Effect of leukotriene receptor antagonist use on the future risk of Parkinson's disease in older patients with asthma.

Abstract

Current treatments for Parkinson's disease focus on symptom management, with no therapies yet demonstrated to slow disease progression. Leukotriene receptor antagonists, widely used for asthma, have shown potential neuroprotective effects for Parkinson's disease in preclinical studies, but have also been associated with an elevated risk of neuropsychiatric events and sleep disorders. We assessed the effect of leukotriene receptor antagonist treatment on the risk of Parkinson's disease, neuropsychiatric events, and sleep disorders in patients with asthma aged over 50 years. We conducted a cohort study using the UK Clinical Practice Research Datalink between January 2000 and December 2020. The study emulated sequential target trials (n = 140) using observational data, comparing leukotriene receptor antagonist treatment to no leukotriene receptor antagonist treatment among patients aged 50-84 years with asthma. The primary outcome was the risk of incident Parkinson's disease, and the secondary outcomes were neuropsychiatric events (anxiety, depression, and psychosis), and sleep disorders. Propensity score matching was employed to minimize confounding. We used pooled logistic regression models to calculate risk ratios as observational analogues of intention-to-treat and per protocol effects. A total of 97 049 matched pairs were included in the analysis, with 573 Parkinson's disease cases observed in the leukotriene receptor antagonist group and 537 in the nonleukotriene receptor antagonist group over a median follow-up of 5.9 years and 5.7 years, respectively. No significant difference in Parkinson's disease risk was observed between the two groups in either the intention-to-treat analysis [10-year risk ratio: 1.09; 95% confidence interval (CI), 0.94-1.26] or the per protocol analysis (10-year risk ratio: 0.95; 95% CI, 0.75-1.16). However, there was a higher risk of depression (intention-to-treat effect: 10-year risk ratio: 1.12; 95% CI, 1.07-1.16; number-needed-to-harm = 93; per protocol effect: 10-year risk ratio: 1.15; 95% CI, 1.08-1.22; number-needed-to-harm = 75) and sleep disorders (intention-to-treat effect: 10-year risk ratio: 1.14; 95% CI, 1.11-1.19; number-needed-to-harm = 77; per protocol effect: 10-year risk ratio: 1.12; 95% CI, 1.06-1.19; number-needed-to-harm = 88) with leukotriene receptor antagonist treatment. No clear effect was observed for anxiety or psychosis. Leukotriene receptor antagonist treatment was not associated with an altered risk of Parkinson's disease among people aged 50-84 years with asthma but was linked to a higher incidence of neuropsychiatric events.