Marginal Structural Cox Models for Estimating the Association Between β-Interferon Exposure and Disease Progression in a Multiple Sclerosis Cohort

• Published in: American journal of epidemiology Vol. 180; no. 2; pp. 160 - 171
• Main Authors: MOHAMMAD EHSANUL KARIM, GUSTAFSON, Paul, PETKAU, John, YINSHAN ZHAO, SHIRANI, Afsaneh, KINGWELL, Elaine, EVANS, Charity, VAN DER KOP, Mia, OGER, Joel, TREMLETT, Helen
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 15.07.2014
• Subjects: Biological and medical sciences; British Columbia; Cohort Studies; Confounding Factors (Epidemiology); Disease Progression; Epidemiology; General aspects; Humans; Immunologic Factors - therapeutic use; Interferon-beta - therapeutic use; Medical sciences; Medicin och hälsovetenskap; Miscellaneous; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - physiopathology; Neurology; Practice of Epidemiology; Probability; Proportional Hazards Models; Public health. Hygiene; Public health. Hygiene-occupational medicine; Survival Analysis; British Columbia; confounding factors (epidemiology); Multiple sclerosis; Prognosis; marginal structural Cox model; Confounding factor; Epidemiology; Inflammatory disease; bias (epidemiology); Association; epidemiologic methods; survival analysis; Cohort study; Evolution; Methodological bias; Public health; Nervous system diseases; Estimation; Cytokine; Probability; Exposure; Survival; Cox model; Central nervous system disease; Interferon; Structural model; inverse probability weighting; Causality; multiple sclerosis; causality
• ISSN: 0002-9262; 1476-6256; 1476-6256
• DOI: 10.1093/aje/kwu125

Longitudinal observational data are required to assess the association between exposure to β-interferon medications and disease progression among relapsing-remitting multiple sclerosis (MS) patients in the "real-world" clinical practice setting. Marginal structural Cox models (MSCMs) can provide distinct advantages over traditional approaches by allowing adjustment for time-varying confounders such as MS relapses, as well as baseline characteristics, through the use of inverse probability weighting. We assessed the suitability of MSCMs to analyze data from a large cohort of 1,697 relapsing-remitting MS patients in British Columbia, Canada (1995-2008). In the context of this observational study, which spanned more than a decade and involved patients with a chronic yet fluctuating disease, the recently proposed "normalized stabilized" weights were found to be the most appropriate choice of weights. Using this model, no association between β-interferon exposure and the hazard of disability progression was found (hazard ratio = 1.36, 95% confidence interval: 0.95, 1.94). For sensitivity analyses, truncated normalized unstabilized weights were used in additional MSCMs and to construct inverse probability weight-adjusted survival curves; the findings did not change. Additionally, qualitatively similar conclusions from approximation approaches to the weighted Cox model (i.e., MSCM) extend confidence in the findings.