A Study of Adalimumab in Japanese Subjects With Rheumatoid Arthritis

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00870467
• Collaborator: Eisai Co., Ltd. (Industry)
• Enrollment: 334
• Locations: 88
• Arms: 6
• Duration (Months): 29
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the potential of adalimumab to inhibit radiographic progression in joint destruction compared with placebo in adult Japanese subjects with recent onset of rheumatoid arthritis.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Biological: Double-blind adalimumab; Drug: Double-blind Placebo; Biological: Open-label Adalimumab; Biological: Open-labelAdalimumabRescue	Phase 3

Detailed Description

This was a Phase 3 multicenter, randomized, double-blind, parallel group, placebo-controlled study designed to evaluate the inhibition of radiographic progression by adalimumab compared with placebo in adult Japanese patients with early rheumatoid arthritis (RA) who had not been previously treated with methotrexate (MTX). Eligible participants were randomized 1:1 to receive either a subcutaneous injection of adalimumab 40 mg or matching placebo every other week (eow) during the 26-week double-blind phase. All participants also received 6 mg to 8 mg MTX weekly as basal treatment for their disease. Participants who experienced an increase in disease activity (more than 20% increase in tender joint count and swollen joint count) at Week 12, 16, or 20 compared with Baseline after having increased MTX dose to 8 mg per week for at least 4 weeks were discontinued from the double-blind phase and were eligible to receive open-label adalimumab 40 mg eow as rescue treatment. Participants who completed the 26 weeks of treatment (either double-blind study drug [adalimumab or placebo] treatment or open-label adalimumab treatment) were eligible to enter the 26-week open-label phase in which they received adalimumab 40 mg eow. Efficacy and safety assessments were performed at Baseline and at designated study visits.

Study Design

• Study Type: Interventional
• Actual Enrollment: 334 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Multi-Center, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study Comparing Adalimumab and Placebo in Adult Japanese Subjects With Rheumatoid Arthritis
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: DB Placebo 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.	Drug: Double-blind Placebo; Double-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow); Other Names: Placebo
Experimental: DB adalimumab 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.	Biological: Double-blind adalimumab; Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow); Other Names: ABT-D2E7, adalimumab, Humira
Experimental: DB Adalimumab/OL Adalimumab 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.	Biological: Double-blind adalimumab; Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow); Other Names: ABT-D2E7, adalimumab, Humira ; Biological: Open-label Adalimumab; Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study; Other Names: ABT-D2E7 adalimumab Humira
Experimental: DB Placebo/OL Adalimumab 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.	Drug: Double-blind Placebo; Double-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow); Other Names: Placebo ; Biological: Open-label Adalimumab; Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study; Other Names: ABT-D2E7 adalimumab Humira
Experimental: DB Adalimumab/RE OL Adalimumab 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 at Week 12 or after) 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.	Biological: Double-blind adalimumab; Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow); Other Names: ABT-D2E7, adalimumab, Humira ; Biological: Open-label Adalimumab; Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study; Other Names: ABT-D2E7 adalimumab Humira ; Biological: Open-labelAdalimumabRescue; Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) as rescue treatment to complete the first 26 weeks in the study- dependent on participant eligibility (increase in disease activity), applies to Weeks 12 to 26; Other Names: ABT-D2E7 adalimumab Humira
Experimental: DB Placebo/RE OL Adalimumab 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 at Week 12 or after) 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.	Drug: Double-blind Placebo; Double-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow); Other Names: Placebo ; Biological: Open-label Adalimumab; Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study; Other Names: ABT-D2E7 adalimumab Humira ; Biological: Open-labelAdalimumabRescue; Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) as rescue treatment to complete the first 26 weeks in the study- dependent on participant eligibility (increase in disease activity), applies to Weeks 12 to 26; Other Names: ABT-D2E7 adalimumab Humira

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Modified Total Sharp X-Ray Score at Week 26 [Baseline, Week 26]

   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.

Secondary Outcome Measures

1. Number of Participants Meeting ACR20 Response Criteria at Week 26 (ACR: American College of Rheumatology) [Week 26]

   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.

2. Number of Participants Meeting ACR50 Response Criteria at Week 26 (ACR: American College of Rheumatology) [Week 26]

   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.

3. Number of Participants Meeting ACR70 Response Criteria at Week 26 (ACR: American College of Rheumatology) [Week 26]

   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.

4. Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 26 [Baseline, Week 26]

   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.

5. Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 26 [Week 26]

   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.

6. Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) on Double-blind Study Drug Through Week 26 [Through Week 26]

   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.

7. Change From Baseline in Modified Total Sharp X-Ray Score at Week 52 [Baseline, Week 52]

   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.

8. Number of Participants Meeting ACR20 Response Criteria at Week 52 (ACR: American College of Rheumatology) [Week 52]

   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.

9. Number of Participants Meeting ACR50 Response Criteria at Week 52 (ACR: American College of Rheumatology) [Week 52]

   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.

10. Number of Participants Meeting ACR70 Response Criteria at Week 52 (ACR: American College of Rheumatology) [Week 52]

    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.

11. Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 52 [Baseline, Week 52]

    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.

12. Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 52 [Week 52]

    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.

13. Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) While Receiving Adalimumab Through Week 52 [Through Week 52]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Rheumatoid arthritis based on the American College of Rheumatology criteria

• Methotrexate or leflunomide naïve

• Disease duration less than or equal to 2 years from diagnosis

Exclusion Criteria

• History of acute inflammatory joint disease of different origin from rheumatoid arthritis, cancer, lymphoma, leukemia or lymphoproliferative disease, active TB, HIV

• Previously received anti-TNF therapy anti-IL-6 receptor antibody, CTLA4-Ig, anti-CD20 antibody, cyclophosphamide, cyclosporine, azathioprine, or tacrolimus

• Joint surgery involving joints to be assessed within 8 weeks prior to Screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Reference ID/Investigator# 46861	Anjo		Japan
2	Site Reference ID/Investigator# 46919	Aomori		Japan
3	Site Reference ID/Investigator# 46805	Chiba		Japan
4	Site Reference ID/Investigator# 46806	Chiba		Japan
5	Site Reference ID/Investigator# 46880	Chiba		Japan
6	Site Reference ID/Investigator# 46881	Chiba		Japan
7	Site Reference ID/Investigator# 46890	Fuchu		Japan
8	Site Reference ID/Investigator# 46902	Fukuoka		Japan
9	Site Reference ID/Investigator# 46903	Fukuoka		Japan
10	Site Reference ID/Investigator# 46904	Fukuoka		Japan
11	Site Reference ID/Investigator# 46856	Gifu		Japan
12	Site Reference ID/Investigator# 46944	Gunma		Japan
13	Site Reference ID/Investigator# 46893	Hiroshima		Japan
14	Site Reference ID/Investigator# 46894	Hiroshima		Japan
15	Site Reference ID/Investigator# 12161	Hokkaido		Japan
16	Site Reference ID/Investigator# 46916	Hokkaido		Japan
17	Site Reference ID/Investigator# 46918	Hokkaido		Japan
18	Site Reference ID/Investigator# 46865	Hyogo		Japan
19	Site Reference ID/Investigator# 46871	Hyogo		Japan
20	Site Reference ID/Investigator# 46801	Ibaraki		Japan
21	Site Reference ID/Investigator# 46925	Ibaraki		Japan
22	Site Reference ID/Investigator# 46800	Iwate		Japan
23	Site Reference ID/Investigator# 46873	Kagoshima		Japan
24	Site Reference ID/Investigator# 46874	Kagoshima		Japan
25	Site Reference ID/Investigator# 46845	Kanagawa		Japan
26	Site Reference ID/Investigator# 46899	Kanagawa		Japan
27	Site Reference ID/Investigator# 46901	Kanagawa		Japan
28	Site Reference ID/Investigator# 46851	Kanazawa		Japan
29	Site Reference ID/Investigator# 46852	Kanazawa		Japan
30	Site Reference ID/Investigator# 46802	Kawagoe		Japan
31	Site Reference ID/Investigator# 46900	Kawasaki		Japan
32	Site Reference ID/Investigator# 46875	Kirishima		Japan
33	Site Reference ID/Investigator# 46870	Kitakyushu		Japan
34	Site Reference ID/Investigator# 46872	Kumamoto		Japan
35	Site Reference ID/Investigator# 46912	Kumamoto		Japan
36	Site Reference ID/Investigator# 46864	Kyoto		Japan
37	Site Reference ID/Investigator# 46943	Maebashi		Japan
38	Site Reference ID/Investigator# 46898	Matsuyama		Japan
39	Site Reference ID/Investigator# 46915	Miyazaki		Japan
40	Site Reference ID/Investigator# 46853	Nagano		Japan
41	Site Reference ID/Investigator# 46855	Nagano		Japan
42	Site Reference ID/Investigator# 46909	Nagasaki		Japan
43	Site Reference ID/Investigator# 46910	Nagasaki		Japan
44	Site Reference ID/Investigator# 46911	Nagasaki		Japan
45	Site Reference ID/Investigator# 46858	Nagoya		Japan
46	Site Reference ID/Investigator# 46860	Nagoya		Japan
47	Site Reference ID/Investigator# 46877	Nara		Japan
48	Site Reference ID/Investigator# 46885	Nara		Japan
49	Site Reference ID/Investigator# 46848	Niigata		Japan
50	Site Reference ID/Investigator# 46906	Niigata		Japan
51	Site Reference ID/Investigator# 46914	Oita		Japan
52	Site Reference ID/Investigator# 46869	Okayama		Japan
53	Site Reference ID/Investigator# 46886	Okayama		Japan
54	Site Reference ID/Investigator# 46887	Okayama		Japan
55	Site Reference ID/Investigator# 46892	Okayama		Japan
56	Site Reference ID/Investigator# 46876	Okinawa		Japan
57	Site Reference ID/Investigator# 46946	Osaka		Japan
58	Site Reference ID/Investigator# 46947	Osaka		Japan
59	Site Reference ID/Investigator# 46842	Rifu		Japan
60	Site Reference ID/Investigator# 46846	Sagamihara		Japan
61	Site Reference ID/Investigator# 46803	Saitama		Japan
62	Site Reference ID/Investigator# 46804	Saitama		Japan
63	Site Reference ID/Investigator# 46878	Saitama		Japan
64	Site Reference ID/Investigator# 46879	Saitama		Japan
65	Site Reference ID/Investigator# 46917	Sapporo		Japan
66	Site Reference ID/Investigator# 46942	Shimotsuke		Japan
67	Site Reference ID/Investigator# 46854	Shizuoka		Japan
68	Site Reference ID/Investigator# 46857	Shizuoka		Japan
69	Site Reference ID/Investigator# 46859	Shizuoka		Japan
70	Site Reference ID/Investigator# 46895	Takamatsu		Japan
71	Site Reference ID/Investigator# 46843	Tokyo		Japan
72	Site Reference ID/Investigator# 46844	Tokyo		Japan
73	Site Reference ID/Investigator# 46850	Tokyo		Japan
74	Site Reference ID/Investigator# 46882	Tokyo		Japan
75	Site Reference ID/Investigator# 46883	Tokyo		Japan
76	Site Reference ID/Investigator# 46884	Tokyo		Japan
77	Site Reference ID/Investigator# 46888	Tokyo		Japan
78	Site Reference ID/Investigator# 46889	Tokyo		Japan
79	Site Reference ID/Investigator# 46891	Tokyo		Japan
80	Site Reference ID/Investigator# 46896	Tokyo		Japan
81	Site Reference ID/Investigator# 46849	Toyama		Japan
82	Site Reference ID/Investigator# 46907	Toyama		Japan
83	Site Reference ID/Investigator# 46862	Toyoake		Japan
84	Site Reference ID/Investigator# 46866	Toyohashi		Japan
85	Site Reference ID/Investigator# 46926	Tsukuba		Japan
86	Site Reference ID/Investigator# 46863	Tsu		Japan
87	Site Reference ID/Investigator# 46897	Yokohama		Japan
88	Site Reference ID/Investigator# 46905	Yokohama		Japan

Sponsors and Collaborators

• Abbott
• Eisai Co., Ltd.

Investigators

• Study Director: Hiroshi Ukai, BS, Abbott Japan Co.,Ltd

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT00870467
• Other Study ID Numbers: M06-859
• First Posted: Mar 27, 2009
• Last Update Posted: Aug 7, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by Abbott: Rheumatoid Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Adalimumab

Study Results

Participant Flow

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	151	0	0	0	0
NOT COMPLETED	16	12	0	0	0	0
Period Title: Double-blind
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 Participants	171	163	334
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.0 (13.13)	54.0 (13.20)	54.0 (13.15)
Sex: Female, Male (Count of Participants)
Female	144 84.2%	128 78.5%	272 81.4%
Male	27 15.8%	35 21.5%	62 18.6%
Region of Enrollment (participants) [Number]
Japan	171 100%	163 100%	334 100%

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.
Measure Participants	148	128
Mean (Standard Deviation) [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
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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.
Measure Participants	171	163
Number [participants]	129 75.4%	92 56.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DB Adalimumab, DB Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

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.
Measure Participants	171	163
Number [participants]	110 64.3%	63 38.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DB Adalimumab, DB Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

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.
Measure Participants	171	163
Number [participants]	81 47.4%	37 22.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DB Adalimumab, DB Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

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.
Measure Participants	171	163
Mean (Standard Deviation) [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
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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.
Measure Participants	171	163
Number [participants]	52 30.4%	24 14.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DB Adalimumab, DB Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

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.
Measure Participants	171	163
Number [participants]	138 80.7%	117 71.8%

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.
Measure Participants	133	120	5	21
Mean (Standard Deviation) [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.
Measure Participants	133	120	5	21
Number [participants]	129 75.4%	113 69.3%	4 1.2%	21 NaN

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.
Measure Participants	133	120	5	21
Number [participants]	117 68.4%	101 62%	2 0.6%	15 NaN

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.
Measure Participants	133	120	5	21
Number [participants]	87 50.9%	85 52.1%	0 0%	10 NaN

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.
Measure Participants	133	120	5	21
Mean (Standard Deviation) [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.
Measure Participants	133	120	5	21
Number [participants]	62 36.3%	55 33.7%	0 0%	4 NaN

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.
Measure Participants	326
Number [participants]	289 169%

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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	DB Adalimumab		DB Placebo		Any Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/171 (4.1%)		4/163 (2.5%)		21/326 (6.4%)
Cardiac disorders
Acute myocardial infarction	0/171 (0%)		1/163 (0.6%)		0/326 (0%)
Ear and labyrinth disorders
Vertigo positional	1/171 (0.6%)		0/163 (0%)		1/326 (0.3%)
Eye disorders
Cataract	0/171 (0%)		0/163 (0%)		2/326 (0.6%)
Gastrointestinal disorders
Colonic polyp	0/171 (0%)		0/163 (0%)		1/326 (0.3%)
Pancreatitis acute	0/171 (0%)		0/163 (0%)		1/326 (0.3%)
Hepatobiliary disorders
Cholangitis acute	0/171 (0%)		0/163 (0%)		1/326 (0.3%)
Cholecystitis	0/171 (0%)		0/163 (0%)		1/326 (0.3%)
Infections and infestations
Enteritis infectious	1/171 (0.6%)		0/163 (0%)		1/326 (0.3%)
Pneumocystis jiroveci pneumonia	0/171 (0%)		1/163 (0.6%)		0/326 (0%)
Pneumonia	1/171 (0.6%)		0/163 (0%)		4/326 (1.2%)
Bronchopneumonia	0/171 (0%)		0/163 (0%)		1/326 (0.3%)
Gastroenteritis	0/171 (0%)		0/163 (0%)		2/326 (0.6%)
Injury, poisoning and procedural complications
Pelvic fracture	1/171 (0.6%)		0/163 (0%)		1/326 (0.3%)
Ulna fracture	1/171 (0.6%)		0/163 (0%)		1/326 (0.3%)
Investigations
C-reactive protein increased	0/171 (0%)		0/163 (0%)		1/326 (0.3%)
Musculoskeletal and connective tissue disorders
Back pain	0/171 (0%)		1/163 (0.6%)		0/326 (0%)
Rheumatoid arthritis	0/171 (0%)		1/163 (0.6%)		0/326 (0%)
Systemic lupus erythematosus	0/171 (0%)		1/163 (0.6%)		0/326 (0%)
Arthritis	0/171 (0%)		0/163 (0%)		1/326 (0.3%)
Intervertebral disc protrusion	0/171 (0%)		0/163 (0%)		1/326 (0.3%)
Pain in extremity	0/171 (0%)		0/163 (0%)		1/326 (0.3%)
Nervous system disorders
Facial spasm	1/171 (0.6%)		0/163 (0%)		1/326 (0.3%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	0/171 (0%)		1/163 (0.6%)		1/326 (0.3%)
Pleurisy	1/171 (0.6%)		0/163 (0%)		1/326 (0.3%)
Organising pneumonia	0/171 (0%)		0/163 (0%)		1/326 (0.3%)
Skin and subcutaneous tissue disorders
Toxic skin eruption	1/171 (0.6%)		0/163 (0%)		1/326 (0.3%)
Other (Not Including Serious) Adverse Events
	DB Adalimumab		DB Placebo		Any Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	104/171 (60.8%)		83/163 (50.9%)		277/326 (85%)
Gastrointestinal disorders
Constipation	4/171 (2.3%)		2/163 (1.2%)		14/326 (4.3%)
Diarrhoea	5/171 (2.9%)		1/163 (0.6%)		18/326 (5.5%)
Periodontitis	5/171 (2.9%)		5/163 (3.1%)		9/326 (2.8%)
Stomatitis	6/171 (3.5%)		15/163 (9.2%)		17/326 (5.2%)
Dental caries	3/171 (1.8%)		2/163 (1.2%)		9/326 (2.8%)
Gastritis	2/171 (1.2%)		1/163 (0.6%)		10/326 (3.1%)
Nausea	2/171 (1.2%)		3/163 (1.8%)		7/326 (2.1%)
General disorders
Injection site erythema	5/171 (2.9%)		3/163 (1.8%)		8/326 (2.5%)
Injection site reaction	10/171 (5.8%)		1/163 (0.6%)		28/326 (8.6%)
Pyrexia	5/171 (2.9%)		3/163 (1.8%)		8/326 (2.5%)
Hepatobiliary disorders
Hepatic function abnormal	14/171 (8.2%)		9/163 (5.5%)		24/326 (7.4%)
Liver disorder	4/171 (2.3%)		3/163 (1.8%)		9/326 (2.8%)
Hepatic steatosis	1/171 (0.6%)		0/163 (0%)		7/326 (2.1%)
Infections and infestations
Bronchitis	4/171 (2.3%)		4/163 (2.5%)		13/326 (4%)
Gastroenteritis	2/171 (1.2%)		4/163 (2.5%)		8/326 (2.5%)
Nasopharyngitis	26/171 (15.2%)		27/163 (16.6%)		97/326 (29.8%)
Pharyngitis	2/171 (1.2%)		4/163 (2.5%)		16/326 (4.9%)
Cystitis	3/171 (1.8%)		1/163 (0.6%)		11/326 (3.4%)
Herpes zoster	1/171 (0.6%)		1/163 (0.6%)		7/326 (2.1%)
Upper respiratory tract infection	2/171 (1.2%)		0/163 (0%)		7/326 (2.1%)
Injury, poisoning and procedural complications
Contusion	3/171 (1.8%)		4/163 (2.5%)		14/326 (4.3%)
Fall	5/171 (2.9%)		0/163 (0%)		15/326 (4.6%)
Investigations
Alanine aminotransferase increased	13/171 (7.6%)		6/163 (3.7%)		28/326 (8.6%)
Aspartate aminotransferase increased	11/171 (6.4%)		5/163 (3.1%)		22/326 (6.7%)
Blood cholesterol increased	4/171 (2.3%)		0/163 (0%)		5/326 (1.5%)
Liver function test abnormal	3/171 (1.8%)		2/163 (1.2%)		8/326 (2.5%)
White blood cell count decreased	3/171 (1.8%)		1/163 (0.6%)		9/326 (2.8%)
Metabolism and nutrition disorders
Hyperlipidaemia	3/171 (1.8%)		0/163 (0%)		7/326 (2.1%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	0/171 (0%)		4/163 (2.5%)		2/326 (0.6%)
Back pain	3/171 (1.8%)		3/163 (1.8%)		14/326 (4.3%)
Nervous system disorders
Dizziness	1/171 (0.6%)		3/163 (1.8%)		7/326 (2.1%)
Headache	3/171 (1.8%)		3/163 (1.8%)		12/326 (3.7%)
Psychiatric disorders
Insomnia	1/171 (0.6%)		4/163 (2.5%)		5/326 (1.5%)
Respiratory, thoracic and mediastinal disorders
Cough	4/171 (2.3%)		3/163 (1.8%)		7/326 (2.1%)
Oropharyngeal pain	4/171 (2.3%)		1/163 (0.6%)		9/326 (2.8%)
Upper respiratory tract inflammation	6/171 (3.5%)		4/163 (2.5%)		28/326 (8.6%)
Skin and subcutaneous tissue disorders
Dermatitis contact	1/171 (0.6%)		4/163 (2.5%)		7/326 (2.1%)
Eczema	6/171 (3.5%)		6/163 (3.7%)		24/326 (7.4%)
Eczema asteatotic	4/171 (2.3%)		0/163 (0%)		4/326 (1.2%)
Pruritus	4/171 (2.3%)		1/163 (0.6%)		5/326 (1.5%)
Rash	10/171 (5.8%)		5/163 (3.1%)		26/326 (8%)
Urticaria	0/171 (0%)		2/163 (1.2%)		8/326 (2.5%)
Vascular disorders
Hypertension	5/171 (2.9%)		8/163 (4.9%)		12/326 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.