Real-world effectiveness of initial treatment with newer versus injectable disease-modifying therapies in pediatric multiple sclerosis in the US
ECTRIMS Online Library. Krysko K. 09/12/19; 279526; 249
Kristen M Krysko
Kristen M Krysko
Contributions
Abstract

Abstract: 249

Type: Free Communications

Abstract Category: Clinical aspects of MS - Paediatric MS

K.M. Krysko1, J.S. Graves1,2, M. Rensel3, B. Weinstock-Guttman4, A. Rutatangwa1, G. Aaen5, L. Benson6, T. Chitnis7, M. Gorman6, M. Goyal8, Y. Harris9, L. Krupp10, T. Lotze11, S. Mar8, M. Moodley3, M. Rodriguez12, J. Rose13, T. Schreiner14, M. Waltz15, T.C. Casper16, E. Waubant1

1Neurology, University of California, San Francisco, San Francisco, 2Neurology, University of California, San Diego, San Diego, CA, 3Neurology, Cleveland Clinic, Cleveland, OH, 4Neurology, State University of New York at Buffalo, Buffalo, NY, 5Pediatrics, Loma Linda University, Loma Linda, CA, 6Neurology, Boston Children's Hospital, 7Neurology, Massachusetts General Hospital, Boston, MA, 8Neurology, Washington University in Saint Louis, Saint Louis, MO, 9Nursing, University of Alabama at Birmingham, Birmingham, AL, 10Neurology, New York University Langone Medical Center, New York, NY, 11Neurology, Texas Children's Hospital, Houston, TX, 12Neurology, Mayo Clinic, Rochester, MN, 13Neurology, University of Utah, Salt Lake City, UT, 14Neurology, University of Colorado, Aurora, CO, 15Biostatistician II, 16Pediatrics, University of Utah, Salt Lake City, UT, United States

Introduction: Treatment of pediatric MS is challenging as most disease-modifying therapies (DMT) lack efficacy data in children, and there are no comparative effectiveness studies to guide initial DMT choice.
Objectives: We aim to assess the real-world effectiveness of initial treatment with newer compared to injectable DMTs on disease activity in MS and CIS treated before 18 years.
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) DMT. 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 was modeled with negative binomial regression for number of events on initial DMT, adjusted for PS quintile. Time to new/enlarging T2 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 initial therapy, 197 with a newer and 544 with an injectable DMT. Those started on newer DMT were older at onset (14.3 vs injectable 13.4 years), less likely to have a monofocal first event (37% vs injectable 55%), and more likely to have MS (87% vs injectable 79%). 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 DMT had significantly lower relapse rate than those started on injectable DMT (rate ratio 0.45, 95% CI 0.29-0.70, p< 0.001). Those started on newer DMT also had lower rate of new/enlarging T2 (HR 0.52, 95% CI 0.37-0.73) and gadolinium enhancing lesions (HR 0.38, 95% CI 0.23-0.62) than those on injectable DMT.
Conclusions: Initial treatment of children with MS/CIS with newer DMTs led to better disease activity control compared to initial therapy with injectables, supporting greater effectiveness of newer therapies. Data on long-term safety of newer DMTs is required.
Disclosure: Study funded by the National Multiple Sclerosis Society (HC-1509-06233 [Dr. Casper]). Dr. Krysko is funded by a Sylvia Lawry Physician Fellowship from the National Multiple Sclerosis Society (FP-1605-08753). The funders did not have a role in the design or analysis of this study.
Dr. Kristen M Krysko is supported by the Sylvia Lawry award from the National Multiple Sclerosis Society, and a Biogen MS fellowship grant.
Dr. Jennifer Graves has received recent grant and clinical trial support from the National MS Society, Race to Erase MS, UCSF CTSI RAP program, Biogen, and Genentech. She has received honoraria from Biogen and Genzyme for non-promotional trainee education events. She has received personal fees from Novartis and Celgene.
Dr. Mary Rensel has served as a consultant/speaker for Biogen, Teva, Genzyme, and Novartis; research support from Medimmune.
Dr. Bianca Weinstock-Guttman has served as a consultant/speaker for Biogen, Teva, Novartis, Genzyme, Genentech, and EMD Serono; research support from Biogen, Teva, Novartis, Genentech, and EMD Serono.
Dr. Alice Rutatangwa is supported by a Biogen MS fellowship grant.
Dr. Gregory Aaen has participated in clinical trials funded by Biogen.
Dr. Leslie Benson has received funding for research unrelated to this work for a Biogen sponsored clinical trial, and Boston Children´s Hospital office of faculty development grant. She has also acted as a paid consultant to the national Vaccine Injury Compensation Program.
Dr. Tanuja Chitnis is an advisory board member for Biogen, Novartis, and Sanofi-Genzyme; has received research support from Biogen, Novartis, Octave, Serono and Verily; has participated in clinical trials sponsored by Sanofi-Genzyme and Novartis.
Dr. Mark Gorman has participated in clinical trials funded by Novartis and Biogen, and received research funding from Pfizer.
Dr. Manu Goyal has received fees for providing consultations on medicolegal cases related to neuroradiology and has IBM Stock.
Dr. Yolanda Harris reports no disclosures relevant to the abstract.
Dr. Lauren Krupp received payments as a consultant for Biogen, Novartis, Everyday Health, Genentech, Gerson Lehman, Sanofi; served as an uncompensated consultant for Celgene, and received licensing payments from biotechnology and pharmaceutical companies for the fatigue severity scale.
Dr. Timothy Lotze has served as a consultant/speaker for Biogen.
Dr. Soe Mar reports no disclosures relevant to the abstract.
Dr. Manikum Moodley reports no disclosures relevant to the abstract.
Dr. Moses Rodriguez reports no disclosures relevant to the abstract.
Dr. John Rose has research support from NMSS, NIH, Guthy Jackson Foundation, PCORI, Teva Neuroscience, Biogen and VA.
Dr. Teri Schreiner has participated in trials funded by Biogen and MSDx.
Mr. Michael Waltz reports no disclosures relevant to the abstract.
Dr. T. Charles Casper reports no disclosures relevant to the abstract.
Dr. Emmanuelle Waubant has participated in multicenter clinical trials funded by Genentech and Biogen. She has current support from the NIH, NMSS, PCORI, and Race to Erase MS.

Abstract: 249

Type: Free Communications

Abstract Category: Clinical aspects of MS - Paediatric MS

K.M. Krysko1, J.S. Graves1,2, M. Rensel3, B. Weinstock-Guttman4, A. Rutatangwa1, G. Aaen5, L. Benson6, T. Chitnis7, M. Gorman6, M. Goyal8, Y. Harris9, L. Krupp10, T. Lotze11, S. Mar8, M. Moodley3, M. Rodriguez12, J. Rose13, T. Schreiner14, M. Waltz15, T.C. Casper16, E. Waubant1

1Neurology, University of California, San Francisco, San Francisco, 2Neurology, University of California, San Diego, San Diego, CA, 3Neurology, Cleveland Clinic, Cleveland, OH, 4Neurology, State University of New York at Buffalo, Buffalo, NY, 5Pediatrics, Loma Linda University, Loma Linda, CA, 6Neurology, Boston Children's Hospital, 7Neurology, Massachusetts General Hospital, Boston, MA, 8Neurology, Washington University in Saint Louis, Saint Louis, MO, 9Nursing, University of Alabama at Birmingham, Birmingham, AL, 10Neurology, New York University Langone Medical Center, New York, NY, 11Neurology, Texas Children's Hospital, Houston, TX, 12Neurology, Mayo Clinic, Rochester, MN, 13Neurology, University of Utah, Salt Lake City, UT, 14Neurology, University of Colorado, Aurora, CO, 15Biostatistician II, 16Pediatrics, University of Utah, Salt Lake City, UT, United States

Introduction: Treatment of pediatric MS is challenging as most disease-modifying therapies (DMT) lack efficacy data in children, and there are no comparative effectiveness studies to guide initial DMT choice.
Objectives: We aim to assess the real-world effectiveness of initial treatment with newer compared to injectable DMTs on disease activity in MS and CIS treated before 18 years.
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) DMT. 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 was modeled with negative binomial regression for number of events on initial DMT, adjusted for PS quintile. Time to new/enlarging T2 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 initial therapy, 197 with a newer and 544 with an injectable DMT. Those started on newer DMT were older at onset (14.3 vs injectable 13.4 years), less likely to have a monofocal first event (37% vs injectable 55%), and more likely to have MS (87% vs injectable 79%). 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 DMT had significantly lower relapse rate than those started on injectable DMT (rate ratio 0.45, 95% CI 0.29-0.70, p< 0.001). Those started on newer DMT also had lower rate of new/enlarging T2 (HR 0.52, 95% CI 0.37-0.73) and gadolinium enhancing lesions (HR 0.38, 95% CI 0.23-0.62) than those on injectable DMT.
Conclusions: Initial treatment of children with MS/CIS with newer DMTs led to better disease activity control compared to initial therapy with injectables, supporting greater effectiveness of newer therapies. Data on long-term safety of newer DMTs is required.
Disclosure: Study funded by the National Multiple Sclerosis Society (HC-1509-06233 [Dr. Casper]). Dr. Krysko is funded by a Sylvia Lawry Physician Fellowship from the National Multiple Sclerosis Society (FP-1605-08753). The funders did not have a role in the design or analysis of this study.
Dr. Kristen M Krysko is supported by the Sylvia Lawry award from the National Multiple Sclerosis Society, and a Biogen MS fellowship grant.
Dr. Jennifer Graves has received recent grant and clinical trial support from the National MS Society, Race to Erase MS, UCSF CTSI RAP program, Biogen, and Genentech. She has received honoraria from Biogen and Genzyme for non-promotional trainee education events. She has received personal fees from Novartis and Celgene.
Dr. Mary Rensel has served as a consultant/speaker for Biogen, Teva, Genzyme, and Novartis; research support from Medimmune.
Dr. Bianca Weinstock-Guttman has served as a consultant/speaker for Biogen, Teva, Novartis, Genzyme, Genentech, and EMD Serono; research support from Biogen, Teva, Novartis, Genentech, and EMD Serono.
Dr. Alice Rutatangwa is supported by a Biogen MS fellowship grant.
Dr. Gregory Aaen has participated in clinical trials funded by Biogen.
Dr. Leslie Benson has received funding for research unrelated to this work for a Biogen sponsored clinical trial, and Boston Children´s Hospital office of faculty development grant. She has also acted as a paid consultant to the national Vaccine Injury Compensation Program.
Dr. Tanuja Chitnis is an advisory board member for Biogen, Novartis, and Sanofi-Genzyme; has received research support from Biogen, Novartis, Octave, Serono and Verily; has participated in clinical trials sponsored by Sanofi-Genzyme and Novartis.
Dr. Mark Gorman has participated in clinical trials funded by Novartis and Biogen, and received research funding from Pfizer.
Dr. Manu Goyal has received fees for providing consultations on medicolegal cases related to neuroradiology and has IBM Stock.
Dr. Yolanda Harris reports no disclosures relevant to the abstract.
Dr. Lauren Krupp received payments as a consultant for Biogen, Novartis, Everyday Health, Genentech, Gerson Lehman, Sanofi; served as an uncompensated consultant for Celgene, and received licensing payments from biotechnology and pharmaceutical companies for the fatigue severity scale.
Dr. Timothy Lotze has served as a consultant/speaker for Biogen.
Dr. Soe Mar reports no disclosures relevant to the abstract.
Dr. Manikum Moodley reports no disclosures relevant to the abstract.
Dr. Moses Rodriguez reports no disclosures relevant to the abstract.
Dr. John Rose has research support from NMSS, NIH, Guthy Jackson Foundation, PCORI, Teva Neuroscience, Biogen and VA.
Dr. Teri Schreiner has participated in trials funded by Biogen and MSDx.
Mr. Michael Waltz reports no disclosures relevant to the abstract.
Dr. T. Charles Casper reports no disclosures relevant to the abstract.
Dr. Emmanuelle Waubant has participated in multicenter clinical trials funded by Genentech and Biogen. She has current support from the NIH, NMSS, PCORI, and Race to Erase MS.

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