Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis

Takeuchi, Tsutomu; Tatsuki, Yoshihiko; Nogami, Yashiro; Ishiguro, Naoki; Tanaka, Yoshiya; Yamanaka, Hisashi; Kamatani, Naoyuki; Harigai, Masayoshi; Ryu, Junnosuke; Inoue, Kazuhiko; Kondo, Harumi; Inokuma, Shigeko; Ochi, Takahiro; Koike, Takao

doi:10.1136/ard.2007.072967

Cited by 381 publications

(247 citation statements)

References 19 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%

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%

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%

“…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.…”

Section: Rheumatologysupporting

confidence: 52%

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

Koike

Harigai²,

Inokuma³

et al. 2013

J Rheumatol

182

105

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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 Japan, a strict postmarketing surveillance program was implemented that mandated the registration of all patients with RA receiving infliximab, with a tracking period of 6 months for each patient. Of the 5,000 patients tracked, this postmarketing surveillance program identified 108 patients (2.2%) with bacterial pneumonia and 14 patients (0.3%) with tuberculosis (7). Notably, 22 patients (0.4%) with Pneumocystis jiroveci pneumonia (PCP) were identified in the same postmarketing surveillance program (7), a much higher number than was found in corresponding studies in the US (3).…”

Section: Introductionmentioning

confidence: 74%

“…The incidences of PCP during the postmarketing surveillance programs of infliximab and etanercept in Japan were 0.4% and 0.23%, respectively (7,8). The corresponding incidence reported in the US is ϳ0.01% (25).…”

Section: Discussionmentioning

confidence: 99%

Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab: A retrospective review and case–control study of 21 patients

Komano¹,

Harigai²,

Koike³

et al. 2009

Arthritis & Rheumatism

148

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Objective. To establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan. Methods. Data from patients with RA (n ‫؍‬ 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case-control study to compare patients with and without PCP were performed. Results. The median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground-glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived. Conclusion. PCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy.

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Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis

Cited by 381 publications

References 19 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

Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab: A retrospective review and case–control study of 21 patients

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