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

This study has been completed.
Sponsor:
Collaborator:
Pharma Consulting Group AB
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT00808509
First received: December 12, 2008
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

The purpose of this pilot study is to investigate the possibility of discontinuing adalimumab therapy in patients with rheumatoid arthritis who are in stable remission after treatment with adalimumab in combination with methotrexate.


Condition Intervention Phase
Arthritis, Rheumatoid
Biological: adalimumab
Drug: methotrexate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Pilot Study of the Feasibility of Discontinuation of Adalimumab in Stable Rheumatoid Arthritis Patients in Clinical Remission (ADMIRE)

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Percentage of Participants in Remission at Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Week 28 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Percentage of Participants in Remission at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, and 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, and 13 to 16 weeks after reinstitution of adalimumab rescue therapy ] [ Designated as safety issue: No ]

    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 [ Time Frame: 1 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, and 13 to 16 weeks after reinstitution of adalimumab rescue therapy ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52 and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and at Weeks 12, 28, 52, and 104-156 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 52, and Weeks 104-156 ] [ Designated as safety issue: No ]
    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.


Enrollment: 33
Study Start Date: January 2009
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Biological: adalimumab
40 mg every other week via subcutaneous injection
Other Names:
  • ABT-D2E7
  • HUMIRA
Drug: methotrexate
At least 10 mg/week administered orally or subcutaneously
Experimental: 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.
Drug: methotrexate
At least 10 mg/week administered orally or subcutaneously

Detailed Description:

Treatments with adalimumab and other tumor necrosis factor (TNF) blockers, once started as therapy for rheumatoid arthritis (RA), are usually continued indefinitely. Information concerning the possibility of discontinuing anti-TNF therapy in RA patients who are in remission is limited. This is a pilot study in one country to study the effect of adalimumab discontinuation. The objective is to assess the proportion of patients with established RA in stable remission (Disease Activity Score [DAS]28 <2.6) after treatment with adalimumab in combination with methotrexate, in whom it is possible to discontinue adalimumab and to compare the remission rates among patients on sustained therapy with adalimumab + methotrexate with remission rates among patients who discontinued adalimumab.

Rheumatoid arthritis patients in stable remission (DAS28 < 2.6) treated with adalimumab + methotrexate were randomized in a 1:1 ratio to continue with adalimumab treatment or discontinue adalimumab treatment for the following 52 weeks. Subsequently an observational extension was conducted to observe patients treated at the discretion of the investigator. The observational extension period lasted until Weeks 105 - 156 (average Week 125) and consisted of one follow-up visit. Participants randomized to discontinue adalimumab therapy will be reinstituted to adalimumab if DAS28-score increases by >1.2 units from baseline and/or is scored ≥2.6 at any visit during the study and will be followed for an additional 12 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years.
  • Diagnosis of RA as defined by the 1987-revised American College of Rheumatology (ACR)-classification and has positive rheumatoid factor (RF) test or erosion on X-ray of hands or feet.
  • Currently treated with adalimumab and MTX (at least 10 mg/week; orally or subcutaneously).
  • In remission as defined by disease activity score (DAS)28 <2.6 for at least the past 3 months.
  • Concomitant disease-modifying anti-rheumatic drug (DMARD) or oral corticosteroid therapy has been stable for at least 3 months at study entry.
  • Female subject is either not of childbearing potential or is practicing a relevant method of birth control.
  • Subject is judged to be in good general health.
  • Subjects must be able and willing to provide written informed consent.
  • Subjects must be able and willing to self-administer subcutaneous (SC) injections or have a qualified person available to administer SC injections.

Exclusion Criteria:

  • Treatment with intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks.
  • Oral prednisone or prednisone equivalent > 10 mg/day at baseline.
  • Joint surgery within the preceding two months.
  • History of acute inflammatory joint disease other than RA.
  • Treatment with any investigational drug within 30 days or 5 half lives, whichever is longer prior to study entry.
  • Poorly controlled medical condition, which would put the subject at risk by participation in the study.
  • History of clinically significant hematologic, renal or liver disease.
  • Diagnosis of, or history suggestive of, central nervous system (CNS) demyelinating disease.
  • History of cancer or lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma of the cervix.
  • History of listeriosis, histoplasmosis, untreated tuberculosis (TB), persistent chronic infections, or recent active infections.
  • Known immune deficiency or human immunodeficiency virus (HIV).
  • Female who is pregnant or breast-feeding or considering becoming pregnant or breast feeding during the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00808509

Locations
Sweden
Site Reference ID/Investigator# 22062
Linkoping, Sweden, 581 85
Site Reference ID/Investigator# 14022
Lund, Sweden, 22185
Site Reference ID/Investigator# 14023
Malmo, Sweden, 20502
Site Reference ID/Investigator# 14301
Oskarstroem, Sweden, 31392
Site Reference ID/Investigator# 20241
Skoevde, Sweden, 54185
Site Reference ID/Investigator# 14021
Stockholm, Sweden, SE-141 86
Site Reference ID/Investigator# 4918
Stockholm, Sweden, 171 76
Site Reference ID/Investigator# 14302
Uppsala, Sweden, 75185
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Pharma Consulting Group AB
Investigators
Study Director: Mikael Heimburger, MD AbbVie AB
  More Information

Additional Information:
No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT00808509     History of Changes
Other Study ID Numbers: W10-046, 2008-004398-16
Study First Received: December 12, 2008
Results First Received: September 19, 2013
Last Updated: November 21, 2013
Health Authority: Sweden: Medical Products Agency

Keywords provided by AbbVie:
adalimumab,Remission,drug discontinuation

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Adalimumab
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Inflammatory Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014