Clinical, functional, and radiographic benefits of longterm adalimumab plus methotrexate: final 10-year data in longstanding rheumatoid arthritis.

Abstract

OBJECTIVE:

To examine the longterm effectiveness and safety of adalimumab in patients with longstanding rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX), and to assess the effect of a 1-year delay in initiation of combination therapy.

METHODS:

DE019 was a 1-year randomized controlled trial (RCT) in which patients received adalimumab 20 mg weekly, adalimumab 40 mg every other week (eow), or placebo; all received concomitant MTX. Patients completing the RCT could receive open-label adalimumab 40 mg eow + MTX for an additional 9 years. Clinical, functional, and radiographic outcomes were assessed using composite measures of disease activity (e.g., American College of Rheumatology responses, 28-joint Disease Activity Score with C-reactive protein, Simplified Disease Activity Index), Health Assessment Questionnaire-Disability Index, and the modified total Sharp score (mTSS), respectively.

RESULTS:

Of the 619 patients randomized, 457 entered the open-label extension; 202 completed 10 years. At Year 10, patients demonstrated effective disease control and inhibition of radiographic progression. Differences in clinical and functional responses between adalimumab + MTX and placebo + MTX observed during the RCT became less apparent at Year 10. Still, patients who initially received adalimumab + MTX had significantly lower mean ΔmTSS at Year 10 compared with patients who initially received placebo + MTX. No new safety signals arose following up to 10 years of adalimumab + MTX exposure.

CONCLUSION:

During up to 10 years of treatment with adalimumab + MTX, patients with longstanding RA experienced effective disease control with no change to the expected safety profile. A 1-year delay in receipt of adalimumab + MTX was associated with reduced effectiveness, suggesting that a window of opportunity to prevent irreversible damage exists even in a population with established RA.

• Authors: Edward C Keystone, Désirée van der Heijde, Arthur Kavanaugh, Hartmut Kupper, Shufang Liu, Benoît Guérette, Neelufar Mozaffarian
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 40 Issue 9 Pg. 1487-97 (Sep 2013) ISSN: 0315-162X [Print] Canada
• PMID: 23818718 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Adalimumab
• Methotrexate

Topics

• Adalimumab
• Adult
• Aged
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Antirheumatic Agents (adverse effects, therapeutic use)
• Arthritis, Rheumatoid (diagnostic imaging, drug therapy, physiopathology)
• Disease Progression
• Drug Therapy, Combination
• Female
• Humans
• Longitudinal Studies
• Male
• Methotrexate (adverse effects, therapeutic use)
• Middle Aged
• Radiography
• Severity of Illness Index
• Treatment Outcome