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Current clinical evidence of tocilizumab for the treatment of ANCA-associated vasculitis: a prospective case series for microscopic polyangiitis in a combination with corticosteroids and literature review

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Abstract

The purpose of this study is to report the efficacy and safety of a combination of tocilizumab (TCZ) and high-dose corticosteroid (CS) in two patients with microscopic polyangiitis (MPA) and review the published current clinical evidence on TCZ in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), except for large vessel vasculitis (LVV) and polymyalgia rheumatica (PMR). Two MPA patients were treated with TCZ at 8 mg/kg every month for 1 year and CS (prednisolone 1 mg/kg/day for 2 weeks, followed by tapering) in a prospective single-arm, single-center, cohort, open-label pilot study (UMIN clinical trials: 000012072). We performed a systematic literature search (PubMed and ICHUSHI [Japan Medical Abstracts Society] until June 30, 2017) to identify published reports on patients with all vasculitis other than LVV/PMR, who were treated with TCZ. We successfully treated the first patient. However, the other patient had serious infection probably associated with the combination of TCZ and high-dose CS. The literature review identified 22 reports with a total of 34 patients who received TCZ for AAV, rheumatoid vasculitis, and other types of vasculitis, in addition to our patients. In 15 of 17 patients (88.2%) with primary and secondary AAV, especially MPA, TCZ induced clinical remission, although TCZ use for rheumatoid vasculitis and vasculitis with mucocutaneous lesions is controversial. This study suggested that TCZ therapy is a potential treatment strategy for patients with AAV. However, TCZ combined with high-dose of CS might not be an appropriate treatment. Future studies are needed to confirm our findings.

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Acknowledgements

The authors thank all clinical research assistants in the Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, including Izumi Ohshima, Masami Sato, Mayumi Suzuki, Miyuki Suzuki, Takashi Kukita, Machiko Kawamura, and Megumi Sawada.

The authors also thank colleagues in the Department of Nephrology and Hypertension for taking renal biopsies, in the Department of Diagnostic Pathology for the helpful interpretation of pathological findings, which were all affiliated to Saitama Medical Center, Saitama Medical University.

The authors would like to thank Enago (www.enago.jp) for the English language review.

Author information

Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan

    Ryota Sakai, Tsuneo Kondo, Takahiko Kurasawa, Ayumi Okuyama, Kentaro Chino, Akiko Shibata, Yusuke Okada, Hirofumi Takei, Hayato Nagasawa & Koichi Amano

  2. Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo, Japan

    Ryota Sakai

  3. Department of Internal Medicine, Yunomoto Memorial Hospital, Kagoshima, Japan

    Eiko Nishi

  4. Nagasawa Clinic, Saitama, Japan

    Hayato Nagasawa

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  1. Ryota Sakai
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  2. Tsuneo Kondo
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  3. Takahiko Kurasawa
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  4. Eiko Nishi
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  5. Ayumi Okuyama
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  9. Hirofumi Takei
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Contributions

R.S. drafted the manuscript, figures, and tables, with all authors contributing to the writing and providing advice. R.S. and K.A. conceived and designed the protocol of treatment for the pilot study. All authors were responsible for the clinical care of the patients as well as data analysis.

Corresponding author

Correspondence to Ryota Sakai.

Ethics declarations

The treatment protocol and the trial were performed according to the guidelines stipulated by the World Medical Declaration of Helsinki and the Ethical Guidelines for Clinical Research in Japan (revised in 2008). This pilot study received ethical approval from the institutional review board (application no. 877), and was registered in the UMIN clinical trials registry (UMIN: 000012072).

Conflict of interest

K.A. has received a research grant from Chugai Pharmaceutical Co. Ltd. and honoraria from Pfizer Japan Inc. and Mitsubishi-Tanabe Pharma. The other authors have no conflicts of interest to declare. This research was not supported by any specific grant from any funding agency in public, commercial, or non-profit sectors.

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Sakai, R., Kondo, T., Kurasawa, T. et al. Current clinical evidence of tocilizumab for the treatment of ANCA-associated vasculitis: a prospective case series for microscopic polyangiitis in a combination with corticosteroids and literature review. Clin Rheumatol 36, 2383–2392 (2017). https://doi.org/10.1007/s10067-017-3752-0

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