Comparative Effectiveness of Natalizumab, Fingolimod, and Injectable Therapies in Pediatric-Onset Multiple Sclerosis: A Registry-Based Study
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
38447093
PubMed Central
PMC11033984
DOI
10.1212/wnl.0000000000208114
Knihovny.cz E-zdroje
- MeSH
- dítě MeSH
- dospělí MeSH
- fingolimod hydrochlorid * terapeutické užití MeSH
- lidé MeSH
- natalizumab terapeutické užití MeSH
- recidiva MeSH
- registrace MeSH
- retrospektivní studie MeSH
- roztroušená skleróza * farmakoterapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fingolimod hydrochlorid * MeSH
- natalizumab MeSH
BACKGROUND AND OBJECTIVES: Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses, and though patients with POMS usually recover from relapses better than adults, patients with POMS reach irreversible disability at a younger age than adult-onset patients. There have been few randomized, placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry. METHODS: This retrospective study included patients with POMS who initiated treatment with an injectable DMT, natalizumab, or fingolimod between January 1, 2006, and May 3, 2021. Patients were matched using inverse probability treatment weighting. The primary outcome was time to first relapse from index therapy initiation. Secondary study outcomes included annualized relapse rate; proportions of relapse-free patients at 1, 2, and 5 years; time to treatment discontinuation; and times to 24-week confirmed disability worsening and confirmed disability improvement. RESULTS: A total of 1,218 patients with POMS were included in this analysis. Patients treated with fingolimod had a significantly lower risk of relapse than patients treated with injectable DMTs (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29-0.83; p = 0.008). After adjustment for prior DMT experience in the unmatched sample, patients treated with natalizumab had a significantly lower risk of relapse than patients treated either with injectable DMTs (HR, 0.15; 95% CI 0.07-0.31; p < 0.001) or fingolimod (HR, 0.37; 95% CI 0.14-1.00; p = 0.049). The adjusted secondary study outcomes were generally consistent with the primary outcome or with previous observations. The findings in the inverse probability treatment weighting-adjusted patient populations were confirmed in multiple sensitivity analyses. DISCUSSION: Our analyses of relapse risk suggest that natalizumab is more effective than fingolimod in the control of relapses in this population with high rates of new inflammatory activity, consistent with previous studies of natalizumab and fingolimod in adult-onset patients and POMS. In addition, both fingolimod and natalizumab were more effective than first-line injectable therapies. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patients with POMS treated with natalizumab had a lower risk of relapse than those with fingolimod.
Zobrazit více v PubMed
Multiple Sclerosis International Federation. Atlas of MS 3rd edition. Part 2: clinical management of multiple sclerosis around the world; 2021. Accessed October 31, 2022. msif.org/wp-content/uploads/2021/05/Atlas-3rd-Edition-clinical-management-report-EN-5-5-21.pdf.
McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. J Am Med Assoc. 2021;325(8):765-779. doi:10.1001/jama.2020.26858 PubMed DOI
Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D, University of British Columbia MS Clinic Neurologists. Early onset multiple sclerosis: a longitudinal study. Neurology. 2002;59(7):1006-1010. doi:10.1212/wnl.59.7.1006 PubMed DOI
Chitnis T, Glanz B, Jaffin S, Healy B. Demographics of pediatric-onset multiple sclerosis in an MS center population from the Northeastern United States. Mult Scler. 2009;15(5):627-631. doi:10.1177/1352458508101933 PubMed DOI
Harding KE, Liang K, Cossburn MD, et al. . Long-term outcome of paediatric-onset multiple sclerosis: a population-based study. J Neurol Neurosurg Psychiatry. 2013;84(2):141-147. doi:10.1136/jnnp-2012-303996 PubMed DOI
Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol. 2009;66(1):54-59. doi:10.1001/archneurol.2008.505 PubMed DOI
Alroughani R, Boyko A. Pediatric multiple sclerosis: a review. BMC Neurol. 2018;18(1):27. doi:10.1186/s12883-018-1026-3 PubMed DOI PMC
Benson LA, Healy BC, Gorman MP, et al. . Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years. Mult Scler Relat Disord. 2014;3(2):186-193. doi:10.1016/j.msard.2013.06.004 PubMed DOI
Renoux C, Vukusic S, Mikaeloff Y, et al. . Natural history of multiple sclerosis with childhood onset. N Engl J Med. 2007;356(25):2603-2613. doi:10.1056/NEJMoa067597 PubMed DOI
Wallach AI, Waltz M, Casper TC, et al. . Cognitive processing speed in pediatric-onset multiple sclerosis: baseline characteristics of impairment and prediction of decline. Mult Scler. 2020;26(14):1938-1947. doi:10.1177/1352458519891984 PubMed DOI
McKay KA, Friberg E, Razaz N, Alexanderson K, Hillert J. Long-term socioeconomic outcomes associated with pediatric-onset multiple sclerosis. JAMA Neurol. 2021;78(4):478-482. doi:10.1001/jamaneurol.2020.5520 PubMed DOI PMC
Baroncini D, Simone M, Iaffaldano P, et al. . Risk of persistent disability in patients with pediatric-onset multiple sclerosis. JAMA Neurol. 2021;78(6):726-735. doi:10.1001/jamaneurol.2021.1008 PubMed DOI PMC
Jakimovski D, Awan S, Eckert SP, Farooq O, Weinstock-Guttman B. Multiple sclerosis in children: differential diagnosis, prognosis, and disease-modifying treatment. CNS Drugs. 2022;36(1):45-59. doi:10.1007/s40263-021-00887-w PubMed DOI PMC
Bar-Or A, Hintzen RQ, Dale RC, Rostasy K, Bruck W, Chitnis T. Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases. Neurology. 2016;87(9 suppl 2):S12-S19. doi:10.1212/WNL.0000000000002821 PubMed DOI
Waubant E, Ponsonby AL, Pugliatti M, Hanwell H, Mowry EM, Hintzen RQ. Environmental and genetic factors in pediatric inflammatory demyelinating diseases. Neurology. 2016;87(9 suppl 2):S20-S27. doi:10.1212/WNL.0000000000003029 PubMed DOI
Margoni M, Rinaldi F, Perini P, Gallo P. Therapy of pediatric-onset multiple sclerosis: state of the art, challenges, and opportunities. Front Neurol. 2021;12:676095. doi:10.3389/fneur.2021.676095 PubMed DOI PMC
Baroncini D, Zaffaroni M, Moiola L, et al. . Long-term follow-up of pediatric MS patients starting treatment with injectable first-line agents: a multicentre, Italian, retrospective, observational study. Mult Scler. 2019;25(3):399-407. doi:10.1177/1352458518754364 PubMed DOI
Krysko KM, Graves J, Rensel M, et al. . Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US. Neurology. 2018;91(19):e1778-e1787. doi:10.1212/WNL.0000000000006471 PubMed DOI PMC
Gilenya® (Fingolimod) [prescribing Information]. Novartis Pharmaceuticals Corp; 2019.
Gilenya® (Fingolimod) [summary of Product Characteristics]. Novartis Pharma GmbH; 2018.
Chitnis T, Arnold DL, Banwell B, et al. . Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis. N Engl J Med. 2018;379(11):1017-1027. doi:10.1056/NEJMoa1800149 PubMed DOI
Banwell B, Reder AT, Krupp L, et al. . Safety and tolerability of interferon beta-1b in pediatric multiple sclerosis. Neurology. 2006;66(4):472-476. doi:10.1212/01.wnl.0000198257.52512.1a PubMed DOI
Ghezzi A, Amato MP, Capobianco M, et al. . Treatment of early-onset multiple sclerosis with intramuscular interferon beta-1a: long-term results. Neurol Sci. 2007;28(3):127-132. doi:10.1007/s10072-007-0804-2 PubMed DOI
Kornek B, Aboul-Enein F, Rostasy K, et al. . Natalizumab therapy for highly active pediatric multiple sclerosis. JAMA Neurol. 2013;70(4):469-475. doi:10.1001/jamaneurol.2013.923 PubMed DOI
Tenembaum SN, Banwell B, Pohl D, et al. . Subcutaneous interferon beta-1a in pediatric multiple sclerosis: a retrospective study. J Child Neurol. 2013;28(7):849-856. doi:10.1177/0883073813488828 PubMed DOI
Krysko KM, Graves JS, Rensel M, et al. . Real-world effectiveness of initial disease-modifying therapies in pediatric multiple sclerosis. Ann Neurol. 2020;88(1):42-55. doi:10.1002/ana.25737 PubMed DOI
Palavra F, Figueiroa S, Correia AS, et al. . TyPed study: natalizumab for the treatment of pediatric-onset multiple sclerosis in Portugal. Mult Scler Relat Disord. 2021;51:102865. doi:10.1016/j.msard.2021.102865 PubMed DOI
Simpson A, Mowry EM, Newsome SD. Early aggressive treatment approaches for multiple sclerosis. Curr Treat Options Neurol. 2021;23(7):19. doi:10.1007/s11940-021-00677-1 PubMed DOI PMC
Kalincik T, Butzkueven H. The MSBase registry: informing clinical practice. Mult Scler. 2019;25(14):1828-1834. doi:10.1177/1352458519848965 PubMed DOI
Butzkueven H, Chapman J, Cristiano E, et al. . MSBase: an international, online registry and platform for collaborative outcomes research in multiple sclerosis. Mult Scler. 2006;12(6):769-774. doi:10.1177/1352458506070775 PubMed DOI
Waubant E, Banwell B, Wassmer E, et al. . Clinical trials of disease-modifying agents in pediatric MS: opportunities, challenges, and recommendations from the IPMSSG. Neurology. 2019;92(22):e2538-e2549. doi:10.1212/WNL.0000000000007572 PubMed DOI PMC
Cohen JA, Trojano M, Mowry EM, Uitdehaag BM, Reingold SC, Marrie RA. Leveraging real-world data to investigate multiple sclerosis disease behavior, prognosis, and treatment. Mult Scler. 2020;26(1):23-37. doi:10.1177/1352458519892555 PubMed DOI PMC
Schwartz CE, Grover SA, Powell VE, et al. . Risk factors for non-adherence to disease-modifying therapy in pediatric multiple sclerosis. Mult Scler. 2018;24(2):175-185. doi:10.1177/1352458517695469 PubMed DOI PMC
Baroncini D, Ghezzi A, Guaschino C, et al. . Long-term follow-up (up to 11 years) of an Italian pediatric MS cohort treated with Natalizumab: a multicenter, observational study. Neurol Sci. 2022;43(11):6415-6423. doi:10.1007/s10072-022-06211-8 PubMed DOI
Butzkueven H, Kappos L, Wiendl H, et al. . Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). J Neurol Neurosurg Psychiatry. 2020;91(6):660-668. doi:10.1136/jnnp-2019-322326 PubMed DOI PMC
Kalincik T, Horakova D, Spelman T, et al. . Switch to natalizumab versus fingolimod in active relapsing-remitting multiple sclerosis. Ann Neurol. 2015;77(3):425-435. doi:10.1002/ana.24339 PubMed DOI
He A, Spelman T, Jokubaitis V, et al. . Comparison of switch to fingolimod or interferon beta/glatiramer acetate in active multiple sclerosis. JAMA Neurol. 2015;72(4):405-413. doi:10.1001/jamaneurol.2014.4147 PubMed DOI
Kister I, Spelman T, Alroughani R, et al. . Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study. J Neurol Neurosurg Psychiatry. 2016;87(10):1133-1137. doi:10.1136/jnnp-2016-313760 PubMed DOI
Spelman T, Kalincik T, Zhang A, et al. . Comparative efficacy of switching to natalizumab in active multiple sclerosis. Ann Clin Transl Neurol. 2015;2(4):373-387. doi:10.1002/acn3.180 PubMed DOI PMC
Allan V, Ramagopalan SV, Mardekian J, et al. . Propensity score matching and inverse probability of treatment weighting to address confounding by indication in comparative effectiveness research of oral anticoagulants. J Comp Eff Res. 2020;9(9):603-614. doi:10.2217/cer-2020-0013 PubMed DOI
Arnold DL, Banwell B, Bar-Or A, et al. . Effect of fingolimod on MRI outcomes in patients with paediatric-onset multiple sclerosis: results from the phase 3 PARADIGMS study. J Neurol Neurosurg Psychiatry. 2020;91(5):483-492. doi:10.1136/jnnp-2019-322138 PubMed DOI PMC
Deiva K, Huppke P, Banwell B, et al. . Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS. J Neurol Neurosurg Psychiatry. 2020;91(1):58-66. doi:10.1136/jnnp-2019-321124 PubMed DOI PMC
Feng J, Rensel M. Review of the safety, efficacy and tolerability of fingolimod in the treatment of pediatric patients with relapsing-remitting forms of multiple sclerosis (RRMS). Pediatr Health Med Ther. 2019;10:141-146. doi:10.2147/PHMT.S220817 PubMed DOI PMC
Zaffaroni M. Fingolimod in pediatric-onset multiple sclerosis. Neurol Sci. 2021;42(suppl 1):1-4. doi:10.1007/s10072-021-05294-z PubMed DOI
Ziemssen T, Albrecht H, Haas J, et al. . Descriptive analysis of real-world data on fingolimod long-term treatment of young adult RRMS patients. Front Neurol. 2021;12:637107. doi:10.3389/fneur.2021.637107 PubMed DOI PMC
Cohen M, Mondot L, Bucciarelli F, et al. . BEST-MS: a prospective head-to-head comparative study of natalizumab and fingolimod in active relapsing MS. Mult Scler. 2021;27(10):1556-1563. doi:10.1177/1352458520969145 PubMed DOI
Butzkueven H, Licata S, Jeffery D, et al. . Natalizumab versus fingolimod for patients with active relapsing-remitting multiple sclerosis: results from REVEAL, a prospective, randomised head-to-head study. BMJ Open. 2020;10(10):e038861. doi:10.1136/bmjopen-2020-038861 PubMed DOI PMC
Guerra T, Caputo F, Orlando B, Paolicelli D, Trojano M, Iaffaldano P. Long-term comparative analysis of no evidence of disease activity (NEDA-3) status between multiple sclerosis patients treated with natalizumab and fingolimod for up to 4 years. Neurol Sci. 2021;42(11):4647-4655. doi:10.1007/s10072-021-05127-z PubMed DOI PMC
He A, Merkel B, Brown JWL, et al. . Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol. 2020;19(4):307-316. doi:10.1016/S1474-4422(20)30067-3 PubMed DOI
Brown JWL, Coles A, Horakova D, et al. . Association of initial disease-modifying therapy with later conversion to secondary progressive multiple sclerosis. JAMA. 2019;321(2):175-187. doi:10.1001/jama.2018.20588 PubMed DOI PMC