Amber Salter1, Kaarina Kowalec2, Kathryn C Fitzgerald2, Gary Cutter2, Ruth Ann Marrie2. 1. From the Department of Biostatistics (A.S.), Washington University in St. Louis, MO; College of Pharmacy (K.K.), and Departments of Internal Medicine and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institutet, Solna, Sweden; Department of Neurology (K.C.F.), Johns Hopkins School of Medicine, Baltimore, MD; and Department of Biostatistics (G.C.), University of Alabama in Birmingham School of Public Health. amber@wustl.edu. 2. From the Department of Biostatistics (A.S.), Washington University in St. Louis, MO; College of Pharmacy (K.K.), and Departments of Internal Medicine and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institutet, Solna, Sweden; Department of Neurology (K.C.F.), Johns Hopkins School of Medicine, Baltimore, MD; and Department of Biostatistics (G.C.), University of Alabama in Birmingham School of Public Health.
Abstract
OBJECTIVE: To determine whether comorbidity is associated with clinical (relapses, disability worsening) and MRI outcomes in multiple sclerosis (MS) by conducting a secondary analysis of the CombiRx clinical trial. METHODS: CombiRx compared interferon beta-1a, glatiramer acetate, and the combination of these agents. For participants eligible for evaluation of 6-month confirmed disability worsening, we used medical history, concomitant medications, and adverse events to ascertain comorbidity status. Comorbid conditions evaluated included hypertension, dyslipidemia, diabetes mellitus, depression, anxiety disorders, and migraine. Clinical outcomes included disease activity consisting of protocol-defined relapses, disability worsening, and MRI activity. We summarized the prevalence of these comorbid conditions and their association with disease activity and its components using multivariable Cox regression. RESULTS: Of the 1,008 participants randomized, 959 (95.1%) were eligible for assessment of 6-month disability worsening; for this subgroup, the median length of follow-up was 3.4 years (range 0.5-6.9 years). Overall, 55.1% of participants had ≥1 comorbidity at enrollment. After adjustment, anxiety (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.01-1.55) and dyslipidemia (HR 1.32, 95% CI 1.01-1.72) were associated with an increased hazard of any disease activity, while migraine (HR 0.80, 95% CI 0.67-0.97) was associated with a decreased hazard. CONCLUSIONS: In this large trial population with rigorously obtained outcomes, comorbid conditions were common among participants and influenced disease outcomes, including relapses. The comorbidity burden of clinical trial participants with MS may be an important factor in the outcome of clinical trials. Additional investigations of the impact of comorbidity on clinical trial outcomes and response to disease-modifying therapies are warranted.
RCT Entities:
OBJECTIVE: To determine whether comorbidity is associated with clinical (relapses, disability worsening) and MRI outcomes in multiple sclerosis (MS) by conducting a secondary analysis of the CombiRx clinical trial. METHODS: CombiRx compared interferon beta-1a, glatiramer acetate, and the combination of these agents. For participants eligible for evaluation of 6-month confirmed disability worsening, we used medical history, concomitant medications, and adverse events to ascertain comorbidity status. Comorbid conditions evaluated included hypertension, dyslipidemia, diabetes mellitus, depression, anxiety disorders, and migraine. Clinical outcomes included disease activity consisting of protocol-defined relapses, disability worsening, and MRI activity. We summarized the prevalence of these comorbid conditions and their association with disease activity and its components using multivariable Cox regression. RESULTS: Of the 1,008 participants randomized, 959 (95.1%) were eligible for assessment of 6-month disability worsening; for this subgroup, the median length of follow-up was 3.4 years (range 0.5-6.9 years). Overall, 55.1% of participants had ≥1 comorbidity at enrollment. After adjustment, anxiety (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.01-1.55) and dyslipidemia (HR 1.32, 95% CI 1.01-1.72) were associated with an increased hazard of any disease activity, while migraine (HR 0.80, 95% CI 0.67-0.97) was associated with a decreased hazard. CONCLUSIONS: In this large trial population with rigorously obtained outcomes, comorbid conditions were common among participants and influenced disease outcomes, including relapses. The comorbidity burden of clinical trial participants with MS may be an important factor in the outcome of clinical trials. Additional investigations of the impact of comorbidity on clinical trial outcomes and response to disease-modifying therapies are warranted.
Authors: Ruth Ann Marrie; Ronak Patel; Chase R Figley; Jennifer Kornelsen; James M Bolton; Lesley A Graff; Erin L Mazerolle; Carl Helmick; Md Nasir Uddin; Teresa D Figley; James J Marriott; Charles N Bernstein; John D Fisk Journal: Front Neurol Date: 2022-05-24 Impact factor: 4.086