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Clinical Trial
. 2009 Oct;68(10):1580-4.
doi: 10.1136/ard.2008.092866. Epub 2008 Nov 19.

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

N Nishimoto  1 , N Miyasaka, K Yamamoto, S Kawai, T Takeuchi, J Azuma
Affiliations
Clinical Trial

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

N Nishimoto et al. Ann Rheum Dis. 2009 Oct.

Abstract

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.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Kaplan–Meier estimate of the probability of the patients remaining on study. Treatment time was calculated beginning with the first infusion of tocilizumab at any dose, excluding the time receiving placebo.
Figure 2
Figure 2
Change in serum total cholesterol, high-density lipoprotein (HDL) cholesterol, neutrophil counts, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Values are means. Bars indicate SD. BL, baseline.
Figure 3
Figure 3
Percentage of responders according to the American College of Rheumatology improvement criteria and the disease activity score in 28 joints (DAS28) as well as the mean change in modified health assessment questionnaire (MHAQ) scores, number of tender joints, number of swollen joints, C-reactive protein (CRP) and haemoglobin. BL, baseline.
See this image and copyright information in PMC

References

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