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

NCT00808509 | Completed Phase 4 Results

• 2 other identifiers: W10-0462008-004398-16
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 8

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.

Conditions

Arthritis, Rheumatoid

Keywords

adalimumab,Remission,drug discontinuation

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Week 28

Secondary Outcomes (43)

• Percentage of Participants in Remission at Week 52

  Week 52

• Percentage of Participants in Remission at Week 52 (FAS2)

  Week 52

• Number of Participants With a Flare

  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

  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

  1 to 4 weeks, 5 to 8 weeks, 9 to 12 weeks, and 13 to 16 weeks after reinstitution of adalimumab rescue therapy

Study Arms (2)

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.

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.

Drug: methotrexate

Interventions

adalimumab BIOLOGICAL

40 mg every other week via subcutaneous injection

Also known as: ABT-D2E7, HUMIRA

Adalimumab + MTX

methotrexate DRUG

At least 10 mg/week administered orally or subcutaneously

Adalimumab + MTX; Methotrexate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead
• Pharma Consulting Group AB: collaborator

Study Sites (8)

Site Reference ID/Investigator# 22062

Linköping, 581 85, Sweden

Location

Site Reference ID/Investigator# 14022

Lund, 22185, Sweden

Location

Site Reference ID/Investigator# 14023

Malmo, 20502, Sweden

Location

Site Reference ID/Investigator# 14301

Oskarström, 31392, Sweden

Location

Site Reference ID/Investigator# 20241

Skövde, 54185, Sweden

Location

Site Reference ID/Investigator# 4918

Stockholm, 171 76, Sweden

Location

Site Reference ID/Investigator# 14021

Stockholm, SE-141 86, Sweden

Location

Site Reference ID/Investigator# 14302

Uppsala, 75185, Sweden

Location

Related Publications (1)

• 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.

  PMID: 26819752 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Adalimumab; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

800-633-9110

Study Officials

• Mikael Heimburger, MD

  AbbVie AB

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2008
• First Posted: December 16, 2008
• Study Start: January 1, 2009
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: December 16, 2013
• Results First Posted: November 20, 2013

Record last verified: 2013-11

Locations

SE (8)