Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study
- 1Osaka University, Osaka, Japan
- 2Tokyo Medical and Dental University, Tokyo, Japan
- 3University of Tokyo, Tokyo, Japan
- 4Toho University Omori Medical Center, Tokyo, Japan
- 5Saitama Medical Center/School, Saitama, Japan
- Correspondence to Dr N Nishimoto, Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamada-oka, Suita, Osaka 565-0871, Japan;
- Accepted 29 October 2008
- Published Online First 19 November 2008
Objectives: To evaluate the safety and efficacy of 5-year, long-term tocilizumab monotherapy for patients with rheumatoid arthritis.
Methods: In an open-label, long-term extension trial following an initial 3-month randomised phase II trial, 143 of the 163 patients who participated in the initial blinded study received tocilizumab monotherapy (8 mg/kg) every 4 weeks. Concomitant therapy with non-steroidal anti-inflammatory drugs and/or oral prednisolone (10 mg daily maximum) was permitted. All patients were evaluated with American College of Rheumatology (ACR) improvement criteria, disease activity score (DAS) in 28 joints, and the European League Against Rheumatism response, as well as for safety issues.
Results: 143 patients were enrolled in the open-label, long-term extension trial and 94 (66%) patients had completed 5 years as of March 2007. 32 patients (22%) withdrew from the study due to adverse events and one patient (0.7%) due to unsatisfactory response. 14 patients withdrew because of the patient’s request or other reasons. The serious adverse event rate was 27.5 events per 100 patient-years, with 5.7 serious infections per 100 patient-years, based on a total tocilizumab exposure of 612 patient-years. Of the 88 patients receiving corticosteroids at baseline, 78 (88.6%) were able to decrease their corticosteroid dose and 28 (31.8%) discontinued corticosteroids. At 5 years, 79/94 (84.0%), 65/94 (69.1%) and 41/94 (43.6%) of the patients achieved ACR20, ACR50, and ACR70 improvement criteria, respectively. Remission defined as DAS28 less than 2.6 was achieved in 52/94 (55.3%) of the patients.
Conclusion: In this 5-year extension study, tocilizumab demonstrated sustained long-term efficacy and a generally good safety profile.
Funding This work was financially supported by Chugai Pharmaceutical Co, Ltd, Tokyo, Japan.
Competing interests NN has served as a consultant to and received honoraria from Chugai Pharmaceuticals, the manufacturer of tocilizumab. NN also works as a scientific advisory board of Hoffmann-La Roche who develops tocilizumab in collaboration with Chugai Pharmaceutical Co Ltd. The other authors have no competing interests.
Ethics approval Ethics approval was obtained.
Patient consent Obtained.