A Pilot Study of the Feasibility of Discontinuation of Adalimumab in Stable Rheumatoid Arthritis Patients in Clinical Remission (ADMIRE)

有源比较器：Adalimumab + MTX

Participants continued treatment with adalimumab 40 mg subcutaneously every other week plus methotrexate (at least 10 mg/week orally or subcutaneously) for 52 weeks. After Week 52 an observational extension period ensued where participants were treated at the discretion of the investigator.

生物：adalimumab

40 mg every other week via subcutaneous injection

其他名称：

• ABT-D2E7
• 修美乐

药品：methotrexate

At least 10 mg/week administered orally or subcutaneously

实验性的：Methotrexate

Participants discontinued adalimumab and continued to receive methotrexate (at least 10 mg/week orally or subcutaneously) for 52 weeks. Participants with a significant increase in RA disease activity were re-instituted to adalimumab 40 mg every other week (rescue arm). After Week 52 an observational extension period ensued where participants were treated at the discretion of the investigator.

药品：methotrexate

At least 10 mg/week administered orally or subcutaneously

Percentage of Participants in Remission at Week 28

Remission is defined as a Disease Activity Score (DAS)28 of less than 2.6. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein (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.

In this analysis participants in the methotrexate treatment group with a DAS28 score ≥ 2.6 (and thus allocated to rescue therapy with adalimumab) prior to Week 28 were considered not to be in remission at Week 28. Also, participants who did not complete 28 weeks were considered not in remission.

Percentage of Participants in Remission at Week 28 in the Full Analysis Set 2 (FAS2)

Remission is defined as a Disease Activity Score (DAS)28 of less than 2.6. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein (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.

In this analysis participants in the methotrexate treatment group with a DAS28 score ≥ 2.6 (and thus allocated to rescue therapy with adalimumab) prior to Week 28 were considered not to be in remission at Week 28. Also, participants who did not complete 28 weeks were considered not in remission.

Percentage of Participants in Remission at Week 52

Remission is defined as a Disease Activity Score (DAS)28 of less than 2.6. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein (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.

In this analysis participants in the methotrexate treatment group with a DAS28 score ≥ 2.6 (and thus allocated to rescue therapy with adalimumab) prior to Week 52 were considered not to be in remission at Week 52. Also, participants who did not complete 52 weeks were considered not in remission.

Percentage of Participants in Remission at Week 52 (FAS2)

Remission is defined as a Disease Activity Score (DAS)28 of less than 2.6. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein (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. Also, participants who did not complete 52 weeks were considered not in remission.

In this analysis participants in the methotrexate treatment group with a DAS28 score ≥ 2.6 (and thus allocated to rescue therapy with adalimumab) prior to Week 52 were considered not to be in remission at Week 52.

Number of Participants With a Flare

Flare is defined as DAS28 ≥2.6 or an increase from Baseline in the DAS28 of greater than 1.2 units. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein (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.

Percentage of Participants With Response to Adalimumab Treatment (Return to Baseline DAS28 + ≤ 10%) After a Flare

For participants with a flare and treated with adalimumab rescue therapy, response was defined as return to Baseline DAS28 + ≤ 10% after reinstitution of adalimumab (rescue therapy).

The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein (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.

Percentage of Participants With Response to Adalimumab Treatment (DAS28 <2.6 or DAS28 Decrease >1.2 Units) After a Flare

For participants with a flare and treated with adalimumab rescue therapy, response was defined as DAS28 less than 2.6 or DAS28 decrease of greater than 1.2 units after reinstitution of adalimumab (rescue therapy). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein (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.

Health Assessment Questionnaire (HAQ) Total Score by Visit

Physical function was evaluated using the Health Assessment Questionnaire - Disability Index (HAQ-DI), a patient-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.

European Quality of Life-5 Dimensions (EQ-5D) Mobility Score by Visit

The EQ-5D is an international, standardized, generic instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their mobility health state:

Level 1: I have no problems in walking about;

Level 2: I have some problems in walking about;

Level 3: I am confined to bed.

European Quality of Life-5 Dimensions (EQ-5D) Self-care Score by Visit

The EQ-5D is an international, standardized, generic instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their self-care health state:

Level 1: I have no problems with self-care;

Level 2: I have some problems washing or dressing myself;

Level 3: I am unable to wash or dress myself.

European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score by Visit

The EQ-5D is an international, standardized, generic instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their health state with regard to usual activities (work, study, housework, family, or leisure activities):

Level 1: I have no problems performing my usual activities;

Level 2: I have some problems performing my usual activities;

Level 3: I am unable to perform my usual activities.

European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score by Visit

The EQ-5D is an international, standardized, generic instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their pain/discomfort health state:

Level 1: I have no pain or discomfort;

Level 2: I have moderate pain or discomfort;

Level 3: I have extreme pain or discomfort.

European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score by Visit

The EQ-5D is an international, standardized, generic instrument for describing and valuing health status. Participants were asked to indicate which of the following statements best describes their anxiety/depression health state:

Level 1: I am not anxious or depressed;

Level 2: I am moderately anxious or depressed;

Level 3: I am extremely anxious or depressed.

European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) by Visit

The EQ-5D is an international, standardized, generic instrument for describing and evaluating health status. Health status is assessed by patients evaluating their health on a vertical, visual analog scale from 0 to 100 where the endpoints are labeled 'Worst imaginable health state' (0) and 'Best imaginable health state' (100).

Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale by Visit

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.

Work Instability Score (WIS) for RA: I'm Getting up Earlier Because of Arthritis

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 1, participants selected either Yes or No if the following statement currently applied to them or not: I'm getting up earlier because of the arthritis.

Work Instability Score (WIS) for RA: I Get Very Stiff at Work

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 2, participants selected either Yes or No if the following statement currently applied to them or not: I get very stiff at work.

Work Instability Score (WIS) for RA: I'm Finding my Job is About All I Can Manage

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 3, participants selected either Yes or No if the following statement currently applied to them or not: I'm finding my job is about all I can manage.

Work Instability Score (WIS) for RA: The Stress of my Job Makes my Arthritis Flare

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 4, participants selected either Yes or No if the following statement currently applied to them or not: The stress of my job makes my arthritis flare.

Work Instability Score (WIS) for RA: I'm Finding Any Pressure on my Hands is a Problem

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 5, participants selected either Yes or No if the following statement currently applied to them or not: I'm finding any pressure on my hands is a problem.

Work Instability Score (WIS) for RA: I Get Good Days and Bad Days at Work

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 6, participants selected either Yes or No if the following statement currently applied to them or not: I get good days and bad days at work.

Work Instability Score (WIS) for RA: I Can Get my Job Done, I'm Just a Lot Slower

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 7, participants selected either Yes or No if the following statement currently applied to them or not: I can get my job done, I'm just a lot slower.

Work Instability Score (WIS) for RA: If I Don't Reduce my Hours I May Have to Give up Work

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 8, participants selected either Yes or No if the following statement currently applied to them or not: If I don't reduce my hours I may have to give up work.

Work Instability Score (WIS) for RA: I am Very Worried About my Ability to Keep Working

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 9, participants selected either Yes or No if the following statement currently applies to them or not: I am very worried about my ability to keep working.

Work Instability Score (WIS) for RA: I Have Pain or Stiffness All the Time at Work

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 10, participants selected either Yes or No if the following statement currently applies to them or not: I have pain or stiffness all the time at work.

Work Instability Score (WIS) for RA: I Don't Have the Stamina to Work Like I Used to

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 11, participants selected either Yes or No if the following statement currently applies to them or not: I don't have the stamina to work like I used to.

Work Instability Score (WIS) for RA: I Have Used my Vacation so That I Don't Have to Take Sick Leave

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 12, participants selected either Yes or No if the following statement currently applies to them or not: I have used my vacation so that I don't have to take sick leave.

Work Instability Score (WIS) for RA: I Push Myself to go to Work Because I Don't Want to Give in to the Arthritis

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 13, participants selected either Yes or No if the following statement currently applies to them or not: I push myself to go to work because I don't want to give in to the arthritis.

Work Instability Score (WIS) for RA: Sometimes I Can't Face Being at Work All Day

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 14, participants selected either Yes or No if the following statement currently applies to them or not: Sometimes I can't face being at work all day.

Work Instability Score (WIS) for RA: I Have to Say No to Certain Things at Work

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 15, participants selected either Yes or No if the following statement currently applies to them or not: I have to say no to certain things at work.

Work Instability Score (WIS) for RA: I've Got to Watch How Much I do Certain Things at Work

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 16, participants selected either Yes or No if the following statement currently applies to them or not: I've got to watch how much I do certain things at work.

Work Instability Score (WIS) for RA: I Have Great Difficulty Opening Some of the Doors at Work

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 17, participants selected either Yes or No if the following statement currently applies to them or not: I have great difficulty opening some of the doors at work.

Work Instability Score (WIS) for RA: I Have to Allow Myself Extra Time to do Some Jobs

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 18, participants selected either Yes or No if the following statement currently applies to them or not: I have to allow myself extra time to do some jobs.

Work Instability Score (WIS) for RA: It's Very Frustrating Because I Can't Always do Things at Work

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 19, participants selected either Yes or No if the following statement currently applies to them or not: It's very frustrating because I can't always do things at work.

Work Instability Score (WIS) for RA: I Feel I May Have to Give up Work

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 20, participants selected either Yes or No if the following statement currently applies to them or not: I feel I may have to give up work.

Work Instability Score (WIS) for RA: I Get on With the Work But Afterwards I Have a Lot of Pain

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 21, participants selected either Yes or No if the following statement currently applies to them or not: I get on with the work but afterwards I have a lot of pain.

Work Instability Score (WIS) for RA: When I'm Feeling Tired All the Time Work is a Grind

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 22, participants selected either Yes or No if the following statement currently applies to them or not: When I'm feeling tired all the time work is a grind.

Work Instability Score (WIS) for RA: I'd Like Another Job But I am Restricted to What I Can do

Work Instability (defined as the mismatch between the person's abilities and the demands of work) Score is a 23-item questionnaire designed to indicate the participant's level of risk for work disability. In question 23, participants selected either Yes or No if the following statement currently applied to them or not: I'd like another job but I am restricted to what I can do.

Work Productivity and Activity Impairment (WPAI): Currently Employed

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess work and activity impairment due to symptoms of rheumatoid arthritis in the last 7 days. The self-administered questionnaire consists of 6 questions. Question 1 asks participants to indicate if they are currently employed or working for pay (Yes or No).

Work Productivity and Activity Impairment (WPAI): Hours Missed From Work

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess work and activity impairment due to symptoms of rheumatoid arthritis in the last 7 days. The self-administered questionnaire consists of 6 questions. Question 2 asks participants who are employed or working for pay to indicate the number of hours missed from work due to problems associated with their rheumatoid arthritis.

Work Productivity and Activity Impairment (WPAI): Hours Missed From Work for Other Reasons

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess work and activity impairment due to symptoms of rheumatoid arthritis in the last 7 days. The self-administered questionnaire consists of 6 questions. Question 3 asks participants who are employed or working for pay to indicate the number of hours missed from work due to reasons other than rheumatoid arthritis.

Work Productivity and Activity Impairment (WPAI): Hours Worked

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess work and activity impairment due to symptoms of rheumatoid arthritis in the last 7 days. The self-administered questionnaire consists of 6 questions. Question 4 asks participants who are employed or working for pay to indicate the number of hours actually worked during the past 7 days.

Work Productivity and Activity Impairment (WPAI): Work Productivity

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess work and activity impairment due to symptoms of rheumatoid arthritis in the last 7 days. The self-administered questionnaire consists of 6 questions. Question 5 asks participants who are employed or working for pay to indicate how much their rheumatoid arthritis impaired their productivity while working in the past 7 days on a scale from 0 (no effect) to 10 (completely prevented from working).

Work Productivity and Activity Impairment (WPAI): Daily Activities

The Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire was used to assess work and activity impairment due to symptoms of rheumatoid arthritis in the last 7 days. The self-administered questionnaire consists of 6 questions. Question 6 asks participants to indicate how much their rheumatoid arthritis affected their ability to do their regular daily activities such as housework, childcare, exercising, shopping, studying, etc, in the past 7 days on a scale from 0 (no effect) to 10 (completely prevented from doing daily activities).

Change From Baseline in Radiological Modified Total Sharp Score

The van der Heijde modified Total Sharp Score (mTSS) is a measure of the level of joint damage. X-rays of hands and feet were taken at Baseline, Week 52 and the Week 104-156 visit. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 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.