Marginal structural model to evaluate the association between cumulative osteoporosis medication and infection using claims data

SUMMARY: Due to the suboptimal persistence to osteoporosis (OP) treatment, factors triggering treatment discontinuation/switching may be causing time-varying confounding. BP treatment was associated with the risk of overall infection in opposite directions in the unweighted Cox model versus the weighted MSM. The discrepancy of effect estimates for overall infection in the MSM suggested there may be time-varying confounding. INTRODUCTION: Due to the suboptimal persistence to osteoporosis (OP) treatment, factors triggering treatment discontinuation/switching may be affected by prior treatment and confound the subsequent treatment effect, causing time-varying confounding. METHODS: In a US insurance database, the association between joint treatment of bisphosphonates (BP) and other OP medication and the incidence of infections among postmenopausal women was assessed using a marginal structural model (MSM). Stabilized weights were estimated by modeling treatment and censoring processes conditioning on past treatment, and baseline and time-varying covariates. RESULTS: BP treatment was associated with the risk of overall infection in opposite directions in the unweighted Cox model {incidence rate ratio [IRR] [95% confidence interval (CI)] = 1.15 [1.14–1.17]} versus the weighted MSM [IRR (95% CI) = 0.79 (0.77–0.81)], but was consistently associated with a lower risk of serious infection in both the unweighted Cox model [IRR (95% CI] = 0.79 (0.78–0.81)) and the weighted MSM [IRR (95% CI) = 0.71 (0.68–0.75)]. Similar results were found when current and past treatments were simultaneously assessed. CONCLUSIONS: The discrepancy of effect estimates for overall but not serious infection comparing unweighted models and MSM suggested analyses of composite outcomes with a wide range of disease severity may be more susceptible to time-varying confounding. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00198-017-4129-6) contains supplementary material, which is available to authorized users.