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

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.

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.

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.

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]).

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. The MCID was defined as a 3.56-unit decrease in FACIT-Fatigue Scale.

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.

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).

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.'

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.

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.

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).

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).

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 about their use of health care for RA in the past 4 weeks.

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 about their use of health care for RA in the past 4 weeks.

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.

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.