Impact of Siponimod on Clinical and Radiological Parameters of Secondary Progressive Multiple Sclerosis: A Real-World Prospective Study
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background and Purpose Secondary progressive multiple sclerosis (SPMS) presents with a challenging clinical phenotype, and siponimod has a potential to treat the active clinical phenotype of this disease. This single-center longitudinal study aimed to determine the therapeutic effects of siponimod in patients with active SPMS over 12 months. Methods The clinical and radiological parameters of 50 patients with active SPMS treated using siponimod were assessed at baseline and after a 1-year follow-up period using the annual relapse rate (ARR), the Expanded Disability Status Scale (EDSS), the occurrence of gadolinium-enhanced lesion (GdE+), the Modified Fatigue Impact Scale (MFIS), and the Symbol Digit Modalities Test. The urine bladder postvoid residual (PVR) volume was also measured in a subcohort of 39 participants. Participants with an EDSS score ≥5.0 at baseline were finally assessed separately in prespecified subgroup analyses. Results There were significant reductions in ARR (p<0.001), GdE+ (p<0.001), and MFIS score (p=0.001) during the follow-up period. The progression of physical and cognitive disabilities remained stable (p>0.05). The PVR-volume analysis revealed a significant decrease in urine bladder PVR volume (p<0.001). These observations were consistent for the subgroup with EDSS score ≥5.0. Conclusions Siponimod demonstrated efficacy in reducing ARR, GdE+, fatigue levels, and PVR volume, while maintaining stability in the cognitive and physical disability statuses of patients with SPMS. Similar findings were documented in the subgroup with EDSS score ≥5.0.
Abstract
Background and Purpose Secondary progressive multiple sclerosis (SPMS) presents with a challenging clinical phenotype, and siponimod has a potential to treat the active clinical phenotype of this disease. This single-center longitudinal study aimed to determine the therapeutic effects of siponimod in patients with active SPMS over 12 months. Methods The clinical and radiological parameters of 50 patients with active SPMS treated using siponimod were assessed at baseline and after a 1-year follow-up period using the annual relapse rate (ARR), the Expanded Disability Status Scale (EDSS), the occurrence of gadolinium-enhanced lesion (GdE+), the Modified Fatigue Impact Scale (MFIS), and the Symbol Digit Modalities Test. The urine bladder postvoid residual (PVR) volume was also measured in a subcohort of 39 participants. Participants with an EDSS score ≥5.0 at baseline were finally assessed separately in prespecified subgroup analyses. Results There were significant reductions in ARR (p<0.001), GdE+ (p<0.001), and MFIS score (p=0.001) during the follow-up period. The progression of physical and cognitive disabilities remained stable (p>0.05). The PVR-volume analysis revealed a significant decrease in urine bladder PVR volume (p<0.001). These observations were consistent for the subgroup with EDSS score ≥5.0. Conclusions Siponimod demonstrated efficacy in reducing ARR, GdE+, fatigue levels, and PVR volume, while maintaining stability in the cognitive and physical disability statuses of patients with SPMS. Similar findings were documented in the subgroup with EDSS score ≥5.0.
참고문헌 (34)
- Reich DS, "Multiple sclerosis", N Engl J Med, 378, pp.169~180 (2018)
- Kappos L, "Siponimod versus placebo in secondary progressive multiple sclerosis(EXPAND) : a double-blind, randomised, phase 3 study", Lancet, 391, pp.1263~1273 (2018)
- Klineova S, "Clinical course of multiple sclerosis", Cold Spring Harb Perspect Med, 8, pp.a028928~ (2018)
- Lassmann H, "Pathogenic mechanisms associated with different clinical courses of multiple sclerosis", Front Immunol, 9, pp.3116~ (2019)
- Caseby SCL, "Transition to secondary progressive multiple sclerosis : the consequences for patients and healthcare systems, a healthcare professional survey", Health Sci Rep, 5, pp.e474~ (2022)
- Confavreux C, "McAlpine’s Multiple Sclerosis", pp.183~272 (2006), Churchill Livingstone
- Oh J, "Diagnosis and management of secondary-progressive multiple sclerosis : time for change", Neurodegener Dis Manag, 9, pp.301~317 (2019)
- Hollen CW, "The future of progressive multiple sclerosis therapies", Fed Pract, 37, pp.S43~S49 (2020)
- Inojosa H, "A focus on secondary progressive multiple sclerosis(SPMS) : challenges in diagnosis and definition", J Neurol, 268, pp.1210~1221 (2021)
- Behrangi N, "Mechanism of siponimod : anti-inflammatory and neuroprotective mode of action", Cells, 8, pp.24~ (2019)
- O’Sullivan C, "The dual S1PR1", S1PR5drug BAF312(Siponimod)attenuates demyelination in organotypic slice cultures, 2016, pp.13, 31~
- Vališ M, "The benefits and risks of switching from fingolimod to siponimod for the treatment of relapsing-remitting and secondary progressive multiple sclerosis", Drugs R D, 23, pp.331~338 (2023)
- Regner-Nelke L, "Real-world evidence on siponimod treatment in patients with secondary progressive multiple sclerosis", Neurol Res Pract, 4, pp.55~ (2022)
- Faul F, "G*Power 3 : a flexible statistical power analysis program for the social, behavioral, and biomedical sciences", Behav Res Methods, 39, pp.175~191 (2007)
- Bayas A, "Disease-modifying therapies for relapsing", active secondary progressive multiple sclerosis-a review of population-specific evidence from randomized clinical trials, 2023, pp.16, 17562864221146836~
- "MAYZENT- siponimod tablet, film coated"[URL]
- World Medical Association, "World Medical Association Declaration of Helsinki : ethical principles for medical research involving human subjects", JAMA, 310, pp.2191~2194 (2013)
- Kurtzke JF, "Rating neurologic impairment in multiple sclerosis : an expanded disability status scale(EDSS)", Neurology, 33, pp.1444~1452 (1983)
- Messinis L, "Symbol digit modalities test : Greek normative data for the oral and written version and discriminative validity in patients with multiple sclerosis", Arch Clin Neuropsychol, 36, pp.117~125 (2021)
- Bakalidou D, "Validity and reliability of the Greek version of the Modified Fatigue Impact Scale in multiple sclerosis patients", Int J Rehabil Res, 37, pp.271~276 (2014)
- Monti Bragadin M, "Lower urinary tract dysfunction in patients with multiple sclerosis : a post-void residual analysis of 501 cases", Mult Scler Relat Disord, 45, pp.102378~ (2020)
- Çinar BP, "What we learned from the history of multiple sclerosis measurement : Expanded Disability Status Scale", Noro Psikiyatr Ars, 55(Suppl 1), pp.S69~S75 (2018)
- IBM Corporation, "IBM SPSS Statistics for Windows, Version 28.0", IBM Corporation, ~ (2021)
- D’Amico E, "Injectable versus oral first-line multiple sclerosis therapies : knows and unknowns from observational studies", Neural Regen Res, 17, pp.567~568 (2022)
- Selmaj K, "Siponimod for patients with relapsing-remitting multiple sclerosis(BOLD) : an adaptive, dose-ranging, randomised, phase 2 study", Lancet Neurol, 12, pp.756~767 (2013)
- Gasperini C, "Unraveling treatment response in multiple sclerosis : a clinical and MRI challenge", Neurology, 92, pp.180~192 (2019)
- Wattjes MP, "Evidence-based guidelines : MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis--establishing disease prognosis and monitoring patients", Nat Rev Neurol, 11, pp.597~606 (2015)
- Rovira A, "Magnetic resonance monitoring of lesion evolution in multiple sclerosis", Ther Adv Neurol Disord, 6, pp.298~310 (2013)
- Kleiter I, "The transitional phase of multiple sclerosis : characterization and conceptual framework", Mult Scler Relat Disord, 44, pp.102242~ (2020)
- Scott LJ, "Siponimod : a review in secondary progressive multiple sclerosis", CNS Drugs, 34, pp.1191~1200 (2020)
- Basavarajappa D, "Anti-inflammatory effects of siponimod in a mouse model of excitotoxicity-induced retinal injury", Mol Neurobiol, 60, pp.7222~7237 (2023)
- Cohan SL, "The two sides of siponimod : evidence for brain and immune mechanisms in multiple sclerosis", CNS Drugs, 36, pp.703~719 (2022)
- Benedict RHB, "Siponimod and cognition in secondary progressive multiple sclerosis : EXPAND secondary analyses", Neurology, 96, pp.e376~e386 (2021)
- Domurath B, "Neurourological assessment in people with multiple sclerosis(MS) : a new evaluated algorithm", Mult Scler Relat Disord, 44, pp.102248~ (2020)