Exploring Demographic, Geographical, and Clinical Factors Associated with Persistence to High-Efficacy Therapies in Multiple Sclerosis

Abstract

Background: High-efficacy disease-modifying therapies (DMTs) in multiple sclerosis (MS) are defined as those that reduce relapses by 50%. A majority of these high-efficacy DMTs are administered intravenously at varying intervals, including alemtuzumab every 365 days, mitoxantrone every 90 days, natalizumab every 28 days, ocrelizumab every 182 days, and ublituximab every 168 days. While several studies have investigated the rates of persistence on these high-efficacy DMTs, no studies to date have investigated patient factors associated with the persistence of these high-efficacy infusion DMTs.Objective: To identify demographic, geographical, and clinical factors associated with the persistence of high-efficacy infusion DMTs in MS after 12 months from initiation. Methods: We conducted a retrospective cohort study using the Merative™ Marketscan® Commercial Database. We identified patients diagnosed with MS starting high-efficacy infusion DMTs between January 1, 2018, and December 31, 2020. Persistence was defined as having no evidence of switching to a new therapy or having no gap greater than 60 days beyond the recommended dosing regimens. For each DMT, we used an adjusted multivariable logistic regression model to assess the association between the binary outcome of persistence for 12 months and age, sex, level of rurality, region, health plan type, employment classification, Charlson Comorbidity Index score, mental health comorbidity status, length of MS diagnosis, and presence of a recent MS relapse event. We ran additional scenario analyses to compare the probability of persistence using varying persistence definitions found in the literature. Results: We found that a higher proportion of patients were persistent at 12 months on ocrelizumab (80.9%) versus natalizumab (66.3%). Among patients who survived and were persistent for 12 months, a higher proportion of patients were persistent at 24 months on natalizumab (57.5%) versus alemtuzumab (39.8%) or ocrelizumab (49.8%). Age, sex, region, health plan type, employment classification, mental health comorbidity status, and presence of a recent MS relapse event were not significantly associated with persistence to natalizumab or ocrelizumab at 12 months. We found that the odds of persistence on ocrelizumab were significantly higher in patients living in rural areas versus those living in urban areas (OR: 0.73, 95% CI: 0.54-0.98, p-value: 0.039) and in patients who had been recently diagnosed with MS before starting an infusion DMT (OR: 1.39, 95% CI: 1.05-1.83, p-value: 0.020). The odds of persistence on natalizumab were significantly higher in patients with fewer than two comorbidities (OR: 0.58, 95% CI: 0.35-0.96, p-value: 0.041) and in patients who had been recently diagnosed with MS before starting an infusion DMT (OR: 2.24, 95% CI: 1.68-2.98, p-value<0.001). Conclusion: At 12 months post-index, ocrelizumab was found to have a higher probability of persistence compared to natalizumab, which may be explained by its extended dosing regimen of 182 days versus 28 days. In patients taking ocrelizumab, higher persistence was significantly associated with those living in rural areas compared to urban areas and those who had been recently diagnosed with MS before starting an infusion DMT. In patients on natalizumab, higher persistence was significantly associated with those with fewer than two comorbidities and patients who had been diagnosed with MS within six months before DMT initiation. Future research could explore persistence trends among newer high-efficacy DMTs, including ofatumumab and ublituximab.