Abstract
The incidence and prevalence of Parkinson's disease (PD) is expected to raise dramatically over the next decades. Gender-related differences are not yet widely recognized, particularly regarding the response to dopaminergic medications. To analyse gender differences in the clinical effects of safinamide, compared to placebo, in Chinese PD patients of the pivotal XINDI trial. The XINDI study was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Patients were followed for 16 weeks receiving safinamide or placebo as add-on to levodopa. The primary efficacy endpoint was the change in the mean total daily OFF time. Secondary efficacy endpoints included total daily ON time, ON time with no/non-troublesome dyskinesia, Unified Parkinson's Disease Rating Scale and Parkinson's Disease Questionnaire-39 items. A post-hoc analysis was performed to describe the efficacy of safinamide in both genders on motor symptoms, motor fluctuations and quality of life. 128 (42%) out of 305 patients enrolled were women and 177 (58%) men. Our additional analyses of the XINDI study have shown that safinamide, compared to placebo, was associated with improvements in motor symptoms, motor fluctuations and quality of life in both genders, with some differences in the response that did not reach statistical significance, possibly due to sample size limitation and post-hoc design of the study. The changes from baseline at week 16 were > 50% higher in the females compared to males for the total daily OFF time (- 1.149 h vs - 0.764 h in males), the total daily ON time (1.283 h vs 0.441 h in males), the UPDRS total score (- 8.300 points vs - 5.253 points in males) and the UPDRS part II score (- 2.574 points vs - 1.016 points in males). The changes from baseline at week 16 were higher in the females compared to males in the "ADL" domain (- 6.965 points vs - 5.772 points in males), the "Emotional well-being" domain (- 6.243 points vs - 4.203 in males), the "Stigma" domain (- 6.185 points vs - 4.913 points in males) and the "Bodily discomfort" domain (- 5.196 points vs 1.099 points in males), while were higher in males in the "Mobility" score (- 6.523 points vs - 4.961 points in females) and the "Communication" score (- 3.863 points vs - 1.564 points in females). Safinamide was shown to improve PD symptoms and quality of life in both male and female Chinese patients. Possible differences in the response between genders need to be further studied in larger and different ethnic populations.