Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study
Huizinga TWJ, Conaghan PG, Martin-Mola E, Schett G, Amital H, Xavier RM, Troum O, Aassi M, Bernasconi C, Dougados M (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 74
Pages Range: 35-43
Journal Issue: 1
DOI: 10.1136/annrheumdis-2014-205752
Abstract
To assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission.ACT-RAY was a double-blind 3-year trial. Patients with active rheumatoid arthritis despite MTX were randomised to add TCZ to ongoing MTX (add-on strategy) or switch to TCZ plus PBO (switch strategy). Using a treat-to-target approach, open-label conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), other than MTX, were added from week 24 if Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) >3.2. Between weeks 52 and 104, patients in sustained clinical remission (DAS28-ESR <2.6 at two consecutive visits 12 weeks apart) discontinued TCZ and were assessed every 4 weeks for 1 year. If sustained remission was maintained, added csDMARDs, then MTX/PBO, were discontinued.Of the 556 randomised patients, 76% completed year 2. Of patients entering year 2, 50.4% discontinued TCZ after achieving sustained remission and 5.9% achieved drug-free remission. Most patients who discontinued TCZ (84.0%) had a subsequent flare, but responded well to TCZ reintroduction. Despite many patients temporarily stopping TCZ, radiographic progression was minimal, with differences favouring add-on treatment. Rates of serious adverse events and serious infections per 100 patient-years were 12.2 and 4.4 in add-on and 15.0 and 3.7 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3×upper limit of normal were more frequent in add-on (14.3%) versus switch patients (5.4%).Treat-to-target strategies could be successfully implemented with TCZ to achieve sustained remission, after which TCZ was stopped. Biologic-free remission was maintained for about 3 months, but most patients eventually flared. TCZ restart led to rapid improvement.NCT00810199.
Authors with CRIS profile
Involved external institutions
University of Paris 5 - René Descartes / Université Paris V René Descartes
France (FR)
F. Hoffmann-La Roche Ltd
Switzerland (CH)
University of Southern California (USC)
United States (USA) (US)
Hospital de Clínicas de Porto Alegre (HCPA)
Brazil (BR)
Chaim Sheba Medical Center at Tel HaShomer / המרכז הרפואי עש חיים שיבא – תל השומר
Israel (IL)
Hospital Universitario La Paz
Spain (ES)
University of Leeds
United Kingdom (GB)
Leiden University
Netherlands (NL)
France (FR)
F. Hoffmann-La Roche Ltd
Switzerland (CH)
University of Southern California (USC)
United States (USA) (US)
Hospital de Clínicas de Porto Alegre (HCPA)
Brazil (BR)
Chaim Sheba Medical Center at Tel HaShomer / המרכז הרפואי עש חיים שיבא – תל השומר
Israel (IL)
Hospital Universitario La Paz
Spain (ES)
University of Leeds
United Kingdom (GB)
Leiden University
Netherlands (NL)
How to cite
APA:
Huizinga, T.W.J., Conaghan, P.G., Martin-Mola, E., Schett, G., Amital, H., Xavier, R.M.,... Dougados, M. (2015). Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study. Annals of the Rheumatic Diseases, 74(1), 35-43. https://doi.org/10.1136/annrheumdis-2014-205752
MLA:
Huizinga, T. W. J., et al. "Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study." Annals of the Rheumatic Diseases 74.1 (2015): 35-43.
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