Trial Outcomes & Findings for A Canadian Study to Evaluate Early Use of Adalimumab After Methotrexate Failure in Early Rheumatoid Arthritis (NCT NCT01162421)

Last Updated: 2016-11-01

Results Overview

Radiographic progression was defined as change from Baseline in the modified Total Sharp Score (mTSS) of ≤ 0.5 units). The mTSS is a measure of change in joint health: digitized images of radiographs of hands and feet obtained at Screening and Month 12 were scored in a blinded manner. Joints were scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 \[normal\] to 398 \[maximal disease\]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

77 participants

Primary outcome timeframe

Baseline, Month 12

Results posted on

2016-11-01

Participant Flow

Participant milestones

Participant milestones
Measure	Standard of Care Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Overall Study STARTED	37	40
Overall Study COMPLETED	29	27
Overall Study NOT COMPLETED	8	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard of Care Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Overall Study Did not receive study drug	2	1
Overall Study Adverse Event	2	5
Overall Study Lost to Follow-up	0	2
Overall Study Lack of Efficacy	2	2
Overall Study Other	2	3

Baseline Characteristics

A Canadian Study to Evaluate Early Use of Adalimumab After Methotrexate Failure in Early Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.	Total n=74 Participants Total of all reporting groups
Age, Continuous	53.8 years STANDARD_DEVIATION 10.46 • n=93 Participants	51.9 years STANDARD_DEVIATION 11.55 • n=4 Participants	52.8 years STANDARD_DEVIATION 11.01 • n=27 Participants
Age, Customized < 65 years	30 participants n=93 Participants	34 participants n=4 Participants	64 participants n=27 Participants
Age, Customized >/= 65 years	5 participants n=93 Participants	5 participants n=4 Participants	10 participants n=27 Participants
Sex: Female, Male Female	24 Participants n=93 Participants	26 Participants n=4 Participants	50 Participants n=27 Participants
Sex: Female, Male Male	11 Participants n=93 Participants	13 Participants n=4 Participants	24 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, Month 12

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug. Last observation carried forward (LOCF): missing responses were imputed by carrying forward the last non-missing post-baseline observation.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants With No Radiographic Progression at Month 12	62.9 percentage of participants	61.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug (nonresponder imputation).

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants With No Radiographic Progression at Month 6 and Month 24 Month 6	68.6 percentage of participants	71.8 percentage of participants
Percentage of Participants With No Radiographic Progression at Month 6 and Month 24 Month 24	51.4 percentage of participants	46.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug; n=number of participants with an assessment at Baseline and given timepoint (observed cases).

The mTSS is a measure of change in joint health: digitized images of radiographs of hands and feet obtained at Screening and Month 12 were scored in a blinded manner. Joints were scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 \[normal\] to 398 \[maximal disease\]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in mTSS at Months 6, 12 and 24 Month 6; n=34, 36	0.88 units on a scale Standard Error 0.273	0.02 units on a scale Standard Error 0.266
Change From Baseline in mTSS at Months 6, 12 and 24 Month 12; n=30, 34	1.62 units on a scale Standard Error 0.486	0.16 units on a scale Standard Error 0.457
Change From Baseline in mTSS at Months 6, 12 and 24 Month 24; n=28, 21	2.24 units on a scale Standard Error 0.912	0.01 units on a scale Standard Error 1.055

SECONDARY outcome

Timeframe: Month 12

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug ith an assessment (nonresponder imputation).

Radiographic progression was defined as a change from Baseline in mTSS that is ≥ 5 units. The mTSS is a measure of change in joint health: digitized images of radiographs of hands and feet obtained at Screening and Month 12 were scored in a blinded manner. Joints were scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 \[normal\] to 398 \[maximal disease\]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

Outcome measures

Outcome measures
Measure	Standard of Care n=34 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants With Rapid Radiographic Progression at Month 12	14.3 percentage of participants	2.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug (nonresponder imputation).

A participant is an ACR20 responder if the following 3 criteria for improvement from Baseline are met: * ≥ 20% improvement in tender joint count; * ≥ 20% improvement in swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: - * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Disability Index of the Health Assessment Questionnaire * Acute phase reactant (erythrocyte sedimentation rate/C-reactive protein \[CRP\]).

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Months 3, 6, 9, 12, 18 and 24 Month 3	57.1 percentage of participants	69.2 percentage of participants
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Months 3, 6, 9, 12, 18 and 24 Month 6	37.1 percentage of participants	64.1 percentage of participants
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Months 3, 6, 9, 12, 18 and 24 Month 9	60.0 percentage of participants	66.7 percentage of participants
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Months 3, 6, 9, 12, 18 and 24 Month 12	68.6 percentage of participants	56.4 percentage of participants
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Months 3, 6, 9, 12, 18 and 24 Month 18	65.7 percentage of participants	51.3 percentage of participants
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Months 3, 6, 9, 12, 18 and 24 Month 24	65.7 percentage of participants	46.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug (nonresponder imputation).

A participant is an ACR50 responder if the following 3 criteria for improvement from Baseline are met: * ≥ 50% improvement in tender joint count; * ≥ 50% improvement in swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Disability Index of the Health Assessment Questionnaire * Acute phase reactant (erythrocyte sedimentation rate/CRP).

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants With American College of Rheumatology 50% (ACR50) Response at Months 3, 6, 9, 12, 18 and 24 Month 3	22.9 percentage of participants	38.5 percentage of participants
Percentage of Participants With American College of Rheumatology 50% (ACR50) Response at Months 3, 6, 9, 12, 18 and 24 Month 6	22.9 percentage of participants	43.6 percentage of participants
Percentage of Participants With American College of Rheumatology 50% (ACR50) Response at Months 3, 6, 9, 12, 18 and 24 Month 9	40.0 percentage of participants	48.7 percentage of participants
Percentage of Participants With American College of Rheumatology 50% (ACR50) Response at Months 3, 6, 9, 12, 18 and 24 Month 12	34.3 percentage of participants	43.6 percentage of participants
Percentage of Participants With American College of Rheumatology 50% (ACR50) Response at Months 3, 6, 9, 12, 18 and 24 Month 18	45.7 percentage of participants	38.5 percentage of participants
Percentage of Participants With American College of Rheumatology 50% (ACR50) Response at Months 3, 6, 9, 12, 18 and 24 Month 24	42.9 percentage of participants	33.3 percentage of participants

SECONDARY outcome

Timeframe: Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug (nonresponder imputation).

A participant is an ACR70 responder if the following 3 criteria for improvement from Baseline are met: * ≥ 70% improvement in tender joint count; * ≥ 70% improvement in swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: - * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Disability Index of the Health Assessment Questionnaire * Acute phase reactant (erythrocyte sedimentation rate/CRP).

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants With American College of Rheumatology 70% (ACR70) Response at Months 3, 6, 9, 12, 18 and 24 Month 12	14.3 percentage of participants	30.8 percentage of participants
Percentage of Participants With American College of Rheumatology 70% (ACR70) Response at Months 3, 6, 9, 12, 18 and 24 Month 18	20.0 percentage of participants	30.8 percentage of participants
Percentage of Participants With American College of Rheumatology 70% (ACR70) Response at Months 3, 6, 9, 12, 18 and 24 Month 3	2.9 percentage of participants	15.4 percentage of participants
Percentage of Participants With American College of Rheumatology 70% (ACR70) Response at Months 3, 6, 9, 12, 18 and 24 Month 6	8.6 percentage of participants	28.2 percentage of participants
Percentage of Participants With American College of Rheumatology 70% (ACR70) Response at Months 3, 6, 9, 12, 18 and 24 Month 9	22.9 percentage of participants	25.6 percentage of participants
Percentage of Participants With American College of Rheumatology 70% (ACR70) Response at Months 3, 6, 9, 12, 18 and 24 Month 24	40.0 percentage of participants	23.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug with an assessment. LOCF: missing responses were imputed by carrying forward the last non-missing post-baseline observation.

Sixty-six joints were assessed and classified as swollen/not swollen by pressure and joint manipulation on physical examination. The presence of swelling is scored 1 and no swelling is 0; range of score is 0-66, with higher scores indicating more swollen joints.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Swollen Joint Count 66 at Months 3, 6, 9, 12, 18 and 24 Month 3	-5.6 swollen joints Standard Error 0.85	-9.2 swollen joints Standard Error 0.81
Change From Baseline in Swollen Joint Count 66 at Months 3, 6, 9, 12, 18 and 24 Month 6	-5.9 swollen joints Standard Error 0.81	-10.4 swollen joints Standard Error 0.78
Change From Baseline in Swollen Joint Count 66 at Months 3, 6, 9, 12, 18 and 24 Month 9	-8.1 swollen joints Standard Error 0.84	-10.8 swollen joints Standard Error 0.80
Change From Baseline in Swollen Joint Count 66 at Months 3, 6, 9, 12, 18 and 24 Month 12	-9.2 swollen joints Standard Error 0.69	-11.3 swollen joints Standard Error 0.66
Change From Baseline in Swollen Joint Count 66 at Months 3, 6, 9, 12, 18 and 24 Month 18	-9.4 swollen joints Standard Error 1.14	-10.0 swollen joints Standard Error 1.09
Change From Baseline in Swollen Joint Count 66 at Months 3, 6, 9, 12, 18 and 24 Month 24	-10.1 swollen joints Standard Error 0.83	-10.6 swollen joints Standard Error 0.80

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Twenty-eight joints were assessed and classified as swollen/not swollen by pressure and joint manipulation on physical examination. The presence of swelling is scored 1 and no swelling is 0; range of score is 0-28, with higher scores indicating more swollen joints.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Swollen Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 3	-4.6 swollen joints Standard Error 0.64	-6.5 swollen joints Standard Error 0.62
Change From Baseline in Swollen Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 6	-4.5 swollen joints Standard Error 0.57	-7.9 swollen joints Standard Error 0.55
Change From Baseline in Swollen Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 9	-6.1 swollen joints Standard Error 0.58	-8.3 swollen joints Standard Error 0.56
Change From Baseline in Swollen Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 12	-6.9 swollen joints Standard Error 0.51	-8.5 swollen joints Standard Error 0.49
Change From Baseline in Swollen Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 18	-7.4 swollen joints Standard Error 0.68	-8.1 swollen joints Standard Error 0.65
Change From Baseline in Swollen Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 24	-7.6 swollen joints Standard Error 0.55	-8.4 swollen joints Standard Error 0.53

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Sixty-eight joints were assessed and classified as tender/not tender by pressure and joint manipulation on physical examination. The presence of tenderness is scored 1 and no tenderness is 0; range of score is 0-68, with higher scores indicating more tender joints.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Tender Joint Count 68 at Months 3, 6, 9, 12, 18 and 24 Month 6	-8.3 tender joints Standard Error 1.38	-15.5 tender joints Standard Error 1.33
Change From Baseline in Tender Joint Count 68 at Months 3, 6, 9, 12, 18 and 24 Month 3	-9.3 tender joints Standard Error 1.63	-12.1 tender joints Standard Error 1.56
Change From Baseline in Tender Joint Count 68 at Months 3, 6, 9, 12, 18 and 24 Month 9	-11.2 tender joints Standard Error 1.35	-15.0 tender joints Standard Error 1.30
Change From Baseline in Tender Joint Count 68 at Months 3, 6, 9, 12, 18 and 24 Month 12	-13.4 tender joints Standard Error 1.41	-14.1 tender joints Standard Error 1.35
Change From Baseline in Tender Joint Count 68 at Months 3, 6, 9, 12, 18 and 24 Month 18	-13.4 tender joints Standard Error 1.67	-13.9 tender joints Standard Error 1.60
Change From Baseline in Tender Joint Count 68 at Months 3, 6, 9, 12, 18 and 24 Month 24	-15.0 tender joints Standard Error 1.32	-15.8 tender joints Standard Error 1.27

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Twenty-eight joints were assessed and classified as tender/not tender by pressure and joint manipulation on physical examination. The presence of tenderness is scored 1 and no tenderness is 0; range of score is 0-28, with higher scores indicating more tender joints.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Tender Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 3	-5.5 tender joints Standard Error 0.93	-7.4 tender joints Standard Error 0.90
Change From Baseline in Tender Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 6	-5.7 tender joints Standard Error 0.78	-9.7 tender joints Standard Error 0.74
Change From Baseline in Tender Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 9	-7.1 tender joints Standard Error 0.86	-9.6 tender joints Standard Error 0.83
Change From Baseline in Tender Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 12	-8.4 tender joints Standard Error 0.82	-9.2 tender joints Standard Error 0.79
Change From Baseline in Tender Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 18	-8.5 tender joints Standard Error 0.94	-9.1 tender joints Standard Error 0.90
Change From Baseline in Tender Joint Count 28 at Months 3, 6, 9, 12, 18 and 24 Month 24	-9.4 tender joints Standard Error 0.80	-10.2 tender joints Standard Error 0.77

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Physicians were asked to indicate the participant's disease activity (independent of the participant's self assessment) on a visual analogue scale (VAS) from 0 (very good) to 100 (very bad). A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Physician's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 3	-29.3 units on a scale Standard Error 3.66	-41.6 units on a scale Standard Error 3.51
Change From Baseline in Physician's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 6	-22.5 units on a scale Standard Error 4.25	-48.0 units on a scale Standard Error 4.08
Change From Baseline in Physician's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 9	-39.6 units on a scale Standard Error 4.21	-48.9 units on a scale Standard Error 4.04
Change From Baseline in Physician's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 12	-43.8 units on a scale Standard Error 4.12	-47.3 units on a scale Standard Error 3.96
Change From Baseline in Physician's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 18	-45.5 units on a scale Standard Error 4.29	-46.2 units on a scale Standard Error 4.12
Change From Baseline in Physician's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 24	-47.6 units on a scale Standard Error 4.23	-47.7 units on a scale Standard Error 4.06

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Participants were asked to indicate how they were doing with their RA on a VAS from 0 (very well) to 100 (very poorly). A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Patient's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 3	-19.5 units on a scale Standard Error 3.58	-21.8 units on a scale Standard Error 3.43
Change From Baseline in Patient's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 6	-14.4 units on a scale Standard Error 4.05	-19.6 units on a scale Standard Error 3.88
Change From Baseline in Patient's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 9	-25.4 units on a scale Standard Error 4.02	-20.2 units on a scale Standard Error 3.86
Change From Baseline in Patient's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 12	-22.4 units on a scale Standard Error 3.81	-22.3 units on a scale Standard Error 3.65
Change From Baseline in Patient's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 18	-29.4 units on a scale Standard Error 3.86	-23.0 units on a scale Standard Error 3.71
Change From Baseline in Patient's Global Assessment of Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 24	-30.6 units on a scale Standard Error 3.99	-23.6 units on a scale Standard Error 3.83

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Participants were asked to indicate how severe their pain had been in the previous week on a VAS from 0 (no pain) to 100 (pain as bad as it could be). A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Patient's Global Assessment of Pain at Months 3, 6, 9, 12, 18 and 24 Month 3	-22.0 units on a scale Standard Error 3.79	-23.0 units on a scale Standard Error 3.64
Change From Baseline in Patient's Global Assessment of Pain at Months 3, 6, 9, 12, 18 and 24 Month 6	-14.5 units on a scale Standard Error 3.94	-23.0 units on a scale Standard Error 3.78
Change From Baseline in Patient's Global Assessment of Pain at Months 3, 6, 9, 12, 18 and 24 Month 9	-21.7 units on a scale Standard Error 4.03	-21.3 units on a scale Standard Error 3.87
Change From Baseline in Patient's Global Assessment of Pain at Months 3, 6, 9, 12, 18 and 24 Month 12	-22.0 units on a scale Standard Error 4.01	-24.4 units on a scale Standard Error 3.85
Change From Baseline in Patient's Global Assessment of Pain at Months 3, 6, 9, 12, 18 and 24 Month 18	-28.1 units on a scale Standard Error 4.07	-22.7 units on a scale Standard Error 3.90
Change From Baseline in Patient's Global Assessment of Pain at Months 3, 6, 9, 12, 18 and 24 Month 24	-26.6 units on a scale Standard Error 4.40	-23.6 units on a scale Standard Error 4.22

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in CRP at Months 3, 6, 9, 12, 18 and 24 Month 24; n=26, 23	-13.5 mg/L Standard Error 2.46	-11.2 mg/L Standard Error 2.36
Change From Baseline in CRP at Months 3, 6, 9, 12, 18 and 24 Month 3; n=33, 38	-10.2 mg/L Standard Error 2.39	-8.9 mg/L Standard Error 2.23
Change From Baseline in CRP at Months 3, 6, 9, 12, 18 and 24 Month 6; n=34, 38	-7.6 mg/L Standard Error 3.26	-9.1 mg/L Standard Error 3.08
Change From Baseline in CRP at Months 3, 6, 9, 12, 18 and 24 Month 9; n=35, 38	-11.3 mg/L Standard Error 2.84	-11.1 mg/L Standard Error 2.72
Change From Baseline in CRP at Months 3, 6, 9, 12, 18 and 24 Month 12; n=35, 38	-13.7 mg/L Standard Error 2.37	-10.8 mg/L Standard Error 2.28
Change From Baseline in CRP at Months 3, 6, 9, 12, 18 and 24 Month 18; n=35, 38	-15.2 mg/L Standard Error 2.51	-9.7 mg/L Standard Error 2.41

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10, with higher scores indicating higher disease activity.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Disease Activity Score DAS28(CRP) at Months 3, 6, 9, 12, 18 and 24 Month 3; n=33, 38	-1.4 units on a scale Standard Error 0.20	-1.8 units on a scale Standard Error 0.18
Change From Baseline in Disease Activity Score DAS28(CRP) at Months 3, 6, 9, 12, 18 and 24 Month 6; n=34, 38	-1.4 units on a scale Standard Error 0.21	-2.3 units on a scale Standard Error 0.20
Change From Baseline in Disease Activity Score DAS28(CRP) at Months 3, 6, 9, 12, 18 and 24 Month 9; n=35, 38	-2.0 units on a scale Standard Error 0.21	-2.3 units on a scale Standard Error 0.20
Change From Baseline in Disease Activity Score DAS28(CRP) at Months 3, 6, 9, 12, 18 and 24 Month 12; n=35, 38	-2.1 units on a scale Standard Error 0.20	-2.4 units on a scale Standard Error 0.19
Change From Baseline in Disease Activity Score DAS28(CRP) at Months 3, 6, 9, 12, 18 and 24 Month 18; n=35, 38	-2.4 units on a scale Standard Error 0.22	-2.4 units on a scale Standard Error 0.21
Change From Baseline in Disease Activity Score DAS28(CRP) at Months 3, 6, 9, 12, 18 and 24 Month 24; n=35, 38	-2.6 units on a scale Standard Error 0.20	-2.6 units on a scale Standard Error 0.19

SECONDARY outcome

Timeframe: Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug with an assessment (non-responder imputation).

DAS28(CRP) remission was defined as DAS28(CRP) \< 2.6. The DAS28(CRP) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10, with higher scores indicating higher disease activity.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants With DAS28(CRP) Remission at Months 3, 6, 9, 12, 18 and 24 Month 3	8.6 percentage of participants	17.9 percentage of participants
Percentage of Participants With DAS28(CRP) Remission at Months 3, 6, 9, 12, 18 and 24 Month 6	11.4 percentage of participants	35.9 percentage of participants
Percentage of Participants With DAS28(CRP) Remission at Months 3, 6, 9, 12, 18 and 24 Month 9	31.4 percentage of participants	28.2 percentage of participants
Percentage of Participants With DAS28(CRP) Remission at Months 3, 6, 9, 12, 18 and 24 Month 12	22.9 percentage of participants	35.9 percentage of participants
Percentage of Participants With DAS28(CRP) Remission at Months 3, 6, 9, 12, 18 and 24 Month 18	34.3 percentage of participants	30.8 percentage of participants
Percentage of Participants With DAS28(CRP) Remission at Months 3, 6, 9, 12, 18 and 24 Month 24	42.9 percentage of participants	38.5 percentage of participants

SECONDARY outcome

Timeframe: Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug with an assessment (non-responder imputation).

DAS28(CRP) low disease activity was defined as DAS28(CRP) \< 3.2. The DAS28(CRP) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10, with higher scores indicating higher disease activity.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants With DAS28(CRP) Low Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 3	22.9 percentage of participants	33.3 percentage of participants
Percentage of Participants With DAS28(CRP) Low Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 6	28.6 percentage of participants	51.3 percentage of participants
Percentage of Participants With DAS28(CRP) Low Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 9	51.4 percentage of participants	56.4 percentage of participants
Percentage of Participants With DAS28(CRP) Low Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 12	48.6 percentage of participants	56.4 percentage of participants
Percentage of Participants With DAS28(CRP) Low Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 18	51.4 percentage of participants	48.7 percentage of participants
Percentage of Participants With DAS28(CRP) Low Disease Activity at Months 3, 6, 9, 12, 18 and 24 Month 24	54.3 percentage of participants	43.6 percentage of participants

SECONDARY outcome

Timeframe: Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug with an assessment (non-responder imputation).

A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS28 score. The DAS28 score ranges from 0-10, with higher scores indicating more disease activity. A Good EULAR Response is defined as an improvement (decrease) in the DAS28 of ≥ 1.2 compared with Baseline and attainment of a DAS28 score of ≤ 3.2.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Months 3, 6, 9, 12, 18 and 24 Month 3	22.9 percentage of participants	30.8 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Months 3, 6, 9, 12, 18 and 24 Month 6	28.6 percentage of participants	48.7 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Months 3, 6, 9, 12, 18 and 24 Month 9	48.6 percentage of participants	51.3 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Months 3, 6, 9, 12, 18 and 24 Month 12	45.7 percentage of participants	53.8 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Months 3, 6, 9, 12, 18 and 24 Month 18	51.4 percentage of participants	48.7 percentage of participants
Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Months 3, 6, 9, 12, 18 and 24 Month 24	54.3 percentage of participants	43.6 percentage of participants

SECONDARY outcome

Timeframe: Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug with an assessment (non-responder imputation).

A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS28 score. The DAS28 score ranges from 0-10, with higher scores indicating more disease activity. A Moderate EULAR Response is defined as either: an improvement (decrease) in the DAS28 of \> 0.6 and \< 1.2 from Baseline and attainment of a DAS28 score of ≤ 5.1; or an improvement (decrease) in the DAS28 of ≥ 1.2 from Baseline and attainment of a DAS28 score of \> 3.2.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants With EULAR Moderate Response at Months 3, 6, 9, 12, 18 and 24 Month 3	37.1 percentage of participants	48.7 percentage of participants
Percentage of Participants With EULAR Moderate Response at Months 3, 6, 9, 12, 18 and 24 Month 6	25.7 percentage of participants	30.8 percentage of participants
Percentage of Participants With EULAR Moderate Response at Months 3, 6, 9, 12, 18 and 24 Month 9	28.6 percentage of participants	28.2 percentage of participants
Percentage of Participants With EULAR Moderate Response at Months 3, 6, 9, 12, 18 and 24 Month 12	37.1 percentage of participants	23.1 percentage of participants
Percentage of Participants With EULAR Moderate Response at Months 3, 6, 9, 12, 18 and 24 Month 18	22.9 percentage of participants	10.3 percentage of participants
Percentage of Participants With EULAR Moderate Response at Months 3, 6, 9, 12, 18 and 24 Month 24	14.3 percentage of participants	10.3 percentage of participants

SECONDARY outcome

Timeframe: Month 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug and had an assessment.

Percentage of participants with a flare-up after remission by Month 24, defined as participants who reached remission (DAS28 \< 2.6) but later had two consecutive visits with DAS28 ≥ 2.6 (based on observed cases only). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10, with higher scores indicating higher disease activity.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants With Flare-Up After Remission by Month 24	8.6 percentage of participants	15.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

HAQ is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A lower HAQ-DI score is better.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Disability Index of the Health Assessment Questionnaire (HAQ-DI) at Months 3, 6, 9, 12, 18 and 24 Month 3	-0.41 units on a scale Standard Error 0.094	-0.38 units on a scale Standard Error 0.090
Change From Baseline in Disability Index of the Health Assessment Questionnaire (HAQ-DI) at Months 3, 6, 9, 12, 18 and 24 Month 6	-0.29 units on a scale Standard Error 0.095	-0.46 units on a scale Standard Error 0.092
Change From Baseline in Disability Index of the Health Assessment Questionnaire (HAQ-DI) at Months 3, 6, 9, 12, 18 and 24 Month 9	-0.52 units on a scale Standard Error 0.095	-0.50 units on a scale Standard Error 0.092
Change From Baseline in Disability Index of the Health Assessment Questionnaire (HAQ-DI) at Months 3, 6, 9, 12, 18 and 24 Month 12	-0.60 units on a scale Standard Error 0.093	-0.50 units on a scale Standard Error 0.089
Change From Baseline in Disability Index of the Health Assessment Questionnaire (HAQ-DI) at Months 3, 6, 9, 12, 18 and 24 Month 18	-0.60 units on a scale Standard Error 0.102	-0.55 units on a scale Standard Error 0.098
Change From Baseline in Disability Index of the Health Assessment Questionnaire (HAQ-DI) at Months 3, 6, 9, 12, 18 and 24 Month 24	-0.61 units on a scale Standard Error 0.107	-0.53 units on a scale Standard Error 0.102

SECONDARY outcome

Timeframe: Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug with an assessment (non-responder imputation).

The percentage of participants achieving MCID in HAQ, defined as a 0.22 unit decrease in HAQ. HAQ is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A lower HAQ-DI score is better.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants Achieving Minimal Clinical Important Difference (MCID) in HAQ at Months 3, 6, 9, 12, 18 and 24 Month 3	65.7 percentage of participants	53.8 percentage of participants
Percentage of Participants Achieving Minimal Clinical Important Difference (MCID) in HAQ at Months 3, 6, 9, 12, 18 and 24 Month 6	54.3 percentage of participants	51.3 percentage of participants
Percentage of Participants Achieving Minimal Clinical Important Difference (MCID) in HAQ at Months 3, 6, 9, 12, 18 and 24 Month 9	57.1 percentage of participants	64.1 percentage of participants
Percentage of Participants Achieving Minimal Clinical Important Difference (MCID) in HAQ at Months 3, 6, 9, 12, 18 and 24 Month 12	68.6 percentage of participants	59.0 percentage of participants
Percentage of Participants Achieving Minimal Clinical Important Difference (MCID) in HAQ at Months 3, 6, 9, 12, 18 and 24 Month 18	57.1 percentage of participants	53.8 percentage of participants
Percentage of Participants Achieving Minimal Clinical Important Difference (MCID) in HAQ at Months 3, 6, 9, 12, 18 and 24 Month 24	57.1 percentage of participants	41.0 percentage of participants

SECONDARY outcome

Timeframe: Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug with an assessment (non-responder imputation).

The percentage of participants achieving HAQ \< 0.5. HAQ is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. HAQ remission indicating normal physical function is defined by HAQ-DI \< 0.5. A lower HAQ-DI score is better.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants Achieving HAQ < 0.5 at Months 3, 6, 9, 12, 18 and 24 Month 3	31.4 percentage of participants	20.5 percentage of participants
Percentage of Participants Achieving HAQ < 0.5 at Months 3, 6, 9, 12, 18 and 24 Month 6	22.9 percentage of participants	30.8 percentage of participants
Percentage of Participants Achieving HAQ < 0.5 at Months 3, 6, 9, 12, 18 and 24 Month 9	34.3 percentage of participants	35.9 percentage of participants
Percentage of Participants Achieving HAQ < 0.5 at Months 3, 6, 9, 12, 18 and 24 Month 12	34.3 percentage of participants	33.3 percentage of participants
Percentage of Participants Achieving HAQ < 0.5 at Months 3, 6, 9, 12, 18 and 24 Month 18	28.6 percentage of participants	30.8 percentage of participants
Percentage of Participants Achieving HAQ < 0.5 at Months 3, 6, 9, 12, 18 and 24 Month 24	28.6 percentage of participants	30.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days. Participants respond to the questions on a scale from 'not at all' (0) to 'very much' (4). The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 3	7.1 units on a scale Standard Error 1.62	8.0 units on a scale Standard Error 1.56
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 6	5.4 units on a scale Standard Error 1.77	8.2 units on a scale Standard Error 1.70
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 9	9.5 units on a scale Standard Error 1.70	8.0 units on a scale Standard Error 1.63
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 12	10.7 units on a scale Standard Error 1.80	8.0 units on a scale Standard Error 1.73
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 18	10.2 units on a scale Standard Error 1.98	8.2 units on a scale Standard Error 1.90
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 24	9.8 units on a scale Standard Error 2.00	8.8 units on a scale Standard Error 1.92

SECONDARY outcome

Timeframe: Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug with an assessment (non-responder imputation).

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Percentage of Participants Achieving MCID in FACIT-Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 3	14.3 percentage of participants	13.2 percentage of participants
Percentage of Participants Achieving MCID in FACIT-Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 6	14.3 percentage of participants	7.9 percentage of participants
Percentage of Participants Achieving MCID in FACIT-Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 9	17.1 percentage of participants	5.3 percentage of participants
Percentage of Participants Achieving MCID in FACIT-Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 12	8.6 percentage of participants	13.2 percentage of participants
Percentage of Participants Achieving MCID in FACIT-Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 18	8.6 percentage of participants	15.8 percentage of participants
Percentage of Participants Achieving MCID in FACIT-Fatigue Scale at Months 3, 6, 9, 12, 18 and 24 Month 24	11.4 percentage of participants	5.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug. LOCF: missing responses were imputed by carrying forward the last non-missing post-baseline observation; n=number of participants with an assessment at given time point.

The WLQ was used to measure the impairment in work-related productivity, with reference to the previous two weeks. Each work-related question is scored from 0 to 4 and the total score ranges from 0-100, with lower scores signifying fewer limitations at work.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Work Limitations Questionnaire (WLQ) at Months 3, 6, 9, 12, 18 and 24 Month 9; n=25, 25	-8.4 units on a scale Standard Error 4.45	-11.8 units on a scale Standard Error 4.45
Change From Baseline in Work Limitations Questionnaire (WLQ) at Months 3, 6, 9, 12, 18 and 24 Month 12; n=25, 25	-15.2 units on a scale Standard Error 4.05	-11.8 units on a scale Standard Error 4.05
Change From Baseline in Work Limitations Questionnaire (WLQ) at Months 3, 6, 9, 12, 18 and 24 Month 18; n=25, 25	-15.6 units on a scale Standard Error 4.51	-12.8 units on a scale Standard Error 4.51
Change From Baseline in Work Limitations Questionnaire (WLQ) at Months 3, 6, 9, 12, 18 and 24 Month 24; n=25, 25	-13.7 units on a scale Standard Error 4.34	-12.6 units on a scale Standard Error 4.34
Change From Baseline in Work Limitations Questionnaire (WLQ) at Months 3, 6, 9, 12, 18 and 24 Month 3; n=23, 24	-7.0 units on a scale Standard Error 4.18	-11.5 units on a scale Standard Error 4.10
Change From Baseline in Work Limitations Questionnaire (WLQ) at Months 3, 6, 9, 12, 18 and 24 Month 6; n=24, 25	-6.1 units on a scale Standard Error 4.20	-13.9 units on a scale Standard Error 4.11

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

The EQ-5D is a participant answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that essentially attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.594 to 1 (with higher scores indicating better health state).

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in EuroQOL Questionnaire (EQ-5D) Index Score at Months 3, 6, 9, 12, 18 and 24 Month 3; n=34, 34	0.21 units on a scale Standard Error 0.041	0.22 units on a scale Standard Error 0.041
Change From Baseline in EuroQOL Questionnaire (EQ-5D) Index Score at Months 3, 6, 9, 12, 18 and 24 Month 6; n=35, 36	0.18 units on a scale Standard Error 0.044	0.23 units on a scale Standard Error 0.044
Change From Baseline in EuroQOL Questionnaire (EQ-5D) Index Score at Months 3, 6, 9, 12, 18 and 24 Month 9; n=35, 36	0.26 units on a scale Standard Error 0.044	0.22 units on a scale Standard Error 0.044
Change From Baseline in EuroQOL Questionnaire (EQ-5D) Index Score at Months 3, 6, 9, 12, 18 and 24 Month 12; n=35, 36	0.25 units on a scale Standard Error 0.040	0.26 units on a scale Standard Error 0.040
Change From Baseline in EuroQOL Questionnaire (EQ-5D) Index Score at Months 3, 6, 9, 12, 18 and 24 Month 18; n=35, 36	0.25 units on a scale Standard Error 0.045	0.24 units on a scale Standard Error 0.045
Change From Baseline in EuroQOL Questionnaire (EQ-5D) Index Score at Months 3, 6, 9, 12, 18 and 24 Month 24; n=35, 36	0.26 units on a scale Standard Error 0.049	0.22 units on a scale Standard Error 0.049

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

Population: Intent-to-treat population: all participants who were randomized and received at least one dose of study drug and had an assessment. LOCF: missing responses were imputed by carrying forward the last non-missing post-baseline observation.

The EQ-5D VAS records the participant's self-rated health on a scale from 0-100 where 100 is the 'best imaginable health state' and 0 is the 'worst imaginable health state.'

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in EQ-5D VAS at Months 3, 6, 9, 12, 18 and 24 Month 3	18.7 units on a scale Standard Error 3.18	16.2 units on a scale Standard Error 3.05
Change From Baseline in EQ-5D VAS at Months 3, 6, 9, 12, 18 and 24 Month 6	10.7 units on a scale Standard Error 3.70	18.6 units on a scale Standard Error 3.55
Change From Baseline in EQ-5D VAS at Months 3, 6, 9, 12, 18 and 24 Month 9	20.1 units on a scale Standard Error 3.78	17.7 units on a scale Standard Error 3.63
Change From Baseline in EQ-5D VAS at Months 3, 6, 9, 12, 18 and 24 Month 12	22.2 units on a scale Standard Error 3.46	19.5 units on a scale Standard Error 3.32
Change From Baseline in EQ-5D VAS at Months 3, 6, 9, 12, 18 and 24 Month 18	22.3 units on a scale Standard Error 3.62	21.2 units on a scale Standard Error 3.47
Change From Baseline in EQ-5D VAS at Months 3, 6, 9, 12, 18 and 24 Month 24	22.1 units on a scale Standard Error 4.11	19.7 units on a scale Standard Error 3.95

SECONDARY outcome

Timeframe: Baseline, Months 3, 6, 9, 12, 18, 24

BDI is a 21-item questionnaire, participant self-report rating inventory that measures characteristic attitudes and symptoms of depression. The range of scores is 0 to 63, with a higher value representing a worse outcome.

Outcome measures

Outcome measures
Measure	Standard of Care n=33 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Months 3, 6, 9, 12, 18 and 24 Month 3	-4.3 units on a scale Standard Error 1.15	-3.1 units on a scale Standard Error 1.07
Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Months 3, 6, 9, 12, 18 and 24 Month 6	-1.0 units on a scale Standard Error 1.28	-2.4 units on a scale Standard Error 1.19
Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Months 3, 6, 9, 12, 18 and 24 Month 9	-4.3 units on a scale Standard Error 1.04	-3.7 units on a scale Standard Error 0.97
Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Months 3, 6, 9, 12, 18 and 24 Month 12	-5.1 units on a scale Standard Error 1.24	-3.5 units on a scale Standard Error 1.15
Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Months 3, 6, 9, 12, 18 and 24 Month 18	-4.8 units on a scale Standard Error 1.22	-3.5 units on a scale Standard Error 1.14
Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Months 3, 6, 9, 12, 18 and 24 Month 24	-4.8 units on a scale Standard Error 1.15	-3.4 units on a scale Standard Error 1.07

SECONDARY outcome

Timeframe: Months 3, 6, 9, 12, 18, 24

Participants measured their satisfaction with care by specifying their in response to the question "How satisfied are you with the results of your RA treatment?" on a 5-point Likert scale, from the following 5 answers: not satisfied, a little satisfied, moderately satisfied, well satisfied, very well satisfied. Scores range from 1 to 5, with higher scores indicating more satisfaction with their care.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=38 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Likert Scale for Participant's Satisfaction With Care at Months 3, 6, 9, 12, 18 and 24 Month 3	3.5 units on a scale Standard Error 0.20	4.1 units on a scale Standard Error 0.19
Likert Scale for Participant's Satisfaction With Care at Months 3, 6, 9, 12, 18 and 24 Month 6	3.3 units on a scale Standard Error 0.19	4.1 units on a scale Standard Error 0.18
Likert Scale for Participant's Satisfaction With Care at Months 3, 6, 9, 12, 18 and 24 Month 9	3.7 units on a scale Standard Error 0.17	4.1 units on a scale Standard Error 0.17
Likert Scale for Participant's Satisfaction With Care at Months 3, 6, 9, 12, 18 and 24 Month 12	3.9 units on a scale Standard Error 0.16	4.2 units on a scale Standard Error 0.15
Likert Scale for Participant's Satisfaction With Care at Months 3, 6, 9, 12, 18 and 24 Month 18	4.2 units on a scale Standard Error 0.17	4.2 units on a scale Standard Error 0.16
Likert Scale for Participant's Satisfaction With Care at Months 3, 6, 9, 12, 18 and 24 Month 24	4.1 units on a scale Standard Error 0.16	4.3 units on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline

Population: Intent-to-treat population: all participants who were randomized, received at least one dose of study drug, and had an assessment. n=the number of participants included in the percentage calculation (n=25, 28 is the number of participants who answered that they did have health insurance).

The HCR consists of four aspects: medical insurance, health care for RA in the past 4 weeks, hospitalization in the past 4 weeks, and out of pocket expenses incurred for the current study condition. Participants were asked whether and what type of health insurance they had. Types of Canadian insurance included: Régie de l'assurance maladie du Québec (RAMQ); Société de l'assurance automobile du Québec (SAAQ); Commission de la santé et de la sécurité du travail (CSST); Canadian Health Insurance Program (CHIP); and L'indemnisation des victimes d'actes criminals (IVAC).

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Health Care Resources Questionnaire (HCR): Medical Insurance at Baseline Has health insurance; n=35, 39	71.4 percentage of participants	71.8 percentage of participants
Health Care Resources Questionnaire (HCR): Medical Insurance at Baseline 1 insurance; n=35, 39	71.4 percentage of participants	66.7 percentage of participants
Health Care Resources Questionnaire (HCR): Medical Insurance at Baseline >/= 1 insurance; n=35, 39	0 percentage of participants	2.6 percentage of participants
Health Care Resources Questionnaire (HCR): Medical Insurance at Baseline RMAQ; n=25, 28	4.0 percentage of participants	3.6 percentage of participants
Health Care Resources Questionnaire (HCR): Medical Insurance at Baseline SAAQ; n=25, 28	0 percentage of participants	0 percentage of participants
Health Care Resources Questionnaire (HCR): Medical Insurance at Baseline Federal government; n=25, 28	0 percentage of participants	3.6 percentage of participants
Health Care Resources Questionnaire (HCR): Medical Insurance at Baseline CSST; n=25, 28	0 percentage of participants	0 percentage of participants
Health Care Resources Questionnaire (HCR): Medical Insurance at Baseline OHIP; n=25, 28	12.0 percentage of participants	21.4 percentage of participants
Health Care Resources Questionnaire (HCR): Medical Insurance at Baseline IVAC; n=25, 28	0 percentage of participants	0 percentage of participants
Health Care Resources Questionnaire (HCR): Medical Insurance at Baseline Blue Cross; n=25, 28	20.0 percentage of participants	7.1 percentage of participants
Health Care Resources Questionnaire (HCR): Medical Insurance at Baseline Other; n=25, 28	64.0 percentage of participants	64.3 percentage of participants

SECONDARY outcome

Timeframe: Final Visit (up to Month 24)

Population: Intent-to-treat population: all participants who were randomized, received at least one dose of study drug, and had an assessment. n=the number of participants included in the percentage calculation (n=26, 26 is the number of participants who answered that they did have health insurance).

Outcome measures

Outcome measures
Measure	Standard of Care n=33 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=37 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
HCR: Medical Insurance at Final Visit Has health insurance; n=33, 37	78.8 percentage of participants	70.3 percentage of participants
HCR: Medical Insurance at Final Visit 1 insurance; n=33, 37	78.8 percentage of participants	70.3 percentage of participants
HCR: Medical Insurance at Final Visit >/= 1 insurance; n=33, 37	0 percentage of participants	0 percentage of participants
HCR: Medical Insurance at Final Visit RMAQ; n=26, 26	0 percentage of participants	3.8 percentage of participants
HCR: Medical Insurance at Final Visit SAAQ; n=26, 26	0 percentage of participants	0 percentage of participants
HCR: Medical Insurance at Final Visit Federal government; n=26, 26	0 percentage of participants	3.8 percentage of participants
HCR: Medical Insurance at Final Visit CSST; n=26, 26	0 percentage of participants	0 percentage of participants
HCR: Medical Insurance at Final Visit OHIP; n=26, 26	11.5 percentage of participants	11.5 percentage of participants
HCR: Medical Insurance at Final Visit IVAC; n=26, 26	0 percentage of participants	0 percentage of participants
HCR: Medical Insurance at Final Visit Blue Cross; n=26, 26	11.5 percentage of participants	7.7 percentage of participants
HCR: Medical Insurance at Final Visit Other; n=26, 26	76.9 percentage of participants	73.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline

Population: Intent-to-treat population: all participants who were randomized, received at least one dose of study drug, and had an assessment. n=the number of participants included in the percentage calculation (n=11, 10 is the number of participants who stated that they had used healthcare for RA in the past 4 weeks).

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
HCR: Health Care for RA in the Past 4 Weeks at Baseline Used health care in past 4 weeks; n=35, 39	34.1 percentage of participants	25.6 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Baseline Unscheduled visits to study doctor; n=11, 10	27.3 percentage of participants	20.0 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Baseline Visits to another physician; n=11, 10	27.3 percentage of participants	0 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Baseline Visits to a healthcare professional; n=11, 10	9.1 percentage of participants	20.0 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Baseline Visit to hospital emergency room; n=11, 10	0 percentage of participants	10.0 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Baseline Use of an ambulance service; n=11, 10	0 percentage of participants	0 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Baseline Complementary/alternative therapy visits; n=11, 10	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Final Visit (up to Month 24)

Population: Intent-to-treat population: all participants who were randomized, received at least one dose of study drug, and had an assessment. n=the number of participants included in the percentage calculation (n=2, 3 is the number of participants who stated that they had used healthcare for RA in the past 4 weeks).

Outcome measures

Outcome measures
Measure	Standard of Care n=33 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=37 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
HCR: Health Care for RA in the Past 4 Weeks at Final Visit Visits to a healthcare professional; n=2, 3	50.0 percentage of participants	33.3 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Final Visit Used health care in past 4 weeks; n=33, 37	6.1 percentage of participants	8.1 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Final Visit Unscheduled visits to study doctor; n=2, 3	0 percentage of participants	0 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Final Visit Visits to another physician; n=2, 3	0 percentage of participants	33.3 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Final Visit Visit to hospital emergency room; n=2, 3	0 percentage of participants	33.3 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Final Visit Use of an ambulance service; n=2, 3	0 percentage of participants	0 percentage of participants
HCR: Health Care for RA in the Past 4 Weeks at Final Visit Complementary/alternative therapy visits; n=2, 3	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline

Population: Intent-to-treat population: all participants who were randomized, received at least one dose of study drug, and had an assessment. n=participants with non-zero expenses for given category, and included in the mean (SD) calculation.

The HCR consists of four aspects: medical insurance, health care for RA in the past 4 weeks, hospitalization in the past 4 weeks, and out of pocket expenses incurred for the current study condition. Participants were asked what type of out-of-pocket expenses they had incurred for their RA in the past 4 weeks. Based on Canadian dollars.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Baseline Over-the-counter medications; n=11, 14	34.2 Canadian dollars Standard Deviation 28.1	60.3 Canadian dollars Standard Deviation 62.82
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Baseline Health care professional payments; n=0, 2	NA Canadian dollars Standard Deviation NA n=0 for this arm	60.0 Canadian dollars Standard Deviation 28.28
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Baseline Medical procedures/laboratory tests; n=0, 0	NA Canadian dollars Standard Deviation NA n=0 for this arm	NA Canadian dollars Standard Deviation NA n=0 for this arm
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Baseline Medical devices; n=2, 2	60.0 Canadian dollars Standard Deviation 56.57	97.5 Canadian dollars Standard Deviation 31.82
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Baseline Healthcare or extra help at home; n=0, 1	NA Canadian dollars Standard Deviation NA n=0 for this arm	80.0 Canadian dollars Standard Deviation NA n=1 for this arm
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Baseline Transportation costs; n=17, 12	36.3 Canadian dollars Standard Deviation 19.53	30.3 Canadian dollars Standard Deviation 18.24

SECONDARY outcome

Timeframe: Final Visit (up to Month 24)

The HCR consists of four aspects: medical insurance, health care for RA in the past 4 weeks, hospitalization in the past 4 weeks, and out of pocket expenses incurred for the current study condition. Participants were asked what type of out-of-pocket expenses they had incurred for their RA in the past 4 weeks. Based on Canadian dollars.

Outcome measures

Outcome measures
Measure	Standard of Care n=35 Participants Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 Participants Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Final Visit Over-the-counter medications; n=7, 7	108.3 Canadian dollars Standard Deviation 78.75	34.4 Canadian dollars Standard Deviation 32.82
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Final Visit Health care professional payments; n=1, 3	45.0 Canadian dollars Standard Deviation NA n=1 for this arm	91.7 Canadian dollars Standard Deviation 43.68
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Final Visit Medical procedures/laboratory tests; n=0, 0	NA Canadian dollars Standard Deviation NA n=0 for this arm	NA Canadian dollars Standard Deviation NA n=0 for this arm
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Final Visit Medical devices; n=0, 0	NA Canadian dollars Standard Deviation NA n=0 for this arm	NA Canadian dollars Standard Deviation NA n=0 for this arm
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Final Visit Healthcare or extra help at home; n=0, 0	NA Canadian dollars Standard Deviation NA n=0 for this arm	NA Canadian dollars Standard Deviation NA n=0 for this arm
HCR: Out of Pocket Expenses Incurred for the Current Study Condition in the Past 4 Weeks at Final Visit Transportation costs; n=4, 4	61.3 Canadian dollars Standard Deviation 40.90	35.0 Canadian dollars Standard Deviation 17.32

Adverse Events

Standard of Care

Serious events: 3 serious events

Other events: 32 other events

Deaths: 0 deaths

Early Adalimumab

Serious events: 4 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Standard of Care n=35 participants at risk Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 participants at risk Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	2.9% 1/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
General disorders SURGICAL FAILURE	0.00% 0/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Infections and infestations HERPES ZOSTER	0.00% 0/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ACUTE MYELOID LEUKAEMIA	0.00% 0/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER	0.00% 0/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LUNG NEOPLASM MALIGNANT	2.9% 1/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Psychiatric disorders PSYCHOTIC DISORDER	2.9% 1/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.

Other adverse events

Additional Information

Global Medical Information

AbbVie

Phone: 800-633-9110

Results disclosure agreements

Principal investigator is a sponsor employee AbbVie 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. AbbVie 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 AbbVie needs to secure patent or proprietary protection.
Publication restrictions are in place

Restriction type: OTHER

Measure	Standard of Care n=35 participants at risk Participants received methotrexate and other disease modifying antirheumatic drugs as per local treatment guidelines and study doctor's judgement. Adalimumab may have been initiated after a minimum of 6 months.	Early Adalimumab n=39 participants at risk Participants received 40 mg of adalimumab administered subcutaneously at Baseline and then every other week for 24 months. Participants received a methotrexate regimen based on local guidelines and their study doctor's judgment.
Blood and lymphatic system disorders ANAEMIA	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Cardiac disorders PALPITATIONS	2.9% 1/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Eye disorders DRY EYE	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Eye disorders VISION BLURRED	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Eye disorders VITREOUS FLOATERS	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Gastrointestinal disorders DIARRHOEA	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Gastrointestinal disorders DYSPEPSIA	2.9% 1/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Gastrointestinal disorders MOUTH ULCERATION	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Gastrointestinal disorders NAUSEA	17.1% 6/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Gastrointestinal disorders VOMITING	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
General disorders CHEST PAIN	0.00% 0/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
General disorders CYST	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
General disorders FATIGUE	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	7.7% 3/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
General disorders INJECTION SITE REACTION	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	12.8% 5/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Immune system disorders DRUG HYPERSENSITIVITY	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Infections and infestations CYSTITIS	0.00% 0/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Infections and infestations HERPES ZOSTER	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Infections and infestations INFLUENZA	2.9% 1/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	7.7% 3/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Infections and infestations LOWER RESPIRATORY TRACT INFECTION	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Infections and infestations NASOPHARYNGITIS	20.0% 7/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	20.5% 8/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Infections and infestations ORAL CANDIDIASIS	0.00% 0/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Infections and infestations RESPIRATORY TRACT INFECTION	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Infections and infestations SINUSITIS	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Investigations ALANINE AMINOTRANSFERASE INCREASED	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	15.4% 6/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	15.4% 6/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Investigations BLOOD CHOLESTEROL INCREASED	2.9% 1/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	12.8% 5/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Investigations BLOOD GLUCOSE INCREASED	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Investigations BLOOD TRIGLYCERIDES INCREASED	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	7.7% 3/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Investigations HEPATIC ENZYME INCREASED	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Investigations WEIGHT DECREASED	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Musculoskeletal and connective tissue disorders ARTHRALGIA	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	7.7% 3/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Musculoskeletal and connective tissue disorders BACK PAIN	2.9% 1/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	7.7% 3/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Musculoskeletal and connective tissue disorders JOINT SWELLING	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	7.7% 3/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Musculoskeletal and connective tissue disorders RHEUMATOID ARTHRITIS	22.9% 8/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	25.6% 10/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Musculoskeletal and connective tissue disorders TENDONITIS	2.9% 1/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Nervous system disorders AMNESIA	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Nervous system disorders DIZZINESS	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Nervous system disorders HEADACHE	17.1% 6/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Psychiatric disorders ANXIETY	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Psychiatric disorders DEPRESSION	17.1% 6/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Psychiatric disorders INSOMNIA	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	2.6% 1/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Respiratory, thoracic and mediastinal disorders COUGH	11.4% 4/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	0.00% 0/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	7.7% 3/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Skin and subcutaneous tissue disorders ACNE	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Skin and subcutaneous tissue disorders ALOPECIA	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Skin and subcutaneous tissue disorders DRY SKIN	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	0.00% 0/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Skin and subcutaneous tissue disorders ECCHYMOSIS	0.00% 0/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Skin and subcutaneous tissue disorders ECZEMA	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Skin and subcutaneous tissue disorders RASH	14.3% 5/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	10.3% 4/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Skin and subcutaneous tissue disorders RASH PAPULAR	5.7% 2/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Vascular disorders HOT FLUSH	0.00% 0/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.
Vascular disorders HYPERTENSION	8.6% 3/35 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.	5.1% 2/39 • Baseline through Month 24 (± 10 days) plus 70 days follow-up.