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

NCT ID: NCT00808509

Last Updated: 2013-12-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2012-09-30

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.

Conditions

Arthritis, Rheumatoid

Keywords

adalimumab,Remission,drug discontinuation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

adalimumab

Intervention Type: BIOLOGICAL

40 mg every other week via subcutaneous injection

methotrexate

Intervention Type: DRUG

At least 10 mg/week administered orally or subcutaneously

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.

Group Type: EXPERIMENTAL

methotrexate

Intervention Type: DRUG

At least 10 mg/week administered orally or subcutaneously

Interventions

adalimumab

40 mg every other week via subcutaneous injection

Intervention Type: BIOLOGICAL

methotrexate

At least 10 mg/week administered orally or subcutaneously

Intervention Type: DRUG

Other Intervention Names

ABT-D2E7; HUMIRA

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharma Consulting Group AB

INDUSTRY

Sponsor Role: collaborator

AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mikael Heimburger, MD

Role: STUDY_DIRECTOR

AbbVie AB

Locations

Site Reference ID/Investigator# 22062

Linköping, , Sweden

Site Reference ID/Investigator# 14022

Lund, , Sweden

Site Reference ID/Investigator# 14023

Malmo, , Sweden

Site Reference ID/Investigator# 14301

Oskarström, , Sweden

Site Reference ID/Investigator# 20241

Skövde, , Sweden

Site Reference ID/Investigator# 4918

Stockholm, , Sweden

Site Reference ID/Investigator# 14021

Stockholm, , Sweden

Site Reference ID/Investigator# 14302

Uppsala, , Sweden

Countries

Sweden

References

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.

Reference Type: DERIVED

PMID: 26819752 (View on PubMed)

Related Links

http://rxabbvie.com

Related Info

Other Identifiers

2008-004398-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

W10-046

Identifier Type: -

Identifier Source: org_study_id