participants		171	163	334
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	171 participants	163 participants	334 participants
		54.0 (13.13)	54.0 (13.20)	54.0 (13.15)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	171 participants	163 participants	334 participants
	Female	144 84.2%	128 78.5%	272 81.4%
	Male	27 15.8%	35 21.5%	62 18.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Japan	Number Analyzed	171 participants	163 participants	334 participants
		171	163	334

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Modified Total Sharp X-Ray Score at Week 26
Description	Modified Total Sharp Score (mTSS) is a measure of joint health, used in evaluation of inhibition of radiographic progression of disease. Digitized X-rays of hands and feet were obtained then scored in a blinded manner: for erosions (0 [no damage] to 5 [complete collapse or total destruction of joint]) and for joint space narrowing (0 [no damage] to 4 [complete luxation of joint]). Scores were added, giving total mTSS (0 [normal] to 380 [maximal disease]). Large positive change in mTSS indicates disease progression; small positive/no change indicates slowing/halting of disease progression.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of double-blind study drug and had at least 1 efficacy assessment during double-blind study drug treatment. Analysis performed using observed cases; no imputation technique used. Participants who switched to open-label adalimumab before Week 26 were excluded from the analysis.

Arm/Group Title	DB Adalimumab	DB Placebo
Arm/Group Description:	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	148	128
Mean (Standard Deviation); Unit of Measure: units on a scale
	1.5 (6.07)	2.4 (3.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DB Adalimumab, DB Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

2. Secondary Outcome

Title	Number of Participants Meeting ACR20 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Description	Patients were ACR20 responders if they had: >= 20% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=20% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of double-blind study drug and had at least 1 efficacy assessment during double-blind study drug treatment. Non-responder imputation (NRI) performed.

Arm/Group Title	DB Adalimumab	DB Placebo
Arm/Group Description:	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	171	163
Measure Type: Number; Unit of Measure: participants
	129	92

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DB Adalimumab, DB Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

3. Secondary Outcome

Title	Number of Participants Meeting ACR50 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Description	Patients were ACR50 responders if they had: >= 50% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=50% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of double-blind study drug and had at least 1 efficacy assessment during double-blind study drug treatment. Non-responder imputation (NRI) performed.

Arm/Group Title	DB Adalimumab	DB Placebo
Arm/Group Description:	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	171	163
Measure Type: Number; Unit of Measure: participants
	110	63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DB Adalimumab, DB Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

4. Secondary Outcome

Title	Number of Participants Meeting ACR70 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Description	Patients were ACR70 responders if they had: >= 70% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=70% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of double-blind study drug and had at least 1 efficacy assessment during double-blind study drug treatment. Non-responder imputation (NRI) performed.

Arm/Group Title	DB Adalimumab	DB Placebo
Arm/Group Description:	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	171	163
Measure Type: Number; Unit of Measure: participants
	81	37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DB Adalimumab, DB Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

5. Secondary Outcome

Title	Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 26
Description	Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of double-blind study drug and had at least 1 efficacy assessment during double-blind study drug treatment. Last observation carried forward (LOCF) was used for missing data.

Arm/Group Title	DB Adalimumab	DB Placebo
Arm/Group Description:	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	171	163
Mean (Standard Deviation); Unit of Measure: units on a scale
	-2.8 (1.63)	-1.8 (1.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DB Adalimumab, DB Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

6. Secondary Outcome

Title	Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 26
Description	Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity. DAS28(ESR) score <2.6 was defined as clinical remission of disease.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of double-blind study drug and had at least 1 efficacy assessment during double-blind study drug treatment. Non-responder imputation (NRI) performed.

Arm/Group Title	DB Adalimumab	DB Placebo
Arm/Group Description:	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	171	163
Measure Type: Number; Unit of Measure: participants
	52	24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DB Adalimumab, DB Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

7. Secondary Outcome

Title	Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) on Double-blind Study Drug Through Week 26
Description	Adverse events were collected at designated study visits for all participants who were randomized and received at least 1 dose of study drug. The number of participants who experienced any adverse event (serious or non-serious) while receiving double-blind study drug is summarized. See the Reported Adverse Event section for details.
Time Frame	Through Week 26

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of double-blind study drug.

Arm/Group Title	DB Adalimumab	DB Placebo
Arm/Group Description:	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	171	163
Measure Type: Number; Unit of Measure: participants
	138	117

8. Secondary Outcome

Title	Change From Baseline in Modified Total Sharp X-Ray Score at Week 52
Description	Modified Total Sharp Score (mTSS) is a measure of joint health, used in evaluation of inhibition of radiographic progression of disease. Digitized X-rays of hands and feet were obtained then scored in a blinded manner: for erosions (0 [no damage] to 5 [complete collapse or total destruction of joint]) and for joint space narrowing (0 [no damage] to 4 [complete luxation of joint]). Scores were added, giving total mTSS score (0 [normal] to 380 [maximal disease]). Large positive change in mTSS indicates diseae progression; small positive/no change indicates slowing/halting of disease progression.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Participants who completed 26 weeks and received at least 1 dose of adalimumab after Week 26. Analysis performed using observed cases; no imputation technique used.

Arm/Group Title	DB Adalimumab/OL Adalimumab	DB Placebo/OL Adalimumab	DB Adalimumab/RE OL Adalimumab	DB Placebo/RE OL Adalimumab
Arm/Group Description:	Participants received double-blind adalimumab administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	133	120	5	21
Mean (Standard Deviation); Unit of Measure: units on a scale
	1.6 (6.50)	2.1 (3.25)	9.6 (11.76)	6.8 (9.37)

9. Secondary Outcome

Title	Number of Participants Meeting ACR20 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Description	Patients were ACR20 responders if they had: >=20% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=20% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Participants who completed the first 26 weeks and received at least 1 dose of adalimumab after Week 26. Analysis performed using observed cases; no imputation technique used.

Arm/Group Title	DB Adalimumab/OL Adalimumab	DB Placebo/OL Adalimumab	DB Adalimumab/RE OL Adalimumab	DB Placebo/RE OL Adalimumab
Arm/Group Description:	Participants received double-blind adalimumab administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	133	120	5	21
Measure Type: Number; Unit of Measure: participants
	129	113	4	21

10. Secondary Outcome

Title	Number of Participants Meeting ACR50 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Description	Patients were ACR50 responders if they had: >=50% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=50% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Participants who completed the first 26 weeks and received at least 1 dose of adalimumab after Week 26. Analysis performed using observed cases; no imputation technique used.

Arm/Group Title	DB Adalimumab/OL Adalimumab	DB Placebo/OL Adalimumab	DB Adalimumab/RE OL Adalimumab	DB Placebo/RE OL Adalimumab
Arm/Group Description:	Participants received double-blind adalimumab administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	133	120	5	21
Measure Type: Number; Unit of Measure: participants
	117	101	2	15

11. Secondary Outcome

Title	Number of Participants Meeting ACR70 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Description	Patients were ACR70 responders if they had: >=70% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=70% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Participants who completed the first 26 weeks and received at least 1 dose of adalimumab after Week 26. Analysis performed using observed cases; no imputation technique used.

Arm/Group Title	DB Adalimumab/OL Adalimumab	DB Placebo/OL Adalimumab	DB Adalimumab/RE OL Adalimumab	DB Placebo/RE OL Adalimumab
Arm/Group Description:	Participants received double-blind adalimumab administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	133	120	5	21
Measure Type: Number; Unit of Measure: participants
	87	85	0	10

12. Secondary Outcome

Title	Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 52
Description	Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Participants who completed the first 26 weeks and received at least 1 dose of adalimumab after Week 26. Analysis performed using observed cases; no imputation technique used.

Arm/Group Title	DB Adalimumab/OL Adalimumab	DB Placebo/OL Adalimumab	DB Adalimumab/RE OL Adalimumab	DB Placebo/RE OL Adalimumab
Arm/Group Description:	Participants received double-blind adalimumab administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	133	120	5	21
Mean (Standard Deviation); Unit of Measure: units on a scale
	-3.7 (1.14)	-3.7 (1.58)	-1.9 (1.22)	-3.4 (1.29)

13. Secondary Outcome

Title	Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 52
Description	Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity. DAS28(ESR) score <2.6 was defined as clinical remission of disease.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Participants who completed the first 26 weeks and received at least 1 dose of adalimumab after Week 26. Analysis performed using observed cases; no imputation technique used.

Arm/Group Title	DB Adalimumab/OL Adalimumab	DB Placebo/OL Adalimumab	DB Adalimumab/RE OL Adalimumab	DB Placebo/RE OL Adalimumab
Arm/Group Description:	Participants received double-blind adalimumab administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible) to complete 26 weeks, followed by open-label 40 mg SC eow for up to 26 weeks. Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
Overall Number of Participants Analyzed	133	120	5	21
Measure Type: Number; Unit of Measure: participants
	62	55	0	4

14. Secondary Outcome

Title	Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) While Receiving Adalimumab Through Week 52
Description	Adverse events were collected at designated study visits for all participants who were randomized and received at least 1 dose of adalimumab. The number of participants who experienced any adverse event (serious or non-serious) while receiving any adalimumab during the study (double-blind adalimumab and/or open-label) is summarized. See the Reported Adverse Event section for details.
Time Frame	Through Week 52

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of adalimumab during the study.

Arm/Group Title	Any Adalimumab
Arm/Group Description:	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and/or open-label adalimumab 40 mg SC eow, including as rescue treatment.
Overall Number of Participants Analyzed	326
Measure Type: Number; Unit of Measure: participants
	289

Adverse Events

Time Frame	Through Week 26 for all participants who received at least 1 dose of blinded study drug (adalimumab or placebo) or through Week 52 for participants who received any adalimumab (double-blind and/or open-label, including rescue) in addition to methotrexate.
Adverse Event Reporting Description	Treatment-emergent adverse events were defined as occurring: 1) through Week 26 for Week 26 completers in blinded phase (or up to 70 days post-last dose for 26-week non-completers who never received any open-label adalimumab, including as rescue) and 2) through Week 52 for those receiving any adalimumab up to 70 days after the last adalimumab dose.
Arm/Group Title	DB Adalimumab	DB Placebo	Any Adalimumab
Arm/Group Description	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks. Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.	Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and/or open-label adalimumab 40 mg SC eow, including as rescue treatment.
All-Cause Mortality
	DB Adalimumab	DB Placebo	Any Adalimumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	DB Adalimumab	DB Placebo	Any Adalimumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	7/171 (4.09%)	4/163 (2.45%)	21/326 (6.44%)
Cardiac disorders
Acute myocardial infarction * 1	0/171 (0.00%)	1/163 (0.61%)	0/326 (0.00%)
Ear and labyrinth disorders
Vertigo positional * 1	1/171 (0.58%)	0/163 (0.00%)	1/326 (0.31%)
Eye disorders
Cataract * 1	0/171 (0.00%)	0/163 (0.00%)	2/326 (0.61%)
Gastrointestinal disorders
Colonic polyp * 1	0/171 (0.00%)	0/163 (0.00%)	1/326 (0.31%)
Pancreatitis acute * 1	0/171 (0.00%)	0/163 (0.00%)	1/326 (0.31%)
Hepatobiliary disorders
Cholangitis acute * 1	0/171 (0.00%)	0/163 (0.00%)	1/326 (0.31%)
Cholecystitis * 1	0/171 (0.00%)	0/163 (0.00%)	1/326 (0.31%)
Infections and infestations
Enteritis infectious * 1	1/171 (0.58%)	0/163 (0.00%)	1/326 (0.31%)
Pneumocystis jiroveci pneumonia * 1	0/171 (0.00%)	1/163 (0.61%)	0/326 (0.00%)
Pneumonia * 1	1/171 (0.58%)	0/163 (0.00%)	4/326 (1.23%)
Bronchopneumonia * 1	0/171 (0.00%)	0/163 (0.00%)	1/326 (0.31%)
Gastroenteritis * 1	0/171 (0.00%)	0/163 (0.00%)	2/326 (0.61%)
Injury, poisoning and procedural complications
Pelvic fracture * 1	1/171 (0.58%)	0/163 (0.00%)	1/326 (0.31%)
Ulna fracture * 1	1/171 (0.58%)	0/163 (0.00%)	1/326 (0.31%)
Investigations
C-reactive protein increased † 1	0/171 (0.00%)	0/163 (0.00%)	1/326 (0.31%)
Musculoskeletal and connective tissue disorders
Back pain * 1	0/171 (0.00%)	1/163 (0.61%)	0/326 (0.00%)
Rheumatoid arthritis * 1	0/171 (0.00%)	1/163 (0.61%)	0/326 (0.00%)
Systemic lupus erythematosus * 1	0/171 (0.00%)	1/163 (0.61%)	0/326 (0.00%)
Arthritis * 1	0/171 (0.00%)	0/163 (0.00%)	1/326 (0.31%)
Intervertebral disc protrusion * 1	0/171 (0.00%)	0/163 (0.00%)	1/326 (0.31%)
Pain in extremity * 1	0/171 (0.00%)	0/163 (0.00%)	1/326 (0.31%)
Nervous system disorders
Facial spasm * 1	1/171 (0.58%)	0/163 (0.00%)	1/326 (0.31%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease * 1	0/171 (0.00%)	1/163 (0.61%)	1/326 (0.31%)
Pleurisy * 1	1/171 (0.58%)	0/163 (0.00%)	1/326 (0.31%)
Organising pneumonia * 1	0/171 (0.00%)	0/163 (0.00%)	1/326 (0.31%)
Skin and subcutaneous tissue disorders
Toxic skin eruption * 1	1/171 (0.58%)	0/163 (0.00%)	1/326 (0.31%)
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 13.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	DB Adalimumab	DB Placebo	Any Adalimumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	104/171 (60.82%)	83/163 (50.92%)	277/326 (84.97%)
Gastrointestinal disorders
Constipation * 1	4/171 (2.34%)	2/163 (1.23%)	14/326 (4.29%)
Diarrhoea * 1	5/171 (2.92%)	1/163 (0.61%)	18/326 (5.52%)
Periodontitis * 1	5/171 (2.92%)	5/163 (3.07%)	9/326 (2.76%)
Stomatitis * 1	6/171 (3.51%)	15/163 (9.20%)	17/326 (5.21%)
Dental caries * 1	3/171 (1.75%)	2/163 (1.23%)	9/326 (2.76%)
Gastritis * 1	2/171 (1.17%)	1/163 (0.61%)	10/326 (3.07%)
Nausea * 1	2/171 (1.17%)	3/163 (1.84%)	7/326 (2.15%)
General disorders
Injection site erythema * 1	5/171 (2.92%)	3/163 (1.84%)	8/326 (2.45%)
Injection site reaction * 1	10/171 (5.85%)	1/163 (0.61%)	28/326 (8.59%)
Pyrexia * 1	5/171 (2.92%)	3/163 (1.84%)	8/326 (2.45%)
Hepatobiliary disorders
Hepatic function abnormal * 1	14/171 (8.19%)	9/163 (5.52%)	24/326 (7.36%)
Liver disorder * 1	4/171 (2.34%)	3/163 (1.84%)	9/326 (2.76%)
Hepatic steatosis * 1	1/171 (0.58%)	0/163 (0.00%)	7/326 (2.15%)
Infections and infestations
Bronchitis * 1	4/171 (2.34%)	4/163 (2.45%)	13/326 (3.99%)
Gastroenteritis * 1	2/171 (1.17%)	4/163 (2.45%)	8/326 (2.45%)
Nasopharyngitis * 1	26/171 (15.20%)	27/163 (16.56%)	97/326 (29.75%)
Pharyngitis * 1	2/171 (1.17%)	4/163 (2.45%)	16/326 (4.91%)
Cystitis * 1	3/171 (1.75%)	1/163 (0.61%)	11/326 (3.37%)
Herpes zoster * 1	1/171 (0.58%)	1/163 (0.61%)	7/326 (2.15%)
Upper respiratory tract infection * 1	2/171 (1.17%)	0/163 (0.00%)	7/326 (2.15%)
Injury, poisoning and procedural complications
Contusion * 1	3/171 (1.75%)	4/163 (2.45%)	14/326 (4.29%)
Fall * 1	5/171 (2.92%)	0/163 (0.00%)	15/326 (4.60%)
Investigations
Alanine aminotransferase increased † 1	13/171 (7.60%)	6/163 (3.68%)	28/326 (8.59%)
Aspartate aminotransferase increased † 1	11/171 (6.43%)	5/163 (3.07%)	22/326 (6.75%)
Blood cholesterol increased † 1	4/171 (2.34%)	0/163 (0.00%)	5/326 (1.53%)
Liver function test abnormal † 1	3/171 (1.75%)	2/163 (1.23%)	8/326 (2.45%)
White blood cell count decreased † 1	3/171 (1.75%)	1/163 (0.61%)	9/326 (2.76%)
Metabolism and nutrition disorders
Hyperlipidaemia † 1	3/171 (1.75%)	0/163 (0.00%)	7/326 (2.15%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis * 1	0/171 (0.00%)	4/163 (2.45%)	2/326 (0.61%)
Back pain * 1	3/171 (1.75%)	3/163 (1.84%)	14/326 (4.29%)
Nervous system disorders
Dizziness * 1	1/171 (0.58%)	3/163 (1.84%)	7/326 (2.15%)
Headache * 1	3/171 (1.75%)	3/163 (1.84%)	12/326 (3.68%)
Psychiatric disorders
Insomnia * 1	1/171 (0.58%)	4/163 (2.45%)	5/326 (1.53%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	4/171 (2.34%)	3/163 (1.84%)	7/326 (2.15%)
Oropharyngeal pain * 1	4/171 (2.34%)	1/163 (0.61%)	9/326 (2.76%)
Upper respiratory tract inflammation * 1	6/171 (3.51%)	4/163 (2.45%)	28/326 (8.59%)
Skin and subcutaneous tissue disorders
Dermatitis contact * 1	1/171 (0.58%)	4/163 (2.45%)	7/326 (2.15%)
Eczema * 1	6/171 (3.51%)	6/163 (3.68%)	24/326 (7.36%)
Eczema asteatotic * 1	4/171 (2.34%)	0/163 (0.00%)	4/326 (1.23%)
Pruritus * 1	4/171 (2.34%)	1/163 (0.61%)	5/326 (1.53%)
Rash * 1	10/171 (5.85%)	5/163 (3.07%)	26/326 (7.98%)
Urticaria * 1	0/171 (0.00%)	2/163 (1.23%)	8/326 (2.45%)
Vascular disorders
Hypertension * 1	5/171 (2.92%)	8/163 (4.91%)	12/326 (3.68%)
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 13.1

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.

Abbott requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. Abbott requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Abbott needs to secure patent or proprietary protection.

Results Point of Contact

• Name/Title: Global Medical Services
• Organization: Abbott
• Phone: 800-633-9110

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

Burmester GR, Landewe R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Feb;76(2):414-417. doi: 10.1136/annrheumdis-2016-209322. Epub 2016 Jun 23.

Yamanaka H, Ishiguro N, Takeuchi T, Miyasaka N, Mukai M, Matsubara T, Uchida S, Akama H, Kupper H, Arora V, Tanaka Y. Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial. Rheumatology (Oxford). 2014 May;53(5):904-13. doi: 10.1093/rheumatology/ket465. Epub 2014 Jan 17.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT00870467
• Other Study ID Numbers: M06-859
• First Submitted: March 26, 2009
• First Posted: March 27, 2009
• Results First Submitted: March 9, 2012
• Results First Posted: April 5, 2012
• Last Update Posted: August 7, 2012