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Discontinuation of Disease-Modifying Therapy in Patients With Multiple Sclerosis Over Age 60 Multiple Sclerosis

" …the current study supports the option of DMT discontinuation in older

Take-home message • There are no guidelines for discontinuation of disease-modifying therapy (DMT) in multiple sclerosis patients. This retrospective observational study reviewed cases at three American multiple sclerosis centers to characterize anyone over the age of 60 who discontinued DMT. Of 600 patients identified, 178 discontinued DMT at the average age of 65, 68% discontinuations being provider initiated due to side effects (49%), stable disease (28%), age (22.5%), lack of benefit (21%), and secondary progressive disease (20%), comorbidities (15%), and cost (10%). In patients who re-initiated DMT (n=19; 10.7%) the reasons were patient preference (n=8), MRI changes (n=3), clinical progression (n=4), entering a trial (n=1), and provider preference (n=3). There was one relapse documented in those who discontinued DMT. Although studies of younger patients discontinuing DMT show increases in relapses and disease progression, these increases were not observed in the older patients in this study. • Age should be a factor when considering discontinuation of DMT in patients with multiple sclerosis. Shila Azodi MD O ver the past 20 years, unprecedented advances have been made in the treat- ment of multiple sclerosis (MS). As of April 2018, 15 disease-modifying therapies (DMT) have received regulatory approval for the management of relapsing MS. The majority of these therapeutic agents were designed to reduce the development of MS inflammatory lesions and associated clinical exacerbations by modulating path- ogenic immune cells in the periphery. However, it is unclear when, if ever, DMT should be discontinued in patients following years of disease quiescence and/or following transition into a secondary progressive stage (during which gradual disability accumu- lation occurs independent of new gadolinium-enhancing lesions and/or relapses). This issue is particularly pertinent to MS patients in late middle age or older because the frequency of enhancing lesions and clinical relapses naturally declines over time and several of the approved DMTs were found to be ineffective in progressive MS trials. The current manuscript describes a retrospective, observational “real-world” study of DMT discontinuation in MS patients over 60 years of age who had been treated with DMT for at least 2 years. Of the 600 individuals included, 178 (29.7%) discontinued DMT. There was only 1 clinical relapse among the discontinuers, the vast majority of whom remained off DMT. The reinitiation rate was approximately 10% and primarily driven by patient preference as opposed to MRI changes or clinical progression. Although more definitive data on this topic will await the outcome of an ongoing prospective rand- omized controlled trial, the current study supports the option of DMT discontinuation in older MS patients with a stable or progressive clinical course and no recent evidence of neuroinflammatory activity. COMMENT By Benjamin Segal MD

Abstract BACKGROUND The risk-benefit ratio of continuing immunomodulating disease-modifying therapy (DMT) in older multiple sclerosis (MS) patients is unknown. OBJECTIVE To evaluate clinical and patient-re- ported outcomes after stopping DMT in older MS patients. METHODS Retrospective, observational study identifying patients from our MS clinics who were aged over 60 and on DMT > 2 years. Cause-specific Cox proportional hazards regres- sion modeled time to discontinuation and time to reinitiation of therapy. Pre- and post-discon- tinuation comparisons of Performance Scales (PS), Timed 25-Foot Walk, and Patient Health Questionnaire-9 (PHQ9) were analyzed using linear mixed models. RESULTS A total of 600 patients were included, with 178 (29.7%) discontinuing. Discontinuers were 2.2years older, had 3.2years longer dis- ease duration, and 1.6 years lesser treatment exposure. Providers initiated discontinuation more than patients (68.0%). Only one clinical relapse occurred in discontinuers. A proportion (10.7%) reinitiated DMT. Provider-initiated discon- tinuers restarted less often (hazard ratio (HR): 0.34; 95% confidence interval (CI): 0.12-0.9). In discontinuers, relapsing-remitting patients had lower PS on average than primary progres- sive. Provider-initiated discontinuation was associated with lower PS than patient- initiated discontinuation. PHQ9 scores appeared higher in those stopping intravenous (IV) therapies than interferons. Lower PS and PHQ9 indicate bet- ter outcomes. CONCLUSION Most patients over age 60, who dis- continued DMT, remained off DMT. This study provides real-world data that may guide clini- cians considering discontinuing DMT. Discontinuation of Disease-Modifying Therapy in Patients With Multiple Sclerosis Over Age 60. Mult Scler 2018 Mar 20;[EPub Ahead of Print], LH Hua, TH Fan, D Conway, et al. www.practiceupdate.com/c/65862 MS patients with a stable or progressive clinical course and no recent evidence of neuroinflammatory activity. "

Dr. Segal is Holtom-Garrett Professor of Neurology and Director of the Multiple Sclerosis Center at the University of Michigan Medical School in Ann Arbor, Michigan.

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