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

Abstract

Objective.An all-patient postmarketing surveillance program was conducted to evaluate the safety and effectiveness of tocilizumab (TCZ) for rheumatoid arthritis (RA) in the real-world clinical setting in Japan.Methods.Patients received 8 mg/kg TCZ every 4 weeks and were observed for 28 weeks. Data were collected on patient characteristics, and drug safety and effectiveness.Results.A total of 7901 patients were enrolled. Percentages of total and serious adverse events (AE) were 43.9% and 9.6%, respectively. The most common serious AE were infections (3.8%). Logistic regression analysis identified the following risk factors for the development of serious infection: age ≥ 65 years, disease duration ≥ 10 years, previous or concurrent respiratory disease, and concomitant corticosteroid dose > 5 mg/day (prednisolone equivalent). The incidence rate of serious infections in patients with ≥ 3 risk factors was 11.2%, compared with 1.2% for patients without risk factors. The Week 28 rates of 28-joint Disease Activity Score–erythrocyte sedimentation rate remission, Boolean remission, and European League Against Rheumatism (EULAR) Good Response were 47.6%, 15.1%, and 59.4%, respectively. Contributing factors for effectiveness were body weight ≥ 40 kg, less advanced RA, no previous biologics, no concomitant corticosteroids or nonsteroidal antiinflammatory drugs, and low disease activity at baseline. From the benefit-risk balance analysis, patients with a high probability of remission and a low probability of developing serious infection were most likely to have less advanced RA and to have not received biologics previously.Conclusion.These data confirm the safety and effectiveness of TCZ in patients with RA in the real-world clinical setting in Japan and identify factors that contribute to the successful use of TCZ for RA.

Longterm Safety of Tocilizumab: Results from 3 Years of Followup Postmarketing Surveillance of 5573 Patients with Rheumatoid Arthritis in Japan

“…This report refers to the 3-year extension to the 28-week all-patient PMS program evaluating intravenous TCZ in patients with RA in Japan 9 . This longterm extension study was mandated by the Japanese Health Authority, as was the initial all-patient PMS.…”

“…The PMS study protocol has been described 9 . Information on the development of fatal events, serious infections, malignancies, GI perforations, and serious cardiac dysfunction was collected from case report forms and coded using the Medical Dictionary for Regulatory Activities (version 16.1).…”

“…On the basis of these results, TCZ received marketing approval for patients with RA in more than 100 countries. Upon approval, the initial safety and effectiveness of TCZ in the Japanese real-world clinical setting were evaluated in the all-patient postmarketing surveillance (PMS) program with a 28-week followup period 9 . Results of this PMS showed that the overall incidence rate of serious infections was comparable with that of phase III studies, and patients with more risk factors [age > 65 yrs, disease duration ≥ 10 yrs, previous or concurrent respiratory disease, and concomitant corticosteroid dose > 5 mg/day (prednisolone equivalent)] had a higher incidence of serious infections.…”

Biological Therapy and Infection in Rheumatoid Arthritis Patients: Modern Aspects

“…В ходе РКИ и продолженных открытых исследований частота СКИ, развивавшихся при лечении тоцилизумабом (ТЦЗ), колебалась в пределах 4,4-9,0 на 100 пациенто-лет [29][30][31][32][33][34][35][36] и была аналогичной таковой у больных, получав-ших иФНО-α. При увеличении суточной дозы с 4 до 8 мг/кг вероятность развития СКИ повышалась в 2,33 раза [37].…”

“…При увеличении суточной дозы с 4 до 8 мг/кг вероятность развития СКИ повышалась в 2,33 раза [37]. Основными факторами риска развития СКИ были возраст старше 65 лет (ОР 1,54 р=0,0415), длительность болезни более 10 лет (ОР 1,8 р=0,0052), предшествующая или сопутствующая патология дыхательной системы (ОР 1,9 р=0,002) и суточная доза ГК>5 мг (ОР 2,8 р=0,0004) [33]. Также сходной c иФНО-α была структура инфекционных осложнений, которые включали Пн, флегмону, Herpes zoster-инфекцию, бактериальный артрит, реактивацию латентных инфекций, в т. ч. микобактериальных и т. д. В отдельных случаях СКИ приводили к летальному исходу.…”