Objective To evaluate the prognosis and progression of spinal and bulbar muscular atrophy (SBMA), a rare X-linked motor neuron disorder caused by trinucleotide repeat expansion in the AR (androgen receptor) gene, after long-term androgen suppression with leuprorelin acetate treatment.
Methods In the present natural history-controlled study, 36 patients with SBMA treated with leuprorelin acetate for up to 84 months (leuprorelin acetate-treated group; LT group) and 29 patients with SBMA with no specific treatment (non-treated group; NT group) were analysed. Disease progression was evaluated by longitudinal quantitative assessment of motor functioning using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and the modified Norris score. In addition, we selected two major clinical endpoint events, namely the occurrence of pneumonia requiring hospitalisation and death, to evaluate disease prognosis following long-term leuprorelin acetate treatment.
Results In our analysis of the longitudinal disease progression using the random slope model, we observed a significant difference in the ALSFRS-R total score, the Limb Norris Score, and the Norris Bulbar Score (p=0.005, 0.026 and 0.020, respectively), with the LT group exhibiting a slower per-12-months decline compared with the NT group. As for the event analysis, the prognosis of the LT group was better in comparison to the NT group as for the event-free survival period (p=0.021).
Conclusion Long-term treatment with leuprorelin acetate appears to delay the functional decline and suppress the incidence of pneumonia and death in subjects with SBMA.
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Contributors A Hashizume, MK, GS: drafting/revising manuscript, conceptualisation and design of the study, research project execution, and analysis and interpretation of data. KS, YH, SY, TI, HB: revising manuscript and research project execution. A Hirakawa: drafting/revising manuscript, and analysis and interpretation of data.
Funding This work was supported by Grant in Aids (KAKENHI) from Ministry of Education, Culture, Sports, Science, and Technology of Japan (Nos. 26293206, 26670440 and 16K15480); grants from Japan Agency for Medical Research and Development (Nos. 15ek0109025 and 15ek0109165).
Competing interests None declared.
Patient consent The present study aimed to analyse two independent study groups of the SBMA. One of these two studies was registered, UMIN000000474.
Ethics approval Nagoya University Hospital Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.