Thursday, March 12, 2020

Initial treatment with newer versus injectable disease-modifying therapies In pediatric multiple sclerosis

P066 - Real-world Effectiveness Of Initial Treatment With Newer Versus Injectable Disease-modifying Therapies In Pediatric Multiple Sclerosis
Author Block: K. M. Krysko1, J. S. Graves2, M. Rensel3, B. Weinstock-Guttman4, A. Rutatangwa1, G. Aaen5, B. Anita6, L. Benson7, T. Chitnis8, M. Gorman7, M. S. Goyal9, Y. Harris10, L. Krupp6, T. Lotze11, S. Mar12, M. Moodley3, J. Ness13, M. Rodriguez14, J. Rose15, T. Schreiner16, J. Tillema14, M. Waltz17, T. Casper17, E. Waubant1; 1Department of Neurology, University of California San Francisco, San Francisco, CA, 2Department of Neurology, University of California San Diego, La Jolla, CA, 3Department of Neurology, Cleveland Clinic, Cleveland, OH, 4Department of Neurology, State University of New York at Buffalo, Buffalo, NY, 5Department of Pediatrics, Loma Linda University, San Bernardino, CA, 6Department of Neurology, New York University Langone Medical Center, New York, NY, 7Department of Neurology, Boston Children’s Hospital, Boston, MA, 8Department of Pediatric Neurology, Massachusetts General Hospital, Boston, MA, 9Mallinckrodt Institute of Radiology, Washington University in Saint Louis, St. Louis, MO, 10Department of Nursing, University of Alabama at Birmingham, Birmingham, AL, 11Department of Neurology, Texas Children’s Hospital, Houston, TX, 12Department of Neurology, Washington University in Saint Louis, St. Louis, MO, 13Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 14Department of Neurology, Mayo Clinic, Rochester, MN, 15Department of Neurology, University of Utah, Salt Lake City, UT, 16Departments of Neurology & Pediatrics, University of Colorado, Aurora, CO, 17Department of Pediatrics, University of Utah, Salt Lake City, UT.

Background: Treatment of pediatric multiple sclerosis (MS) is challenging as most disease-modifying therapies (DMT) lack randomized controlled trial data in children.

Objectives: We assessed real-world effectiveness of initial treatment with newer compared to injectable DMTs on disease activity in pediatric MS and clinically isolated syndrome (CIS).

Methods: This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon-beta or glatiramer acetate) DMTs. Propensity scores (PS) were computed with logistic regression to predict newer DMT use, including pre-identified confounders (sex, race, ethnicity, site, age at onset and first DMT, first event characteristics, height, weight, diagnosis, number of relapses in prior 6 months, new T2 hyperintense or gadolinium enhancing lesions in prior 6 months, baseline EDSS). Relapse rate while on initial DMT was modeled with negative binomial regression, adjusted for PS-quintile. Time to new/enlarging T2 hyperintense and gadolinium-enhancing lesions on MRI brain were modeled with midpoint survival analyses, adjusted for PS-quintile.

Results: 741 children (66% female, 15% CIS) began therapy before 18 years, 197 with newer and 544 with injectable DMTs. Those started on newer DMTs were older (15.2 vs. injectable 14.4 years, p=0.001) and less likely to have a monofocal presentation (37% vs. injectable 55%, p<0.001). Number of relapses in the prior 6 months was slightly lower in those started on newer DMT (0.8 vs. injectable 1.0), while first event severity and EDSS were similar between groups. Balance in confounders was acceptable within PS-quintiles. In PS-quintile adjusted analysis, those started on newer DMTs had lower relapse rate than those on injectables (rate ratio 0.45, 95% CI 0.29-0.70, p<0.001; rate difference 0.27, 95% CI 0.14-0.40, p=0.004). One would need to treat with newer over injectable DMTs for 3.7 person-years to prevent one relapse. Those started on newer DMTs also had lower rate of new/enlarging T2 (HR 0.51, 95% CI 0.36-0.72, p<0.001) and gadolinium-enhancing lesions (HR 0.38, 95% CI 0.23-0.63, p<0.001) than those on injectables.

Conclusions: Initial treatment of pediatric MS/CIS with newer DMTs led to better disease activity control compared to injectables, supporting greater effectiveness of newer therapies. Long-term safety data for newer DMTs is required.

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