Prednisolone improves walking in Japanese Duchenne muscular dystrophy patients

Abstract

We evaluated the long-term efficacy of prednisolone (PSL) therapy for prolonging ambulation in Japanese patients with genetically confirmed Duchenne muscular dystrophy (DMD). There were clinical trials have shown a short-term positive effect of high-dose and daily PSL on ambulation, whereas a few study showed a long-term effect. Especially in Japan, "real-life" observation was lacking. We utilized the national registry of muscular dystrophy in Japan for our retrospective study. We compared the age at loss of ambulation (LOA) between patients in PSL group and those in without-PSL group. Out of 791 patients' in the Remudy DMD/BMD registry from July 2009 to June 2012, 560 were matched with inclusion criteria. Of the 560, all were genetically confirmed DMD patients, 245 (43.8 %) of whom were treated with PSL and 315 (56.2 %) without PSL. There was no difference between the two groups regarding their mutational profile. The age at LOA was significantly greater (11 month on average) in the PSL group than in the without-PSL group (median, 132 vs. 121 months; p = 0.0002). Although strictly controlled clinical trials have shown that corticosteroid therapies achieved a marked improvement in ambulation, discontinuation of the drug due to intolerable side effects led to exclusion of clinical trial participants, which is considered as unavoidable. In our study, patients were not excluded from the PSL group, even if they discontinued the medication shortly after starting it. The results of our study may provide evidence to formulate recommendations and provide a basis for realistic expectations for PSL treatment of DMD patients in Japan, even there are certain limitations due to the retrospectively captured data in the registry.

Fig. 1

Selection of DMD patients from the Remudy database for this study. *1: These 46 patients included out-of-frame mutations (n = 7) and nonsense mutations (n = 7). *2: Three patients met (2) and (3) of our exclusion criteria. *3: Twenty-three patients met (1) and (2) of our exclusion criteria. DMD Duchenne muscular dystrophy, PSL prednisolone, Remudy Registry of Muscular Dystrophy

Fig. 2

Time to loss of ambulation in the PSL group and without-PSL group determined by the Kaplan–Meier method. *Three patients in the PSL group and. **Four patients in the without-PSL group were excluded because their ambulation status was unknown. The PSL group had 242, 136 and 8 ambulant patients at 60, 120 and 180 months of age, respectively. The without-PSL group had 311, 145 and 10 ambulant patients at 60, 120 and 180 months of age, respectively. PSL prednisolone, HR hazard ratio