Sex differences by design and outcome in the Safety of Urate Elevation in PD (SURE-PD) trial

OBJECTIVETo investigate whether women and men with Parkinson disease (PD) differ in their biochemical and clinical responses to long-term treatment with inosine. METHODSThe Safety of Urate Elevation in Parkinson’s Disease (SURE-PD) trial enrolled 75 people with early PD and baseline serum urate below 6 mg/dL and randomized them to 3 double-blinded treatment armsoral placebo or inosine titrated to produce mild (6.1–7.0 mg/dL) or moderate (7.1–8.0 mg/dL) serum urate elevation for up to 2 years. Parkinsonism, serum urate, and plasma antioxidant capacity were measured at baseline and repeatedly on treatment; CSF urate was assessed once, at 3 months. Here in secondary analyses results are stratified by sex. RESULTSInosine produced an absolute increase in average serum urate from baseline that was 50% greater in women (3.0 mg/dL) than in men (2.0 mg/dL), consistent with expected lower baseline levels in women. Similarly, only among women was CSF urate significantly greater on mild or moderate inosine (+87% [p < 0.001] and +98% [p < 0.001], respectively) than on placebo (in contrast to men+10% [p = 0.6] and +14% [p = 0.4], respectively). Women in the higher inosine dosing group showed a 7.0 Unified Parkinson’s Disease Rating Scale (UPDRS) points/year lower rate of decline vs placebo (p = 0.01). In women, slower rates of UPDRS change were associated with greater increases in serum urate (r = −0.52; p = 0.001), and with greater increases in plasma antioxidant capacity (r = −0.44; p = 0.006). No significant associations were observed in men. CONCLUSIONSInosine produced greater increases in serum and CSF urate in women compared to men in the SURE-PD trial, consistent with the studyʼs design and with preliminary evidence for slower clinical decline in early PD among women treated with urate-elevating doses of inosine. CLINICALTRIALS.GOV IDENTIFIERNCT00833690. CLASSIFICATION OF EVIDENCEThis study provides Class II evidence that inosine produced greater urate elevation in women than men and may slow PD progression in women.