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Tocilizumab for the treatment of polyarteritis nodosa: a systematic literature review
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  1. Mitsuhiro Akiyama,
  2. Yuko Kaneko,
  3. Tsutomu Takeuchi
  1. Division of Rheumatology, Department of Internal Medicine, Keio University - Shinanomachi Campus, Shinjuku-ku, Tokyo, Japan
  1. Correspondence to Dr Yuko Kaneko, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan; ykaneko.z6{at}keio.jp

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We read the paper by Rimar et al1 in your journal with great interest. They reported the case with refractory polyarteritis nodosa treated with tofacitinib, a janus kinase inhibitor, successfully. As shown in their paper, recent advances in the era of biologic agents have improved the management of difficult-to-treat cases dramatically. Considering that tofacitinib blocks interleukin (IL)-6-mediated signalling pathway through inhibiting janus kinase 1, inhibiting IL-6 cascade may also be effective in polyarteritis nodosa. In this regard, tocilizumab, a biologic agent targeting IL-6 receptor, has shown its efficacy in a variety of diseases such as rheumatoid arthritis, adult-onset Still’s disease, large-vessel vasculitis and Behcet’s disease.2–5 Although the precise pathogenesis of polyarteritis nodosa remains unclear, serum IL-6 levels correlate with disease severity, suggesting the involvement of IL-6 in the disease process.6 Therefore, we assume that tocilizumab may benefit polyarteritis nodosa as a therapeutic option.

To investigate the effectiveness and safety profile of tocilizumab in patients with polyarteritis nodosa, we performed a systematic literature review from the inception dates until 23 July 2020. We used the PubMed database to identify all English publications using the Medical Subject Heading ‘polyarteritis nodosa’ and ‘tocilizumab’ and identified 13 potentially relevant articles. Among them, seven were excluded due to the following: four reviews, two duplicates and one non-related topic. Eventually, a total of 11 cases with polyarteritis nodosa treated with tocilizumab were identified from six articles (table 1).7–12 The median age of the cases was 35 years old (range: 3–70), with equal sex distribution. The median disease duration at tocilizumab treatment was 38 months (range: 3–120). Clinical symptoms varied through the cases (online supplementary table 1). All patients showed high levels of serum C reactive protein (median, 19.7 mg/dL). As shown in table 1, the reasons for initiating tocilizumab were the following: nine cases with refractory to and/or relapsing clinical course by prior immunosuppressive treatments such as cyclophosphamide (n=6), methotrexate (n=4), mycophenolate mofetil (n=2), azathioprine (n=2), tacrolimus (n=1), anti-tumour necrosis factor agents (n=2), rituximab (n=1) and anakinra (n=1). In the other two cases, tocilizumab was initiated as a primary induction therapy. Tocilizumab was used as the intravenous administration at a dose of 8 mg/kg every 4 weeks in seven cases and every 2 weeks in one case, at a dose of 10 mg/kg every 4 weeks in one case and subcutaneous administration at a dose of 162 mg weekly in two cases. In seven cases, tocilizumab was used in combination with high-dose glucocorticoids (table 1). The median observation period after tocilizumab treatment was 12 months (range: 6–37). In all cases, tocilizumab rapidly improved clinical manifestations, mostly within a week, and glucocorticoids could be successfully tapered. All cases achieved asymptomatic condition at last visit. Glucocorticoids were completely stopped in three cases, while eight cases were receiving only low dose (≤5 mg/day) at last visit (table 1). No new safety signal or adverse event was reported.

Table 1

Characteristics and outcome of 11 patients with polyarteritis nodosa treated with tocilizumab

As this literature review was based on case reports, in which positive results are inclined to be published, potential publication bias can exist. Further, the number of case reports was small due to the rarity of the disease. Nevertheless, tocilizumab is effective in cases of refractory/relapsing polyarteritis nodosa and showed its glucocorticoid-sparing effect. It could even achieve glucocorticoid-free in some cases. Generally, the prognosis of polyarteritis nodosa is poor, showing the 5-year survival rate as 13% if untreated and as 80% even if treated.13 Our study along with the one by Rimar et al would shed light on the management of this rare disease by biologic agents to improve their prognosis. Future prospective randomised controlled trials are desired to confirm our results.

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Footnotes

  • Contributors MA, YK and TT wrote and discussed the manuscript. All authors approved the final version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests MA reports no conflicts of interest relevant to this article. YK has received grants or speaker fees from AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi and UCB. TT has received research grants or speaking fees from Astellas Pharma Inc, Bristol–Myers KK, Chugai Pharmaceutical Co, Ltd, Daiichi Sankyo Co, Ltd, Takeda Pharmaceutical Co, Ltd, Teijin Pharma Ltd, AbbVie GK, Asahi Kasei Pharma Corp, Mitsubishi Tanabe Pharma, Astra Zeneca KK, Eli Lilly Japan KK, Novartis Pharma KK, AbbVie GK, Nippon Kayaku Co Ltd, Janssen Pharmaceutical KK, Taiho Pharmaceutical Co, Ltd and Pfizer Japan Inc.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval Local ethics committee approval was not required because this study was based on published data.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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