Background Patients with polymyalgia rheumatica (PMR) often need long-term steroid treatment, which raises concern for chronic side effects of steroid. In the 2015 ACR/EULAR recommendations for the management of PMR, methotrexate (MTX) was recommended as a 1st line agent for steroid sparing. However, elderly patients often cannot tolerate MTX. Mizoribine (MZR), an inosine monophosphate dehydrogenase inhibitor, has been widely used in the field of organ transplantations in Japan. We have reported the efficacy and the excellent safety of MZR in the rheumatology field (1), and its steroid sparing effect as well (2). The role of MZR on PMR treatment has not been clarified.
Objectives To evaluate efficacy and safety of MZR compared to MTX in terms of steroid-sparing effect in PMR.
Methods The study design was a retrospective single-institution case series analysis. We searched for all PMR patients who were diagnosed as PMR at St. Luke's International Hospital from 1998 to 2014. The inclusion criteria were fulfillment of the 1979 classification criteria of PMR, and receiving treatment with prednisone in combination with either MTX or MZR. The exclusion criteria were the diagnosis of giant cell arteritis or other connective tissue diseases, use of both MTX and MZR, and use of other immunosuppressants. The following data were collected; total prednisone dose that participants had received within 48 weeks after stating MTX or MZR, the dose of the steroid on 48 weeks after starting MTX or MZR, and side effects profile.
Results A total of 24 participants (14 for MZR group; 10 for MTX group) were included. The cumulative prednisone dose in 0–48 weeks was 2154 (1181 to 3127) mg in MTX group and 1940 (1379 to 2502) mg in MZR group, and the difference between the arms was -214 mg (a one-sided 90% CI: -1019 to 591.7). The dose of the steroid on 48 weeks after starting steroid sparing agent was 4.17 mg (95%CI: 1.64 to 3.90) in MTX arm and 2.71 mg (95% CI: 1.78 to 6.55) in MZR arm, seeming in favor of MZR although statistically not significant (P=0.20). Side effect profile was as follows; in MTX group, 3 out of 10 patients experienced a transient elevation in liver enzymes and 1 patient developed gastrointestinal symptom which lead to MTX withdrawal. In MZR group, one patient experienced a transient elevation in liver enzymes, 1 patient developed gastrointestinal symptom which were tolerable, and one patient was hospitalized due to pneumonia requiring 1 week of iv antibiotics, which lead to MZR withdrawal.
Conclusions MZR may be non-inferior or may be even superior to methotrexate in terms of steroid sparing effects on PMR patients, although statistically not significant due to small sample size. MZR generally has fewer side effects than MTX. Further investigation with a larger number of patients in RCT is needed for confirmation.
Nomura, A., et al. "Efficacy and safety of multitarget therapy with mizoribine and tacrolimus for systemic lupus erythematosus with or without active nephritis." Lupus 21.13 (2012): 1444–1449.
Rokutanda, R., et al. "Safety and efficacy of mizoribine in patients with connective tissue diseases other than rheumatoid arthritis." Rheumatology international 34.1 (2014): 59–62.
Disclosure of Interest None declared