Postmarketing Surveillance of the Safety and Effectiveness of Etanercept in Japan

Koike, Takao; Harigai, Masayoshi; Inokuma, Shigeko; Inoue, Kazuhiko; Ishiguro, Naoki; Ryu, Junnosuke; Takeuchi, Tsutomu; Tanaka, Yoshiya; Yamanaka, Hisashi; Fujii, Koichi; Freundlich, Bruce; Suzukawa, Michio

doi:10.3899/jrheum.080791

Cited by 171 publications

(112 citation statements)

References 16 publications

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“…Among the latter, six patients discontinued due to pneumonia. Pneumonia was the most frequent adverse event observed in previous Japanese post-marketing surveillance (PMS) evaluation of infliximab [40] and etanercept [27], which is consistent with the results of our study. However, it should be noted that susceptibility to infection is an important concern not only in association with anti-TNF therapies but also with the anti–IL-6 activity of tocilizumab.…”

Section: Discussionsupporting

confidence: 93%

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Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study)

et al. 2010

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Tocilizumab, a humanized monoclonal antibody to the interleukin 6 (IL-6) receptor, was approved for use as rheumatoid arthritis (RA) therapy in Japan in 2008, but its efficacy and tolerability in daily practice has not yet been reported. We report the results of a multicenter retrospective study on the efficacy and safety of tocilizumab involving all patients (n = 229) who were started on tocilizumab therapy at three rheumatology institutes in Japan from April 2008 through to March 2009. Tocilizumab was infused every 4 weeks at a dose of 8 mg/kg according to the drug labeling. Among the 229 patients, 55% concomitantly received methotrexate (MTX) and 63% had previously received anti-tumor necrosis factor (TNF) therapy. Average disease activity score (DAS) 28 of all 229 patients significantly decreased from 5.70 to 3.25 after 24 weeks of therapy. A European League Against Rheumatism (EULAR) good response and DAS28 remission was achieved in 57.4 and 40.7% of the patients, respectively, at 24 weeks. White blood cell counts significantly decreased and liver enzymes and total cholesterol slightly but significantly increased; however, liver enzyme levels did not increase in patients without MTX. Tocilizumab was discontinued in 47 cases (20.5%) due to lack of efficacy (5.2%), adverse events (11.4%), and other reasons (3.9%). The overall retention rate at 24 weeks was 79.5%. Based on these results, we conclude that tocilizumab therapy in daily rheumatology practice appears to be highly efficacious and well tolerated among active RA patients, including the anti-TNF therapy-refractory population. Tocilizumab infusion is therefore applicable not only as an alternative approach for anti-TNF therapy-resistant patients, but also as primary biologic therapy for active RA patients.

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Section: Discussionsupporting

confidence: 93%

“…Government regulations have limited the maximum dose of MTX to 8 mg/week in Japan; however, many rheumatologists prescribe higher MTX doses off-label [24, 27]. It is remarkable that such low-dose MTX potentiates tocilizumab action in severe RA patients.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study)

et al. 2010

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“…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.…”

Section: Rheumatologysupporting

confidence: 79%

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

Koike

Harigai²,

Inokuma³

et al. 2013

J Rheumatol

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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.

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“…In addition, we have found in the literature four cases of fatal pulmonary NTM infections that occurred during anti-TNFα therapy for rheumatic diseases [30–33]. Until now, however, no fatal case of NTM disease has been reported in the Japanese postmarketing surveillance of biological therapy for RA [34–37]. In the present study, therapeutic responses to anti-NTM therapy were also favorable.…”

Section: Discussionsupporting

confidence: 65%

Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan

et al. 2011

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ObjectiveThis study was performed to evaluate the radiological features of and therapeutic responses to pulmonary disease caused by nontuberculous mycobacteria (NTM) in the setting of biological therapy for rheumatoid arthritis (RA).MethodsWe conducted a retrospective chart review of 13 patients from multiple centers who had developed pulmonary NTM disease during biological therapy for RA, including infliximab, etanercept, adalimumab, and tocilizumab.ResultsMost cases were asymptomatic or resulted in only common-cold-like symptoms. Abnormalities in computed tomography (CT) imaging were protean and frequently overlapped. The most predominant pattern was nodular/bronchiectatic disease (six cases), followed by alveolar infiltrate (three cases), cavitary disease (two cases), and pulmonary nodules (two cases). In most cases, pulmonary NTM disease had spread from a preexisting lesion; in particular, bronchial/bronchiolar abnormalities. In three cases, one or more nodular lesions with or without calcification were a focus of disease. Following the discontinuation of biological agents, most patients responded to anti-NTM therapy. Two patients showed no exacerbation in the absence of any anti-NTM therapy. In one patient, restarting tocilizumab therapy while continuing to receive adequate anti-NTM therapy produced a favorable outcome. In two other patients with a previous history of pulmonary NTM disease, introducing biological therapy led to recurrence, but anti-NTM therapy was effective in these patients.ConclusionCT abnormalities of pulmonary NTM disease in RA patients receiving biological therapy were variable, but were not unique to this clinical setting. NTM disease can spread from preexisting structural abnormalities, even if they are minute. Contrary to our expectations, the therapeutic outcomes of pulmonary NTM disease were favorable in these patients.

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Postmarketing Surveillance of the Safety and Effectiveness of Etanercept in Japan

Cited by 171 publications

References 16 publications

Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study)

Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study)

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

Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan

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