Clinical trial NCT00808509: A Pilot Study of the Feasibility of Discontinuation of Adalimumab in Stable Rheumatoid Arthritis Patients in Clinical Remission
Official title: A Pilot Study of the Feasibility of Discontinuation of Adalimumab in Stable Rheumatoid Arthritis Patients in Clinical Remission (ADMIRE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Arthritis, Rheumatoid
Keywords: adalimumab,Remission,drug discontinuation
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Pharma Consulting Group AB
First posted: 2008-12-16
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief 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.

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 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.

Primary outcomes:
measure: Percentage of Participants in Remission at Week 28
timeFrame: Week 28
measure: Percentage of Participants in Remission at Week 28 in the Full Analysis Set 2 (FAS2)
timeFrame: Week 28
Secondary outcomes:
measure: Percentage of Participants in Remission at Week 52
timeFrame: Week 52
measure: Percentage of Participants in Remission at Week 52 (FAS2)
timeFrame: Week 52
measure: Number of Participants With a Flare
timeFrame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, and 52
measure: Percentage of Participants With Response to Adalimumab Treatment (Return to Baseline DAS28 + ≤ 10%) After a Flare
timeFrame: 1 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, and 13 to 16 weeks after reinstitution of adalimumab rescue therapy
measure: Percentage of Participants With Response to Adalimumab Treatment (DAS28 <2.6 or DAS28 Decrease >1.2 Units) After a Flare
timeFrame: 1 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, and 13 to 16 weeks after reinstitution of adalimumab rescue therapy
measure: Health Assessment Questionnaire (HAQ) Total Score by Visit
timeFrame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
measure: European Quality of Life-5 Dimensions (EQ-5D) Mobility Score by Visit
timeFrame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
measure: European Quality of Life-5 Dimensions (EQ-5D) Self-care Score by Visit
timeFrame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
measure: European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score by Visit
timeFrame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
measure: European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score by Visit
timeFrame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
measure: European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score by Visit
timeFrame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
measure: European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) by Visit
timeFrame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
measure: Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale by Visit
timeFrame: Baseline and Weeks 4, 8, 12, 20, 28, 36, 44, 52, and 104-156 (extension period visit)
measure: Work Instability Score (WIS) for RA: I'm Getting up Earlier Because of Arthritis
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Get Very Stiff at Work
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I'm Finding my Job is About All I Can Manage
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: The Stress of my Job Makes my Arthritis Flare
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I'm Finding Any Pressure on my Hands is a Problem
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Get Good Days and Bad Days at Work
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Can Get my Job Done, I'm Just a Lot Slower
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: If I Don't Reduce my Hours I May Have to Give up Work
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I am Very Worried About my Ability to Keep Working
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Have Pain or Stiffness All the Time at Work
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Don't Have the Stamina to Work Like I Used to
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Have Used my Vacation so That I Don't Have to Take Sick Leave
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Push Myself to go to Work Because I Don't Want to Give in to the Arthritis
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: Sometimes I Can't Face Being at Work All Day
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Have to Say No to Certain Things at Work
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I've Got to Watch How Much I do Certain Things at Work
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Have Great Difficulty Opening Some of the Doors at Work
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Have to Allow Myself Extra Time to do Some Jobs
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: It's Very Frustrating Because I Can't Always do Things at Work
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Feel I May Have to Give up Work
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I Get on With the Work But Afterwards I Have a Lot of Pain
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: When I'm Feeling Tired All the Time Work is a Grind
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Instability Score (WIS) for RA: I'd Like Another Job But I am Restricted to What I Can do
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Productivity and Activity Impairment (WPAI): Currently Employed
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Productivity and Activity Impairment (WPAI): Hours Missed From Work
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Productivity and Activity Impairment (WPAI): Hours Missed From Work for Other Reasons
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Productivity and Activity Impairment (WPAI): Hours Worked
timeFrame: Baseline and at Weeks 12, 28, 52 and 104-156
measure: Work Productivity and Activity Impairment (WPAI): Work Productivity
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Work Productivity and Activity Impairment (WPAI): Daily Activities
timeFrame: Baseline and at Weeks 12, 28, 52, and 104-156
measure: Change From Baseline in Radiological Modified Total Sharp Score
timeFrame: Baseline, Week 52, and Weeks 104-156
Other outcomes:
Locations:
city: Linkoping
country: Sweden
facility: Site Reference ID/Investigator# 22062
city: Lund
country: Sweden
facility: Site Reference ID/Investigator# 14022
city: Malmo
country: Sweden
facility: Site Reference ID/Investigator# 14023
city: Oskarstroem
country: Sweden
facility: Site Reference ID/Investigator# 14301
city: Skoevde
country: Sweden
facility: Site Reference ID/Investigator# 20241
city: Stockholm
country: Sweden
facility: Site Reference ID/Investigator# 4918
city: Stockholm
country: Sweden
facility: Site Reference ID/Investigator# 14021
city: Uppsala
country: Sweden
facility: Site Reference ID/Investigator# 14302
Study officials:
affiliation: AbbVie AB
name: Mikael Heimburger, MD
role: STUDY_DIRECTOR
References:
citation: 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.