Real-world effectiveness of switching treatment after initial platform injectable disease-modifying therapies in pediatric multiple sclerosis in the US
Aaron Abrams1, Michael Waltz2, Theron Casper2, Gregory Aaen3, Leslie Benson4, Leigh Charvet5, Tanuja Chitnis6, Carla Francisco7, Mark Gorman4, Manu Goyal8, Jennifer Graves9, Lauren Krupp5, Timothy Lotze10, Soe Mar8, Mary Rensel1, Moses Rodriguez11, John Rose2, Alice Rutatangwa7, Teri Schreiner12, Nikita Shukla13, Jan-Mendelt Tillema11, Bianca Weinstock-Guttman14, Yolanda Wheeler15, Emmanuelle Waubant7, Kristen Krysko16
1Cleveland Clinic, 2University of Utah, 3Loma Linda University, 4Children's Hospital Boston, 5New York University, 6Brigham and Women's Hospital, 7University of California, San Francisco, 8Washington University at St. Louis, 9University of California, San Diego, 10Texas Children's Hospital, 11Mayo Clinic, 12Children's Hospital Colorado, 13Baylor College of Medicine, 14University At Buffalo, 15University of Alabama at Birmingham, 16St. Michael's Hospital
Objective:
To assess real-world effectiveness of switching DMT on disease activity in pediatric MS/CIS initially treated with platform injectable.
Background:
Treatment of pediatric MS is challenging as most DMTs lack efficacy data, including switching from injectable DMT.
Design/Methods:
This is a cohort study of pediatric MS/CIS at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with platform injectable (interferon-β, glatiramer acetate) and switched to other injectable, oral (dimethyl fumarate, fingolimod, teriflunomide) or infusion (natalizumab, rituximab, ocrelizumab, alemtuzumab) DMT. Relapse rate after switch was modeled with negative binomial regression, adjusted for preidentified confounders (onset age, disease duration, sex, race/ethnicity, BMI, first event severity and localization, annualized relapse rate (ARR), new T2 lesions, new gadolinium-enhancing lesions, EDSS).
Results:
212 children switched DMT before 18 years of age (67% female, 95% MS). Of these, 93 switched from injectable to injectable, 76 injectable to oral and 43 injectable to infusion. Compared to switching to another injectable, oral or infusion switchers were older at onset (injectable 12.3 years vs oral 13.5, infusion 14.2) and at switch date (injectable 14.6 years vs oral 16, infusion 15.7). Infusion switchers were more likely to have new enhancing lesions prior to switch (injectable 45% vs oral 28%, infusion 67%). In adjusted analysis, compared to switchers from injectable to injectable (ARR 0.59, 95%CI 0.28-1.26), ARR was lower for injectable to oral (ARR 0.22, 95%CI 0.10-0.48; rate ratio 0.38, 95%CI 0.21-0.69) and injectable to infusion (ARR 0.15, 95%CI 0.06-0.35; rate ratio 0.25, 95%CI 0.11-0.53) (p < 0.001). The adjusted NNT to prevent 1 relapse with oral over injectable was 2.70 and infusion over injectable was 2.22.
Conclusions:
Switching from platform injectable to oral or infusion vs another injectable DMT led to better disease activity control of pediatric MS. Long-term safety data for oral and infusion DMTs are required.