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SAT0255 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. Huizinga1,
  2. P.G. Conaghan2,
  3. E. Martin-Mola3,
  4. G. Schett4,
  5. H. Amital5,
  6. R.M. Xavier6,
  7. O. Troum7,
  8. M. Aassi8,
  9. C. Bernasconi8,
  10. M. Dougados9
  1. 1Leiden University Medical Center, Leiden, Netherlands
  2. 2University of Leeds, Leeds, United Kingdom
  3. 3Hospital Universitatio La Paz, Madrid, Spain
  4. 4University of Erlangen-Nuremberg, Erlangen, Germany
  5. 5Sheba Medical Center, Tel Hashomer, Israel
  6. 6Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
  7. 7University of Southern California School of Medicine, Santa Monica, United States
  8. 8F. Hoffman-La Roche Ltd., Basel, Switzerland
  9. 9Paris-Descartes University, Cochin Hospital, Paris, France


Background In ACT-RAY, MTX-IR patients (pts) with moderate to severe RA were randomized to either an add-on (tocilizumab [TCZ]+MTX) or a switch (TCZ+placebo [PBO]) strategy. Data at 24 and 52 weeks demonstrated clinical and radiographic benefit without clinically meaningful differences between the 2 arms for most endpoints.1,2 During years 2 and 3, the protocol included a step-down strategy with the goal of achieving drug-free remission (discontinuation of study drugs while DAS28 remained <2.6).

Objectives To compare the safety and efficacy of TCZ-based treatment strategies, to evaluate the treat-to-target (T2T) approach and to assess the course of disease activity in pts who discontinued TCZ due to sustained remission.

Methods ACT-RAY was a phase 3b trial. Pts on stable doses of MTX were randomized to either add TCZ 8 mg/kg IV every 4 weeks or switch to TCZ 8 mg/kg IV with oral PBO. Using a T2T approach, DMARDs other than MTX were added from Week 24 if DAS28>3.2, while maintaining MTX/PBO blinding. Between Weeks 52-104, pts in sustained clinical remission (DAS28<2.6 at 2 consecutive visits 12 weeks apart) discontinued TCZ and were followed up every 4 weeks for 1 year. If sustained remission was maintained, added DMARDs and then MTX/PBO were discontinued. In case of flare, defined at the investigator's discretion, the last effective treatment or TCZ with blinded MTX/PBO was restarted.

Results Pt baseline (BL) data were similar between treatment arms except for higher mean Genant-Sharp Scores in the switch group. Of the 556 randomized pts, 423 (222 add-on, 201 switch) completed year 2 and 100 (52 add-on, 48 switch) extended into year 3. Reasons for withdrawal included lack of efficacy (1.8% add-on, 5.1% switch) and adverse events (AEs; 10.1% add-on, 11.6% switch, including 4 and 6 deaths, respectively). Of pts entering into year 2, ∼50% discontinued TCZ after achieving sustained remission and some further stopped other study treatments. Most pts (84.0%) had a subsequent flare, but responded well to TCZ reintroduction (after a median of 90 days). Only a small minority of pts who completed Week 52 (5.9%) achieved drug-free remission. Despite many pts stopping TCZ for some period, radiographic progression was minimal in both groups, with differences favoring add-on pts. SAEs and serious infections per 100 PY were 12.2 and 4.4, respectively, for add-on pts and 15.0 and 3.7, respectively, for switch pts. In pts with normal BL values, ALT elevations >3x ULN were more frequent in add-on pts vs switch pts (14.3% vs 5.4%).

Conclusions Efficacy and safety of TCZ+MTX and TCZ+PBO strategies were comparable, but small differences favored combination therapy. T2T strategies could be successfully implemented with TCZ to achieve sustained remission, after which TCZ was stopped. Biologic-free remission was maintained for a limited time, but most pts eventually flared. TCZ restart led to rapid improvement.


  1. Dougados M, et al. Ann Rheum Dis. 2013;72:43-50.

  2. Dougados M, et al. Ann Rheum Dis. 2014. In Press.

Disclosure of Interest T. Huizinga Consultant for: Abbott, Axis Shield Diagnostics, Biotest AG, BMS, Crescendo Bioscience, Novartis, Pfizer, Roche, Schering-Plough, UCB and Wyeth., P. Conaghan Speakers bureau: BMS, Janssen, Pfizer and Roche., E. Martin-Mola: None declared, G. Schett: None declared, H. Amital: None declared, R. Xavier Consultant for: Merck, Pfizer and Roche., O. Troum Grant/research support: ACT-RAY clinical trial., M. Aassi Employee of: F. Hoffman-La Roche Ltd., C. Bernasconi Consultant for: F. Hoffman-La Roche Ltd., M. Dougados Consultant for: Abbott, Pfizer, Roche and UCB.

DOI 10.1136/annrheumdis-2014-eular.1434

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