β2-Agonists and the Incidence of Parkinson Disease

Francesco Giorgianni; Pierre Ernst; Sophie Dell'Aniello; Samy Suissa; Christel Renoux

Disclosures

Am J Epidemiol. 2020;189(8):801-810. 

In This Article

Abstract and Introduction

Abstract

A recent study found a decreased risk of Parkinson disease (PD) associated with the β2 adrenergic agonist (β2-agonist) salbutamol. However, other mechanisms might explain this apparent association. Using the UK Clinical Practice Research Datalink, we formed a cohort of 2,430,884 patients aged 50 years or older between 1995 and 2016. During follow-up, 8,604 cases of PD were identified and matched to 86,040 controls on sex, age, date of cohort entry, and duration of follow-up, after applying a 1-year latency time window. Incidence rate ratios of PD associated with use of β2-agonists were estimated using conditional logistic regression. Ever-use of β2-agonists was associated with a 17% decreased rate of PD (rate ratio = 0.83, 95% confidence interval: 0.75, 0.91) compared with no use. However, this association was limited to early short-term use and was no longer observed after more than 2 years of cumulative duration of use (rate ratio = 0.97, 95% confidence interval: 0.80, 1.17). A similar pattern was observed when stratifying by time since first β2-agonist prescription and by duration of follow-up. The apparent association of β2-agonists with a decreased risk of PD is likely the result of reverse causality rather than a biological effect of these drugs on the risk of PD.

Introduction

One of the neuropathological hallmarks of Parkinson disease (PD) is the development of abnormal aggregated α-synuclein, known as Lewy bodies, encoded by the gene SNCA.[1] A recent study identified β2 adrenergic agonists (β2-agonists) as drugs capable of reducing SNCA expression, thus potentially slowing down the formation of Lewy bodies and the development of PD.[2] In a cohort study using the Norwegian administrative health databases, the same authors found a 34% reduction in the incidence of PD associated with salbutamol, the most commonly used β2-agonist in Norway, compared with no use, and a markedly increased risk of PD with use of the β-blocker (β-antagonist) propranolol.[2]

β2-agonists such as salbutamol are already marketed and readily available; therefore, these drugs might represent a unique opportunity for the prevention and treatment of PD. As such, the above findings generated substantial scientific interest, given the lack of neuroprotective drugs in PD. On the other hand, concern has been raised that these findings, if not reliable, might influence physicians' and patients' behavior, leading to unregulated off-label use of β2-agonists to treat PD.[3] Indeed, alternative explanations, in particular reverse causality, might be responsible for these results. Specifically, early signs and symptoms of yet undiagnosed PD, such as tremor, might prompt initiation of some medications such as β-blockers and, conversely, deter physicians from prescribing drugs such as β2-agonists. This phenomenon might lead to spurious associations between these medications and PD. Therefore, we aimed to further explore the putative neuroprotective effect of β2-agonists on the incidence of PD in a large population-based cohort study. As a secondary objective, we also assessed the association between use of β-blockers and the incidence of PD.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....