Association Between Exposure of Ipratropium and Salmeterol and Diagnosis of Multiple Sclerosis: A Matched Case-control Study

Abstract

Purpose: Ipratropium and salmeterol were found to stimulate oligodendrocyte differentiation in a high-throughput drug screening assay; thus, they may play a role in the risk reduction of multiple sclerosis (MS). So far, they have not been examined in any clinical data. This study aims at investigating the association between ipratropium and salmeterol and reduced diagnosis of MS with the use of real-world clinical data.

Methods: We conducted a 1:10 matched case-control study that compared the exposure of ipratropium and salmeterol between patients with MS and control patients over the past 2 years, using the MS Flowsheet Registry of OSF HealthCare Saint Francis Medical Center. Cases were matched to control patients, based on service year/quarter, age, sex, race, and payer type. The relationship was examined with a Poisson regression model and a generalized structural equation model.

Findings: The sample in our analysis included 217 patients with MS and 2164 matched control patients. The mean (SD) age for both patients with MS and control patients was 41 (11.8) years with a range of 18 to 75 years. The MS group had consistently less prescriptions of ipratropium and salmeterol than the control group in the past 1, 2, and 3 years before the index date. Our multivariable analysis found that the control group had 3.2 more prescriptions (95% CI, 1.4-7.1; P = 0.006) of either ipratropium or salmeterol in the past 2 years than the MS group, even if controlling for other confounders. In the generalized structural equation model, we found that use of ipratropium and salmeterol was significantly associated with reduced diagnosis of MS (P = 0.036), whereas smokers and people with family history of MS were more likely to have a diagnosis of MS (P < 0.001).

Implications: The observed association between ipratropium and salmeterol use and reduced diagnosis of MS indicates that they might potentially serve as agents in the treatment of MS.

Keywords: association; case–control study; ipratropium; multiple sclerosis; remyelination; salmeterol.