Examining the effects of comorbidities on disease-modifying therapy use in multiple sclerosis

Abstract

Objective: Comorbidities are common in multiple sclerosis (MS) and adversely affect health outcomes. However, the effect of comorbidity on treatment decisions in MS remains unknown. We aimed to examine the effects of comorbidity on initiation of injectable disease-modifying therapies (DMTs) and on the choice of the initial DMT in MS.

Methods: We conducted a retrospective observational analysis using population-based health administrative and linked clinical databases in 3 Canadian provinces. MS cases were defined as any individual with ≥3 diagnostic codes for MS. Cohort entry (index date) was the first recorded demyelinating disease-related claim. The outcomes included choice of initial first-line DMTs and time to initiating a DMT. Logistic and Cox regression models were used to examine the association between comorbidity status and study outcomes, adjusting for sex, age, year of index date, and socioeconomic status. Meta-analysis was used to estimate overall effects across the 3 provinces.

Results: We identified 10,698 persons with incident MS, half of whom had ≥1 comorbidities. As the total number of comorbidities increased, the likelihood of initiating a DMT decreased. Comorbid anxiety and ischemic heart disease were associated with reduced initiation of a DMT. However, patients with depression were 13% more likely to initiate a DMT compared to those without depression at the index date (adjusted hazard ratio 1.13; 95% confidence interval 1.00-1.27).

Conclusions: Comorbidities are associated with treatment decisions regarding DMTs in MS. A better understanding of the effects of comorbidity on effectiveness and safety of DMTs is needed.

Figure 1. Association between number of comorbidities and the likelihood of disease-modifying therapy (DMT) initiation

^aResults were obtained from Cox proportional hazards models with comorbidity count at index date as a time-dependent variable (i.e., count × time). ^bResults were obtained from Cox proportional hazard models with comorbidity count during follow up as a time-varying variable. Models were adjusted for age, sex, year of index date, and socioeconomic status. CI = confidence interval.

Figure 2. Each individual comorbidity at the index date and the hazard ratios (HRs) of subsequent disease-modifying therapy (DMT) initiation^a

^aResults were obtained from time-fixed Cox proportional hazards models. Reference group was patients without each individual comorbidity and comorbidity by the index date. Model was adjusted for age, sex, year of index date, and socioeconomic status. CI = confidence interval.

Figure 3. Total number of comorbidities by the index date and choice of initial disease-modifying therapy received

^aThe comorbidities of interest included diabetes, hypertension, hyperlipidemia, heart disease, chronic lung disease, epilepsy, anxiety, depression, and bipolar disorder. ^bReference groups were patients with no (0) comorbidity by the index date. Models were adjusted for age, sex, year of index date, and socioeconomic status. ^cResults were obtained from logistic regression models. Odds ratios represent the relative odds of receiving glatiramer acetate compared to the odds of receiving interferon-β among those without comorbidities by the index date. CI = confidence interval.