Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice
- Vivian P Bykerk1,2,
- Andrew J K Östör3,
- José Alvaro-Gracia4,
- Karel Pavelka5,
- José Andrés Román Ivorra6,
- Winfried Graninger7,
- William Bensen8,
- Michael T Nurmohamed9,
- Andreas Krause10,
- Corrado Bernasconi11,
- Andrea Stancati12,
- Jean Sibilia13
- 1Inflammatory Arthritis Center, Hospital for Special Surgery, New York, USA
- 2Department of Rheumatology, Mount Sinai Hospital, Toronto, Ontario, Canada
- 3Department of Rheumatology, Addenbrookes Hospital, Cambridge, UK
- 4Rheumatology Service, Hospital Universitario de la Princesa, Madrid, Spain
- 5Institute of Rheumatology and Clinic of Rheumatology, Charles University, Prague, Czech Republic
- 6Rheumatology Service, Division of Rheumatology, Hospital Universitario La Fe, Valencia, Spain
- 7Division of Rheumatology, Medical University of Graz, Graz, Austria
- 8DeGroot School of Medicine, McMaster University, Hamilton, Canada
- 9Jan van Breemen Research Institute, VU University Medical Center, Amsterdam, Netherlands
- 10Department of Rheumatology, Medical Centre for Rheumatology Berlin Buch, Berlin, Germany
- 11Biostatistics, Roche, Basel, Switzerland
- 12Global Medical Affairs, Roche, Basel, Switzerland
- 13Department of Rheumatology, CHU Hautepierre, Strasbourg, France
- Correspondence to Vivian Bykerk, Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York, 10021, USA; USA;
Contributors VPB, AKJO, JA-G, KP, JARI, WB, JS were involved in the conception and design of the study, acquisition of data, or analysis and interpretation of data; drafting of manuscript and revising it critically for important intellectual content; final approval of the version to be published. WG was involved in the acquisition of data; revising the manuscript critically for important intellectual content; final approval of the version to be published. MTH was involved in the acquisition and interpretation of data; drafting of manuscript and revising it critically for important intellectual content; final approval of the version to be published. AK was involved in the conception and design of the study, acquisition of data, or analysis and interpretation of data; final approval of the version to be published. CB, AS were involved in the conception and design of the study, analysis and interpretation of data; drafting of manuscript and revising it critically for important intellectual content; final approval of the version to be published.
- Accepted 23 March 2012
- Published Online First 21 May 2012
Objective To evaluate the safety and efficacy of tocilizumab in clinical practice in patients with rheumatoid arthritis (RA) with inadequate responses (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour necrosis factor α inhibitors (TNFis).
Methods Patients—categorised as TNFi-naive, TNFi-previous (washout) or TNFi-recent (no washout) —received open-label tocilizumab (8 mg/kg) every 4 weeks ± DMARDs for 24 weeks. Adverse events (AEs) and treatment discontinuations were monitored. Efficacy end points included American College of Rheumatology (ACR) responses, 28-joint disease activity score (DAS28) and European League Against Rheumatism responses.
Results Overall, 1681 (976 TNF-naive, 298 TNFi-previous and 407 TNFi-recent) patients were treated; 5.1% discontinued treatment because of AEs. The AE rate was numerically higher in TNFi-recent (652.6/100 patient-years (PY)) and TNFi-previous (653.6/100PY) than in TNFi-naive (551.1/100PY) patients. Serious AE rates were 18.0/100PY, 28.0/100PY and 18.6/100PY; serious infection rates were 6.0/100PY, 6.8/100PY and 4.2/100PY, respectively. At week 4, 36.5% of patients achieved ACR20 response and 14.9% DAS28 remission (<2.6); at week 24, 66.9%, 46.6%, 26.4% and 56.8% achieved ACR20/ACR50/ACR70 responses and DAS28 remission, respectively. Overall, 61.6% (TNFi-naive), 48.5% (TNFi-previous) and 50.4% (TNFi-recent) patients achieved DAS28 remission.
Conclusions In patients with RA who were DMARD-IR/TNFi-IR, tocilizumab ± DMARDs provided rapid and sustained efficacy without unexpected safety concerns.
Funding Funding for manuscript preparation was provided by F Hoffmann-La Roche Ltd.
Competing interests VPB has received consulting fees from Amgen, Pfizer, BMS, Roche, UCB; her institution has received grants from Amgen, Pfizer, BMS, UCB, Roche. AJKO has received consulting and expert testimony fees for expert opinion, honoraria for lectures, fees for the development of educational presentations and aids and travel expenses to attend conferences. JA-G has received consulting fees from Roche, BMS, UCB, Pfizer/Wyeth; lecture/speakers bureau fees from Roche, BMS, UCB, Pfizer/Wyeth, MSD/Schering-Plough, Abbott; travel expenses from Roche; and grants to his institution from Roche. KP has received board member fees from Roche, Pfizer, Amgen, UCB; consulting fees from Roche, MSD, Pfizer, UCB, BMS; and lecturer/speaker fees from Roche, MSD, Pfizer, UCB, BMS, Abbott. JARI has received travel expenses from Abbott, Roche; and grants from MSD, Roche. WG has received board member, consulting, and lecture/speaker fees from Roche, BMS, Pfizer, MSD, Abbott, UCB; and consulting fees/honorarium paid to his institution from Roche. WB has received board membership, consulting/honoraria, lecture/speaker fees; and has received grants paid to his institution. MTN has received consulting fees from Abbott, Roche, MSD, BMS, UCB, Wyeth, Sobi; speaker/lecture fees from Abbott, Roche, Pfizer; travel expenses from Roche, MSD; and grants from Roche, Abbott, Pfizer to his institution. AK has received board membership, consulting, lecture/speaker fees and travel expenses from Roche/Chugai. CB has received consulting fees from Roche Global Medical Affairs. AS was an employee of F Hoffmann-La Roche Ltd, Basel, Switzerland. JS has received board membership and consulting fees from Roche, MSD, Abbott, Pfizer, UCB.
Ethics approval Protocol approval by institutional review boards, ethics committees and/or regulatory authorities and patients' written informed consent were obtained in accordance with the Declaration of Helsinki, and good clinical practice was followed.
Provenance and peer review Not commissioned; externally peer reviewed.
Correction notice This article has been corrected since it was published Online First.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/3.0/ and http://creativecommons.org/licenses/by-nc/3.0/legalcode