Effectiveness and safety of Mizoribine for the treatment of IgG4-related Disease: A Retrospective Cohort Study.

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Patients with IgG4-Related Disease (IgG4RD) usually require steroid-sparing agents due to relapse with tapering glucocorticoids (GC). The aim of this study was to determine the efficacy and safety of Mizoribine (MZR) among IgG4RD, which inhibits inosine monophosphate dehydrogenase, a rate-limiting enzyme in the de novo pathway of purine synthesis.We retrospectively reviewed records of IgG4RD patients at the Immuno-Rheumatology Center in St. Luke's International Hospital, Tokyo, Japan. Patients were classified into the MZR combination group, and those treated with GCs alone or with other immunosuppressants were included in the control group. Disease exacerbation, GC dose, IgG-IgG4 titre, and adverse events were evaluated using univariate analyses, including the Kaplan-Meier method. The Cox proportional hazard model was used to evaluate risk factors for exacerbation.A total of 14 and 29 cases were included in the MZR combination and control groups, respectively. Multiple organ involvement (≥3 organs) was significantly more frequent in the MZR combination treatment group (10 [71.4%] vs 9 [31.0%], p= 0.021). Kaplan-Meier analysis revealed a significant reduction in exacerbation in patients with multiple organ involvement (p< 0.001), but not in total (p= 0.42). The adjusted hazard ratios of MZR use and multiple organ involvement for exacerbation were 0.34[0.12-1.01] (p= 0.052), and 3.51[1.29-9.51] (p= 0.014). The cumulative GC dose tended to be lower in the MZR combination group (1448[1003, 1642] vs 2179[1264, 3425]; p= 0.09).MZR showed a significant steroid-sparing effect and decrease in exacerbation among IgG4RD patients with multi-organ involvement. MZR could be a treatment option for IgG4RD.


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Authors: Sho Fukui, Satoshi Kawaai, Takehiro Nakai, Masei Suda, Yukihiko Ikeda, Atsushi Nomura, Hiromichi Tamaki, Mitsumasa Kishimoto, Sachiko Ohde, Masato Okada

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