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.
RCT Entities:
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: Roy Fleischmann; Michael E Weinblatt; Michael Schiff; Dinesh Khanna; Michael A Maldonado; Anagha Nadkarni; Daniel E Furst Journal: Arthritis Care Res (Hoboken) Date: 2016-07 Impact factor: 4.794
Authors: Dimitrios A Pappas; Joel M Kremer; Jenny Griffith; George Reed; Bob Salim; Chitra Karki; Vishvas Garg Journal: Rheumatol Ther Date: 2017-08-24
Authors: Josef S Smolen; Joel M Kremer; Carol L Gaich; Amy M DeLozier; Douglas E Schlichting; Li Xie; Ivaylo Stoykov; Terence Rooney; Paul Bird; Juan Miguel Sánchez Bursón; Mark C Genovese; Bernard Combe Journal: Ann Rheum Dis Date: 2016-10-31 Impact factor: 19.103
Authors: Gerd R Burmester; Robert Landewé; Mark C Genovese; Alan W Friedman; Nathan D Pfeifer; Nupun A Varothai; Ana P Lacerda Journal: Ann Rheum Dis Date: 2016-06-23 Impact factor: 19.103
Authors: Vibeke Strand; Eduardo Mysler; Robert J Moots; Gene V Wallenstein; Ryan DeMasi; David Gruben; Koshika Soma; Noriko Iikuni; Josef S Smolen; Roy Fleischmann Journal: RMD Open Date: 2019-10-01
Authors: Stanley B Cohen; Yoshiya Tanaka; Xavier Mariette; Jeffrey R Curtis; Eun Bong Lee; Peter Nash; Kevin L Winthrop; Christina Charles-Schoeman; Lisy Wang; Connie Chen; Kenneth Kwok; Pinaki Biswas; Andrea Shapiro; Ann Madsen; Jürgen Wollenhaupt Journal: RMD Open Date: 2020-10