9575eff73d7f9824deeb0141e0abd2e7 pmc_10607533.pdf 86c374c2c92dbabd988e20bdf9f784621ab15265 pmc_10607533.pdf 01caa7f9220da83902006f7001263dd729d2456b270e39636cf9d2eb0d390f72 pmc_10607533.pdf Title: The Need for the Closer Monitoring of Novel Drugs in MS: A Siponimod Retrospective Cohort Study (Realhes Study) Subject: Background: Severe cases of lymphopenia have been reported during siponimod clinical trials, which may negatively impact its benefit/risk profile. Objective: We aimed to evaluate the incidence of lymphopenia following the initiation of siponimod treatment in clinical practice. The secondary objectives included the analysis of factors predisposing to and the clinical relevance of lymphopenia events. Methods: In this multicenter retrospective cohort study, information collected from the medical records of 129 patients with MS from 15 tertiary hospitals in Spain who initiated treatment with Siponimod were followed-up for at least 3 months, including at least one lymphocyte count evaluation per patient. Results: Of the 129 patients, 121 (93.6%) reported lymphopenia events, including 110 (85.3%) with grade 3 and 11 (8.5%) with grade 4 lymphopenia, higher than those reported in the pivotal clinical trial (73.3% and 3.3% for grade 3 and grade 4 lymphopenia, respectively). The study included an unexpectedly high proportion of male subjects (72.9%), which might have led to an underestimation of the actual magnitude of the risk. Conclusions: In this study, the incidence and severity of lymphopenia after starting siponimod treatment were higher than those reported in previous clinical trials. Therefore, our results reinforce the need for the closer monitoring of novel MS drugs in clinical practice, as well as larger and longer follow-up studies to properly characterize this risk. Keywords: multiple sclerosis; siponimod; pharmacovigilance; lymphopenia; real-world evidence Author: Arantxa Sancho-López, Belén Ruiz-Antorán, Teresa Iglesias Hernangómez, Almudena Ramírez-García, Irene Gómez Estevez, Judith Sanabria-Cabrera, Roser Llop Rius, Consuelo Pedrós, Diana Campodonico, Silvia Jiménez-Jorge, Amelia García Luque, Lucienne Costa Frossad França, Eva Montané, Ana Aldea-Perona, Nieves Téllez Lara, Montserrat Bosch Ferrer, Consuelo Rodriguez Jiménez, Elvira Bonilla-Toyos, Julia Sabín Muñoz, Cristina Avendaño-Solá, María Rosario Blasco Quilez and on behalf of the REALHES-Study Group Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Oct 21 12:13:57 2023 CEST ModDate: Mon Oct 23 03:43:39 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1351384 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID 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edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Appendix A Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Info: Title: The Need for the Closer Monitoring of Novel Drugs in MS: A Siponimod Retrospective Cohort Study (Realhes Study) Author: Arantxa Sancho-López, Belén Ruiz-Antorán, Teresa Iglesias Hernangómez, Almudena Ramírez-García, Irene Gómez Estevez, Judith Sanabria-Cabrera, Roser Llop Rius, Consuelo Pedrós, Diana Campodonico, Silvia Jiménez-Jorge, Amelia García Luque, Lucienne Costa Frossad França, Eva Montané, Ana Aldea-Perona, Nieves Téllez Lara, Montserrat Bosch Ferrer, Consuelo Rodriguez Jiménez, Elvira Bonilla-Toyos, Julia Sabín Muñoz, Cristina Avendaño-Solá, María Rosario Blasco Quilez and on behalf of the REALHES-Study Group Subject: Background: Severe cases of lymphopenia have been reported during siponimod clinical trials, which may negatively impact its benefit/risk profile. Objective: We aimed to evaluate the incidence of lymphopenia following the initiation of siponimod treatment in clinical practice. The secondary objectives included the analysis of factors predisposing to and the clinical relevance of lymphopenia events. Methods: In this multicenter retrospective cohort study, information collected from the medical records of 129 patients with MS from 15 tertiary hospitals in Spain who initiated treatment with Siponimod were followed-up for at least 3 months, including at least one lymphocyte count evaluation per patient. Results: Of the 129 patients, 121 (93.6%) reported lymphopenia events, including 110 (85.3%) with grade 3 and 11 (8.5%) with grade 4 lymphopenia, higher than those reported in the pivotal clinical trial (73.3% and 3.3% for grade 3 and grade 4 lymphopenia, respectively). The study included an unexpectedly high proportion of male subjects (72.9%), which might have led to an underestimation of the actual magnitude of the risk. Conclusions: In this study, the incidence and severity of lymphopenia after starting siponimod treatment were higher than those reported in previous clinical trials. Therefore, our results reinforce the need for the closer monitoring of novel MS drugs in clinical practice, as well as larger and longer follow-up studies to properly characterize this risk. 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