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Extended report
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
  1. T W J Huizinga1,
  2. Philip G Conaghan2,
  3. Emilio Martin-Mola3,
  4. Georg Schett4,
  5. Howard Amital5,
  6. Ricardo M Xavier6,
  7. Orrin Troum7,
  8. Maher Aassi8,
  9. Corrado Bernasconi8,
  10. Maxime Dougados9
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
  3. 3Department of Rheumatology, Hospital Universitario La Paz, Madrid, Spain
  4. 4Department of Rheumatology, University of Erlangen-Nuremberg, Erlangen, Germany
  5. 5Department of Medicine ‘B’, Sheba Medical Center, Tel Hashomer, Israel
  6. 6Division of Rheumatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
  7. 7Division of Rheumatology, University of Southern California Keck School of Medicine, Santa Monica, California, USA
  8. 8F.Hoffmann-La Roche Ltd, Basel, Switzerland
  9. 9Rheumatology B Department, Paris-Descartes University, Cochin Hospital, Paris, France
  1. Correspondence to Professor T W J Huizinga, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands; t.w.j.huizinga{at}lumc.nl

Abstract

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.

  • Rheumatoid Arthritis
  • DMARDs (biologic)
  • Methotrexate

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