Optimal dose of intravenous cyclophosphamide during remission induction therapy in ANCA-associated vasculitis: A retrospective cohort study of J-CANVAS

Hideaki Sofue, Takashi Kida, Aiko Hirano, Satoshi Omura, Masatoshi Kadoya, Daiki Nakagomi, Yoshiyuki Abe, Naoho Takizawa, Atsushi Nomura, Yuji Kukida, Naoya Kondo, Yasuhiko Yamano, Takuya Yanagida, Koji Endo, Shintaro Hirata, Kiyoshi Matsui, Tohru Takeuchi, Kunihiro Ichinose, Masaru Kato, Ryo YanaiYusuke Matsuo, Yasuhiro Shimojima, Ryo Nishioka, Ryota Okazaki, Tomoaki Takata, Takafumi Ito, Mayuko Moriyama, Ayuko Takatani, Yoshia Miyawaki, Toshiko Ito-Ihara, Nobuyuki Yajima, Takashi Kawaguchi, Kazuki Fujioka, Wataru Fujii, Takahiro Seno, Makoto Wada, Masataka Kohno, Yutaka Kawahito*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Objectives: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis. Methods: We retrospectively assessed patients with antibody-associated vasculitis who received IVCY every 2–3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5–12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes was also evaluated. Results: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94–19.8) for VLD and 5.1 (95% CI 1.21–21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly. Conclusion: Low-dose IVCY (7.5–12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg).

Original languageEnglish
Pages (from-to)767-774
Number of pages8
JournalModern Rheumatology
Volume34
Issue number4
DOIs
StatePublished - 2024/07/01

Keywords

  • Antineutrophil cytoplasmic antibody-associated vasculitis
  • cyclophosphamide
  • intravenous cyclophosphamide
  • restricted cubic spline
  • severe infection

ASJC Scopus subject areas

  • General Medicine

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