Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients

Abstract

ObjectiveAn interim analysis of an all-patient postmarketing surveillance programme in Japan to investigate the safety of tocilizumab for the treatment of rheumatoid arthritis (RA) in the real world.MethodsThis analysis included 3881 patients. Patients received 8 mg/kg of tocilizumab every 4 weeks, and were observed for 28 weeks. Data on baseline characteristics and adverse events (AE) were collected.ResultsTotal and serious AE were reported as 167 and 27 events/100 patient-years, respectively. The most frequent AE and serious AE were infections. Logistic regression analysis identified the following risk factors for the development of serious infection: concurrent or medical history of respiratory disorders; prednisolone dose at baseline ≥5 mg/day; and age ≥65 years. Twenty-five patients died, and the standardised mortality ratio, with the Japanese general population in 2008 as reference, was 1.66, similar to the results from the Japanese cohort study for RA patients.ConclusionsTocilizumab is acceptably safe in the real clinical setting. Tocilizumab needs to be used with consideration of the benefit–risk balance to avoid serious infections in elderly patients and those on high doses of corticosteroids or with a concurrent or medical history of respiratory disorders.

Effectiveness and Safety of Tocilizumab: Postmarketing Surveillance of 7901 Patients with Rheumatoid Arthritis in Japan

“…The safety and effectiveness profiles of TCZ reported here are consistent with the results of the interim analysis of this study 1 . The most common AE and SAE reported in this analysis were infections.…”

“…Multivariate logistic regression analysis identified the following risk factors for serious infection: age ≥ 65 years, longer disease duration (≥ 10 yrs), previous or concurrent respiratory disease, and mean concomitant corticosteroid dose > 5 mg/day (prednisolone equivalent). The risk factors for serious infection identified in our study are similar to the findings reported from the all-patient PMS conducted for infliximab, etanercept, and adalimumab in Japan 1,13,14,15 . Patients with 3 or more of these risk factors had a cumulative incidence of serious infection about 10 times that of patients with no risk factors.…”

“…Additionally, because hepatitis B reactivation has been reported during treatment with other biologics, especially for anti-tumor necrosis factor therapy, careful screening and monitoring are also strongly recommended for patients given TCZ treatment 15 . In our study, the incidence rate of ILD (0.5%) was equivalent to that found in the PMS of infliximab (0.5%) and etanercept (0.6%) in Japan 1,13 . Because infection could be a trigger for the onset of interstitial pneumonia, careful monitoring of infection will be important for patients with a concurrent or medical history of ILD.…”

“…All patients with RA in Japan who started treatment with TCZ between April 2008 and August 2010 were enrolled in our study and monitored during the surveillance period. Interim results covering 3881 patients with RA were previously published 1 . In accordance with the Japanese package insert, TCZ was administered to patients who had an inadequate response to at least 1 antirheumatic agent.…”

Optimal Treatment Strategy for Amyloid A Amyloidosis in Rheumatic Diseases – Anti-Interleukin-6 Receptor Therapy

“…Expectations related to the usefulness of tocilizumab are high. However, an all-case post-marketing survey for tocilizumab (Koike et al, 2010) found that, among patients with progressive renal disorders with multiple organ failure in whom tocilizumab was used for life-saving purposes, complications such as infections and deaths were reported. Therefore, considerable caution is required when tocilizumab is used.…”