Arthritis, RheumatoidPhase 4ADMIRENCT00808509
A Pilot Study of the Feasibility of Discontinuation of Adalimumab in Stable Rheumatoid Arthritis Patients in Clinical Remission
A Phase 4 study testing adalimumab and methotrexate in people with Arthritis, Rheumatoid, run by AbbVie (prior sponsor, Abbott) at 8 sites in Sweden.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthritis, Rheumatoid
- What is being tested?
- adalimumab and methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 8 sitesSweden
- Study dates
- Jan 2009to Sep 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Sweden8 sites
Site Reference ID/Investigator# 22062
Linköping, 581 85
Site Reference ID/Investigator# 14022
Lund, 22185
Site Reference ID/Investigator# 14023
Malmö, 20502
Site Reference ID/Investigator# 14301
Oskarström, 31392
Site Reference ID/Investigator# 20241
Skövde, 54185
Site Reference ID/Investigator# 4918
Stockholm, 171 76
Site Reference ID/Investigator# 14021
Stockholm, SE-141 86
Site Reference ID/Investigator# 14302
Uppsala, 75185
About this study
Official title: A Pilot Study of the Feasibility of Discontinuation of Adalimumab in Stable Rheumatoid Arthritis Patients in Clinical Remission (ADMIRE)
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.
Read the 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.
- Conditions
- Arthritis, Rheumatoid
- Being tested
- adalimumab, methotrexate
- Keywords
- adalimumab,Remission,drug discontinuation
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
adalimumabBiological
Also called ABT-D2E7, HUMIRA
40 mg every other week via subcutaneous injection
methotrexateDrug
At least 10 mg/week administered orally or subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| Adalimumab + MTX | Active comparator | 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. Receives: Biological: adalimumab; Drug: methotrexate |
| Methotrexate | Experimental | 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. Receives: Drug: methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 28
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.
Measured: Week 28
Secondary outcomes (43)
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.
Measured: Week 52
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.
Measured: 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.
Measured: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, and 52
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.
Measured: 1 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, and 13 to 16 weeks after reinstitution of adalimumab rescue therapy
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.
Measured: 1 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, and 13 to 16 weeks after reinstitution of adalimumab rescue therapy
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.
Measured: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
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.
Measured: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
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.
Measured: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
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.
Measured: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
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.
Measured: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
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.
Measured: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
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).
Measured: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
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.
Measured: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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).
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline and at Weeks 12, 28, 52 and 104-156
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).
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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).
Measured: Baseline and at Weeks 12, 28, 52, and 104-156
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.
Measured: Baseline, Week 52, and Weeks 104-156
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2008 (estimated)
- Study startJan 2009
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie (prior sponsor, Abbott)
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pharma Consulting Group AB
- Responsible party
- Sponsor
- Investigators
- Mikael Heimburger, MD, Study director, AbbVie AB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00808509
- Sponsor's protocol ID
- W10-046
- Other IDs
- 2008-004398-16, 2008
- Acronym
- ADMIRE
- Status last verified
- Nov 2013
- First submitted
- 12 Dec 2008
- Last updated
- 16 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Chatzidionysiou K, Turesson C, Teleman A, Knight A, Lindqvist E, Larsson P, Coster L, Forslind K, van Vollenhoven R, Heimburger M. A multicentre, randomised, controlled, open-label pilot study on the feasibility of discontinuation of adalimumab in established patients with rheumatoid arthritis in stable clinical remission. RMD Open. 2016 Jan 14;2(1):e000133. doi: 10.1136/rmdopen-2015-000133. eCollection 2016.
PubMed 26819752
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of the Feasibility of Discontinuation of Adalimumab in Stable Rheumatoid Arthritis Patients in Clinical Remission (ADMIRE)
- ClinicalTrials.gov ID
- NCT00808509
- Acronym / sponsor ID
- ADMIRE / W10-046
- Conditions
- Arthritis, Rheumatoid
- Keywords
- adalimumab,Remission,drug discontinuation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- AbbVie (prior sponsor, Abbott)Industry (pharma, biotech, devices)
- Collaborators
- Pharma Consulting Group AB
- Study start
- Jan 2009
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 16 Dec 2008 (estimated)
- Results
- Posted 20 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adalimumab + MTX | Active comparator | Biological: adalimumab, Drug: methotrexateParticipants 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. |
| Methotrexate | Experimental | Drug: methotrexateParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| adalimumabAlso: ABT-D2E7, HUMIRA40 mg every other week via subcutaneous injection | Biological | Adalimumab + MTX |
| methotrexateAt least 10 mg/week administered orally or subcutaneously | Drug | Adalimumab + MTX, Methotrexate |
Primary outcome
Percentage of Participants in Remission at Week 28
Time frame: 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)
Time frame: 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.
43 secondary outcomes
Percentage of Participants in Remission at Week 52
Time frame: Week 52
Percentage of Participants in Remission at Week 52 (FAS2)
Time frame: Week 52
Number of Participants With a Flare
Time frame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, and 52
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
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
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)
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)
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)
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)
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)
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)
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)
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)
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
Work Instability Score (WIS) for RA: I Get Very Stiff at Work
Time frame: Baseline and at Weeks 12, 28, 52, and 104-156
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Work Productivity and Activity Impairment (WPAI): Currently Employed
Time frame: Baseline and at Weeks 12, 28, 52, and 104-156
Work Productivity and Activity Impairment (WPAI): Hours Missed From Work
Time frame: Baseline and at Weeks 12, 28, 52, and 104-156
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
Work Productivity and Activity Impairment (WPAI): Hours Worked
Time frame: Baseline and at Weeks 12, 28, 52 and 104-156
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26819752Chatzidionysiou K, Turesson C, Teleman A, Knight A, Lindqvist E, Larsson P, Coster L, Forslind K, van Vollenhoven R, Heimburger M. A multicentre, randomised, controlled, open-label pilot study on the feasibility of discontinuation of adalimumab in established patients with rheumatoid arthritis in stable clinical remission. RMD Open. 2016 Jan 14;2(1):e000133. doi: 10.1136/rmdopen-2015-000133. eCollection 2016.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mikael Heimburger, MD study director
AbbVie AB
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing adalimumab and methotrexate in people with Arthritis, Rheumatoid, run by AbbVie (prior sponsor, Abbott) at 8 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants in Remission at Week 28 (time frame: Week 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00808509, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2013.