RESEARCH PAPER Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study Ilya Kister, 1 Tim Spelman, 2,3 Raed Alroughani, 4 Jeannette Lechner-Scott, 5 Pierre Duquette, 6 Francois Grand’Maison, 7 Mark Slee, 8 Alessandra Lugaresi, 9 Michael Barnett, 10 Pierre Grammond, 11 Gerardo Iuliano, 12 Raymond Hupperts, 13 Eugenio Pucci, 14 Maria Trojano, 15 Helmut Butzkueven, 2,3 on behalf of the MSBase Study Group For numbered affiliations see end of article. Correspondence to Dr Ilya Kister, Department of Neurology, NYU Multiple Sclerosis Care Center, NYU School of Medicine, 240 East 38th St, New York, NY 10026, USA; ilya.kister@nyumc.org Authors IK and TS contributed equally to this work. Received 12 April 2016 Revised 18 May 2016 Accepted 23 May 2016 Published Online First 13 June 2016 To cite: Kister I, Spelman T, Alroughani R, et al. J Neurol Neurosurg Psychiatry 2016;87:1133–1137. ABSTRACT Background Discontinuation of injectable disease- modifying therapy (DMT) for multiple sclerosis (MS) after a long period of relapse freedom is frequently considered, but data on post-cessation disease course are lacking. Objectives (1) To compare time to first relapse and disability progression among ‘DMT stoppers’ and propensity-score matched ‘DMT stayers’ in the MSBase Registry; (2) To identify predictors of time to first relapse and disability progression in DMT stoppers. Methods Inclusion criteria for DMT stoppers were: age ≥18 years; no relapses for ≥5 years at DMT discontinuation; follow-up for ≥3 years after stopping DMT; not restarting DMT for ≥3 months after discontinuation. DMT stayers were required to have no relapses for ≥5 years at baseline, and were propensity- score matched to stoppers for age, sex, disability (Expanded Disability Status Score), disease duration and time on treatment. Relapse and disability progression events in matched stoppers and stayers were compared using a marginal Cox model. Predictors of first relapse and disability progression among DMT stoppers were investigated using a Cox proportional hazards model. Results Time to first relapse among 485 DMT stoppers and 854 stayers was similar (adjusted HR, aHR=1.07, 95% CI 0.84 to 1.37; p=0.584), while time to confirmed disability progression was significantly shorter among DMT stoppers than stayers (aHR=1.47, 95% CI 1.18 to 1.84, p=0.001). The difference in hazards of progression was due mainly to patients who had not experienced disability progression in the prebaseline treatment period. Conclusions Patients with MS who discontinued injectable DMT after a long period of relapse freedom had a similar relapse rate as propensity score-matched patients who continued on DMT, but higher hazard for disability progression. INTRODUCTION The therapeutic effect of starting injectable disease- modifying therapies (DMTs)—Interferon β and Glatiramer Acetate—on multiple sclerosis (MS) has been investigated extensively, 1 but little is known about the effect of stopping these drugs. 2 Discontinuing Interferon β (IFNβ) in patients with ongoing relapses leads to disease reactivation to pretreatment levels, 3–5 but could injectable DMTs be safely stopped after a prolonged period of relapse freedom? A definitive answer to this ques- tion requires an adequately powered clinical trial in which some patients are randomised to continue treatment and others—to placebo. 6 Such trials have been successfully carried out in oncology 7 8 and other areas of medicine, but not in MS. In the absence of a randomised discontinuation trial, clini- cians can take recourse in observational studies that utilise a propensity score-matching technique. 9 Such an approach has been used in the MS field to assess long-term treatment effect of IFNβ therapy; 10 impact of IFNβ-neutralising anti- bodies; 11 and effectiveness of therapy switches. 12 In the present work, we make use of propensity score-matching to address the question of whether the clinical course among patients with MS who stopped injectable DMT after being relapse-free over the prior 5 years (‘stoppers’) differs from that of patients who continued on injectable DMT (‘stayers’). We also identify predictors of relapses and disability progression among DMT stoppers. MATERIALS AND METHODS The MSBase Registry The MSBase Registry is a global collaborative research group that prospectively collects outcomes data from MS treatment centres, using an internet- based, physician owned and operated system (http://www.msbase.org). 13 Each centre enters patient data in the offline iMed local electronic database during routine clinic visits and intermit- tently uploads anonymised data sets to the MSBase server. Physicians record clinical information such as date of MS onset, diagnostic criteria used, Expanded Disability Status Score (EDSS) and relapse characteristics. Records are classified as complete and eligible for analyses if they meet a minimum required set of data. Informed consent from all patients according to local laws is required for participation in MSBase and the project holds Human Research Ethics Committee approval or exemption at each contributing centre. Kister I, et al. J Neurol Neurosurg Psychiatry 2016;87:1133–1137. doi:10.1136/jnnp-2016-313760 1133 Multiple sclerosis group.bmj.com on October 26, 2016 - Published by http://jnnp.bmj.com/ Downloaded from