Changes in patient-reported outcomes between continuers and discontinuers of disease modifying therapy in patients with multiple sclerosis over age 60

Abstract

Background: The risk benefit ratio of continuing immunomodulating disease modifying therapy (DMT) in older MS patients is unknown. To date, only retrospective observational studies on DMT discontinuation have been published. In these studies, DMT discontinuation was based solely on disease stability and patients frequently had to restart treatment. Our prior study demonstrated that discontinuing DMT can be more successful when age is also considered. The impact of discontinuing DMT on patients' quality of life has not been previously explored. The objective of this study is to determine changes in outcomes over time between those who continued versus discontinued DMT using patient-reported outcomes (European Quality of Life 5 Dimensions (EQ-5D) index, Performance Scales (PS), and Patient Health Questionnaire (PHQ9)) and walking speed (Timed 25-foot walk) in MS patients over age 60.

Methods: We conducted a retrospective, observational study in which we identified patients from our MS clinics who were 60 years of age or older and had been on DMT ≥2 years. We compared outcome evolution over time among treatment groups (continuers, discontinuers before discontinuation (DBD), and discontinuers after discontinuation (DAD)), by creating separate mixed-effects linear regression models that included an interaction term between time from age 60 and treatment group to study outcome trajectories. Independent variables were time from age 60 and treatment group, with the following covariates: age at diagnosis, gender, disease course at MS diagnosis, time on DMT, baseline DMT, and ambulation status at age 60.

Results: 178 of 600 patients discontinued DMT, and 89.3% (n = 159) of those who discontinued remained off DMT. Only the EQ-5D mixed-effects linear regression model with the interaction term was statistically significant (omnibus p-value = 0.043). The slope relating time to EQ-5D was significantly different when comparing continuers to DBD (0.009, 95% CI 0.002-0.016, p-value = 0.015). The slopes were not significantly different when comparing continuers to DAD, or when comparing the before and after discontinuation slopes among the discontinuers. With the interaction term removed, there were no significant differences between the three groups for any other outcome.

Conclusion: Most patients over age 60 who discontinued DMT remained off treatment. Among the outcomes, only EQ-5D demonstrated significant differences over time, with continuers having lower quality of life scores compared to DBD. There were no significant group differences in PS, T25FW and PHQ-9. Overall, stopping DMT appears to have minimal effect on outcomes over the study period in patients over age 60.

Keywords: Discontinuing therapy; Disease modifying therapy; Long term management; Multiple sclerosis; Patient reported outcome measures.