Non-persistence was defined as discontinuing (at least 60?days without DMT) or switching DMTs. after being newly treated with a DMT from January 2009 through March 2017, with 12?months of continuous enrollment pre- and post-index. Non-persistence was defined as discontinuing (at least 60?days without DMT) or switching DMTs. MS relapses were defined using a validated claims-based algorithm. Multivariable analysis was used to examine odds of 12-month persistence, odds of post-index relapse, and quantity of relapses. Results In total, 4121 patients with MS met all inclusion criteria (mean age 46.4?years; female 76.2%). Overall, 49.6% switched to an oral DMT, 36.5% to an injectable DMT, and 13.9% to an infusion DMT. Switching DMTs resulted in a 32.4% reduction in relapses between pre- and post-index. Only 54.6% of patients were persistent throughout the first year. Patients who switched to oral DMTs experienced 95% higher adjusted odds of persistence and 18% lower adjusted odds of a post-index period relapse than patients who switched to injectable DMTs. The number of baseline relapses was not associated with persistence but with 68% higher odds of a post-index relapse, with each additional baseline relapse associated with a 44% increase in quantity of post-index relapses. Conclusions Among patients with MS who switched DMTs, persistence was consistently low regardless of Hoechst 33258 analog 2 treatment. Although persistence with oral DMTs was slightly higher than with injectable DMTs, overall results show poor persistence to second-line therapy and spotlight the need to improve long-term persistence with DMTs. Electronic supplementary material The online version of this article (10.1007/s12325-020-01367-1) contains supplementary material, which is available to authorized users. value of less than 0.05 was set a priori as the threshold for statistical significance. All analyses were conducted using WPS version 4.1 (World Programming, UK). Results Patient Characteristics Of the 227,893 recognized patients with MS, 25,708 (11.3%) were considered DMT na?ve and, among these, 4121 (16.0%) switched to a second discrete DMT and met the final inclusion criteria. The full patient P4HB selection can be found in Fig.?1. Patients generally switched to an oral (49.6%) or injectable (36.5%) DMT. Of the 13.9% of patients who switched to an infusion, 94% switched to natalizumab. Open in a separate windows Fig.?1 Patient selection. DMT disease-modifying therapy, MS multiple sclerosis The majority of patients who switched were receiving an injectable DMT. Of those who switched (indexed on) to an oral, injectable, or infusion, 80.5%, 82.9%, and 80.6% did so from an injectable (Table?S1 in the supplementary material). Patients generally switched within 5?months after discontinuing their Hoechst 33258 analog 2 first DMT (Table?1), and the mean time from the end of the initial DMT to the switch ranged from 110.3?days for switching to injectable DMTs to 169.6?days for switching to oral DMTs. Table?1 Patient characteristics among patients switching disease-modifying therapies (%)]3140 (76.2)1523 (74.5)1185 (78.7)432 (75.5)Geographic region [(%)]?Northeast759 (18.4)378 (18.5)275 (18.3)106 (18.5)?North central997 (24.2)523 (25.6)369 (24.5)105 (18.4)?South1599 (38.8)771 (37.7)556 (36.9)272 (47.6)?West737 (17.9)355 (17.4)296 (19.7)86 (15.0)?Unknown29 (0.7)16 (0.8)10 (0.7)3 (0.5)Index 12 months [(%)]?2009158 (3.8)0 (0.0)141 (9.4)17 (3.0)?2010298 (7.2)16 (0.8)225 (14.9)57 (10.0)?2011549 (13.3)162 (7.9)289 (19.2)98 (17.1)?2012476 (11.6)123 (6.0)252 (16.7)101 (17.7)?2013917 (22.3)703 (34.4)139 (9.2)75 (13.1)?2014566 (13.7)395 (19.3)119 (7.9)52 (9.1)?2015563 (13.7)310 (15.2)179 (11.9)74 (12.9)?2016491 (11.9)281 (13.8)133 (8.8)77 (13.5)?2017103 (2.5)53 (2.6)29 (1.9)21 (3.7)Days from first DMT to switch,a mean (SD)140.8 (297.9)169.6 (330.5)110.3 (267.0)118.5 (236.6)Comorbid conditions [(%)]?Fatigue1009 (24.5)487 (23.8)362 (24.0)160 (28.0)?Hypertension892 (21.6)450 (22.0)331 (22.0)111 (19.4)?Depression805 (19.5)372 (18.2)298 (19.8)135 (23.6)?Gait troubles647 (15.7)292 (14.3)221 (14.7)134 (23.4)?Hyperlipidemia625 (15.2)323 (15.8)227 (15.1)75 (13.1)Concomitant medications [(%)]?Opioids1711 (41.5)809 (39.6)671 (44.6)231 (40.4)?Antidepressants1646 (39.9)794 (38.9)607 (40.3)245 (42.8)?Antispasmodics1460 (35.4)700 (34.3)508 (33.7)252 (44.1)?Neuropathic pain medications1318 (32.0)631 (30.9)484 (32.1)203 (35.5)?NSAIDs/COX-2 inhibitors1177 (28.6)563 (27.6)437 (29.0)177 (30.9) Hoechst 33258 analog 2 Open in a separate window aFrom end of days supply or clinical benefit of last claim for first DMT until index date cyclooxygenase-2, disease-modifying therapy, nonsteroidal anti-inflammatory drugs Patient demographics were consistent across routes of administration, except for during the index years, which were driven by US Food and Drug Administration approval of specific drugs. Patients who switched DMTs were, on average, 46.4?years of age at the time of the switch (Table?1). The majority of patients were female (76.2%), from a southern geographic region (38.8%), and switched their DMT in 2013 or later (64.1%). Comorbid conditions and concomitant medication use were consistent across all routes of administration and.