Background Both herpes zoster (HZ) and malignancies have been reported in patients treated with TNF blockers such as etanercept (ETN). In Japanese patients with RA, information regarding the incidence of HZ and malignancy following long-term treatment with TNF blockers is limited.
Objectives The objective of this study was to analyse the incidence rates (IR) of HZ and malignancy in Japanese patients with RA treated with ETN in order to expand the safety data set available for this patient population.
Methods Data were pooled from 4 clinical trials of ETN in Japanese patients with RA. Two studies were double-blind trials of 10 and 25 mg ETN vs placebo (study 202) or methotrexate (study 315-JA), and were of 12 and 52 weeks duration, respectively. The other 2 studies were open-label, long-term trials of ETN (studies 310-JA and 313-JA) and were of 183 and 134 weeks duration, respectively. Crude IR for HZ and malignancy per 100 patient-years, with 95% confidence intervals (95% CI), were calculated and the rates were stratified by age and time of symptom development.
Results A total of 521 patients with RA were included in this analysis. Mean age was 51.9 years and 81.6% of patients were female. Mean and standard deviation (SD) duration of RA was 5.2 ± 6.5 years, and the mean (SD) disease activity score 28-erythrocyte sedimentation rate was 6.15 ± 1.20. Following ETN treatment, 18 incidences of HZ in 17 patients were reported. The IR/100 years [95% CI] for the entire population was 2.5 [1.45, 4.00]. IR of HZ was highest in the 50–59 age bracket, followed by the 60–69 age bracket (Figure). IR [95% CI] was highest during the first 6 months of treatment with ETN (3.81/100 patient years [1.74, 7.23]) and subsequently declined with a stable cumulative IR seen up to 48 months of treatment (2.50/100 patient years [1.45, 4.00] across the entire treatment period). In addition, 4 incidences of malignancy in 4 patients were reported following treatment with ETN. There was 1 incidence of hypopharyngeal cancer which occurred in the first 6 months of treatment, 2 incidences of breast cancer, each occurring between Months 6–12 of treatment, and 1 incidence of liposarcoma, which occurred between Months 30–36 of treatment with ETN. IR/100 patient years [95% CI] for malignancy was 0.57 [0.15, 1.46].
Conclusions In Japanese patients with RA treated with ETN, increased IR of HZ in patients aged over 50 was observed. This trend is consistent with previous observations in the Japanese general population. IR of HZ was similar to that seen in a study of Japanese patients with RA treated with the IL-6 blocker tocilizumab (2.29/100 patient years),1 and might be higher compared with a large cohort study of Japanese patients with RA (2005–2010) where only 3% of patients used a biological treatment for RA (0.91/100 patient years).2 Malignancies occurred in a small number of patients with limited exposure, and there was no increase in the cumulative IR of malignancy during the treatment period.
Tsutomu Takeuchi and Naonobu Sugiyama are equally credited first authors.
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Disclosure of Interest T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd.,SymBio, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co.,Ltd., Celtrion, Nipponkayaku Co.Ltd, N. Sugiyama Shareholder of: Pfizer, Employee of: Pfizer, N. Miyasaka Grant/research support from: AbbVie, Astellas, Chugai, Eisai, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation and Takeda., Y. Morishima Shareholder of: Pfizer, Employee of: Pfizer, H. Yuasa Shareholder of: Pfizer, Employee of: Pfizer, N. Sugiyama Shareholder of: Pfizer, Employee of: Pfizer