Kristen M Krysko1, Jennifer S Graves1,2, Mary Rensel3, Bianca Weinstock-Guttman4, Alice Rutatangwa1, Gregory Aaen5, Anita Belman6, Leslie Benson7, Tanuja Chitnis8, Mark Gorman7, Manu S Goyal9, Yolanda Harris10, Lauren Krupp6, Timothy Lotze11, Soe Mar12, Manikum Moodley13, Jayne Ness14, Moses Rodriguez15, John Rose16, Teri Schreiner17, Jan-Mendelt Tillema15, Michael Waltz18, T Charles Casper18, Emmanuelle Waubant1. 1. UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA. 2. Department of Neurology, University of California, San Diego, La Jolla, CA. 3. Department of Neurology, Cleveland Clinic, Cleveland, OH. 4. Department of Neurology, State University of New York at Buffalo, Buffalo, NY. 5. Department of Pediatrics, Loma Linda University, San Bernardino, CA. 6. Department of Neurology, New York University Langone Medical Center, New York, NY. 7. Department of Neurology, Boston Children's Hospital, Boston, MA. 8. Department of Pediatric Neurology, Massachusetts General Hospital, Boston, MA. 9. Mallinckrodt Institute of Radiology, Washington University in Saint Louis, St Louis, MO. 10. Department of Nursing, University of Alabama at Birmingham, Birmingham, AL. 11. Department of Neurology, Texas Children's Hospital, Houston, TX. 12. Department of Neurology, Washington University in Saint Louis, St Louis, MO. 13. Department of Pediatrics and Neurology, Dell Children's Hospital, University of Texas, Austin, TX. 14. Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL. 15. Department of Neurology, Mayo Clinic, Rochester, MN. 16. Department of Neurology, University of Utah, Salt Lake City, UT. 17. Departments of Neurology and Pediatrics, University of Colorado, Aurora, CO. 18. Department of Pediatrics, University of Utah, Salt Lake City, UT.
Abstract
OBJECTIVE: To assess real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (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-β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders. 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 brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS-quintile. RESULTS: A total of 741 children 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. In PS-quintile-adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (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 rather than injectable DMTs for 3.7 person-years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [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. INTERPRETATION: 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 are required. ANN NEUROL 2020 ANN NEUROL 2020;88:42-55.
OBJECTIVE: To assess real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (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-β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders. 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 brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS-quintile. RESULTS: A total of 741 children 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. In PS-quintile-adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (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 rather than injectable DMTs for 3.7 person-years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [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. INTERPRETATION: 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 are required. ANN NEUROL 2020 ANN NEUROL 2020;88:42-55.
Authors: Jennifer H Yang; Torge Rempe; Natalie Whitmire; Anastasie Dunn-Pirio; Jennifer S Graves Journal: Front Neurol Date: 2022-06-03 Impact factor: 4.086
Authors: Aphra Luchesa Smith; Christina Benetou; Hayley Bullock; Adam Kuczynski; Sarah Rudebeck; Katie Hanson; Sarah Crichton; Kshitij Mankad; Ata Siddiqui; Susan Byrne; Ming Lim; Cheryl Hemingway Journal: Children (Basel) Date: 2020-11-09