Dopamine agonists and risk of lung cancer in patients with restless legs syndrome

Abstract

Purpose: To examine the association between long-term use of dopamine agonists (DAs) and the risk of lung cancer in patients with restless legs syndrome (RLS).

Methods: We conducted a retrospective cohort study using Optum Clinformatics® database. We included adults ≥40 years diagnosed with RLS during the study period (1/2006-12/2016). Follow-up started with the first RLS diagnosis and ended on the earliest of: incident diagnosis of lung cancer, end of enrollment in the database or end of the study period. The exposure of interest was cumulative duration of DAs use, measured in a time-varying manner. We constructed a multivariable Cox regression model to estimate HRs and 95% CIs for the association between lung cancer and cumulative durations of DA use, adjusting for potential confounding variables.

Results: We identified 295 042 patients with a diagnosis of RLS. The mean age of the cohort was 62.9; 66.6% were women and 82.3% were white. The prevalence of any DA exposure was 40.3%. Compared to the reference group (no use and ≤1 year), the crude HRs for lung cancer were 1.16 (95% CI 0.99-1.36) and 1.14 (95% CI 0.86-1.51) for 1-3 years and >3 years of cumulative DA use, respectively. The adjusted HR for lung cancer was 1.05 (95% CI 0.88-1.25) for 1-3 years and 1.02 (95% CI 0.76-1.37) for >3 years of cumulative DA use, respectively.

Conclusions: At typical doses for the clinical management of RLS, long-term DA use was not associated with risk of lung cancer.

Keywords: RLS; dopamine agonists; epidemiology; lung cancer; time-varying exposure.

Figure 1.

Flow diagram showing inclusion/exclusion criteria applied for study cohort selection.

Figure 2.

Graphical depiction of our study design. On the Y axis, date of cohort entry (day 0); on the X axis, time in days. *Patients were excluded if they had: 1) a diagnosis of Parkinson’s disease, 2) a diagnosis of lung cancer any time prior diagnosis of RLS, 3) < 365 days continuous enrollment, 4) a diagnosis of lung cancer within one year (365 days) of cohort entry. § Baseline conditions were assessed up to 365 days prior cohort entry and included smoking, chronic obstructive pulmonary disease, interstitial pulmonary disease. ** Up to 30-day gap, after cohort entry, were allowed. †Patients were followed from cohort entry to the earliest of outcome of interest (lung cancer), end of the study period or end of enrollment in the database.

Figure 3.

Kaplan-Meier plot^a showing incidence of lung cancer among groups of cumulative to Das * Median time to lung cancer was not estimated because few patients developed lung cancer. Abbreviations: DAs, dopamine agonists.