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.

Patient‐Reported Outcomes From a Two‐Year Head‐to‐Head Comparison of Subcutaneous Abatacept and Adalimumab for Rheumatoid Arthritis

“…The results presented here are also consistent with published PRO data for adalimumab 27, 28, 29. In the Anti‐TNF Research Study Program of the Monoclonal Antibody Adalimumab trial, patients who had an inadequate response to MTX and were treated with adalimumab plus MTX demonstrated significant improvements in physical function from baseline to year 4 (mean Health Assessment Questionnaire disability index [HAQ DI] 0.7 and 1.5, respectively [ P < 0.001]) 27.…”

“…In the Anti‐TNF Research Study Program of the Monoclonal Antibody Adalimumab trial, patients who had an inadequate response to MTX and were treated with adalimumab plus MTX demonstrated significant improvements in physical function from baseline to year 4 (mean Health Assessment Questionnaire disability index [HAQ DI] 0.7 and 1.5, respectively [ P < 0.001]) 27. Similarly, in the DE019 adalimumab study, patients who had an inadequate response to MTX who received up to 10 years of adalimumab plus MTX therapy demonstrated a reduction in mean HAQ DI from 1.4 at baseline to 0.7 at year 10, while 42% of patients achieved HAQ DI <0.5 (normal functionality) at year 10 28. In the PREMIER study, significant improvements from baseline to year 2 in HAQ DI ( P < 0.0001), Short Form 36 health survey physical component summary score ( P < 0.0001), patient global assessment score ( P < 0.0001), and pain score ( P < 0.0001) were reported by patients with early RA treated with adalimumab plus MTX versus patients treated with MTX monotherapy 29.…”

The biochemical, histopathological and clinical comparison of the neuroprotective effects of subcutaneous adalimumab and intravenous methylprednisolone in an experimental compressive spinal cord trauma model

“…It is used successfully at a dose of 40 mg/kg subcutaneously every 2 weeks in the treatment of disorders such as Crohn's disease, ulcerative colitis, psoriasis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (13,14,42,43,59,65).…”

Does Combined Clinical and Ultrasound Assessment Allow Selection of Individuals With Rheumatoid Arthritis for Sustained Reduction of Anti–Tumor Necrosis Factor Therapy?

“…In the treatment of rheumatoid arthritis (RA), biologic therapies, including anti-tumor necrosis factor (anti-TNF) inhibitors, reduce disease activity (1)(2)(3), preserve physical function, and prevent joint damage and consequent disability (4)(5)(6)(7). Current guidelines for the management of RA propose rapid escalation of drug treatment to control 1 disease activity (8,9).…”