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
- T W J Huizinga1,
- Philip G Conaghan2,
- Emilio Martin-Mola3,
- Georg Schett4,
- Howard Amital5,
- Ricardo M Xavier6,
- Orrin Troum7,
- Maher Aassi8,
- Corrado Bernasconi8,
- Maxime Dougados9
- 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
- 2NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
- 3Department of Rheumatology, Hospital Universitario La Paz, Madrid, Spain
- 4Department of Rheumatology, University of Erlangen-Nuremberg, Erlangen, Germany
- 5Department of Medicine ‘B’, Sheba Medical Center, Tel Hashomer, Israel
- 6Division of Rheumatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- 7Division of Rheumatology, University of Southern California Keck School of Medicine, Santa Monica, California, USA
- 8F.Hoffmann-La Roche Ltd, Basel, Switzerland
- 9Rheumatology B Department, Paris-Descartes University, Cochin Hospital, Paris, France
- Correspondence to Professor T W J Huizinga, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands;
- Received 15 April 2014
- Revised 21 July 2014
- Accepted 10 August 2014
- Published Online First 28 August 2014
Objective 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.
Methods 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.
Results 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%).
Conclusions 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.
Trial registration number NCT00810199.
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