Soe Mar, Massimiliano Valeriani, Barbara Steinborn, Teri Schreiner, Emmanuelle Waubant, Massimo Filippi, Katarzyna Kotulska, Maria Mazurkiewicz-Beldzinska, Bouchra El Azzouzi, Chien-Ju Lin, Yun-An Shen, Heidemarie Kletzl, Joanna Evershed, Alexandra Hogea, Corinne Manlius, Ulrike Bonati, Brenda Banwell
{"title":"Ocrelizumab治疗小儿复发-缓解型多发性硬化的剂量选择：OPERETTA I研究的结果","authors":"Soe Mar, Massimiliano Valeriani, Barbara Steinborn, Teri Schreiner, Emmanuelle Waubant, Massimo Filippi, Katarzyna Kotulska, Maria Mazurkiewicz-Beldzinska, Bouchra El Azzouzi, Chien-Ju Lin, Yun-An Shen, Heidemarie Kletzl, Joanna Evershed, Alexandra Hogea, Corinne Manlius, Ulrike Bonati, Brenda Banwell","doi":"10.1007/s00415-024-12879-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).</p><p><strong>Methods: </strong>Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.</p><p><strong>Primary endpoints: </strong>pharmacokinetics, pharmacodynamics (CD19<sup>+</sup> B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.</p><p><strong>Results: </strong>A total of 23 patients (cohort 1: n = 6, age 10-12 years, BW 27.0-39.0 kg; cohort 2: n = 17, age 11-17 years, BW 42.1-108.4 kg) were enrolled. Median treatment duration was 120 (range, 24-193) weeks at the primary analysis cutoff (October 5, 2023). Overall, the pharmacokinetic data were within the range observed at 600 mg in adult patients with MS; however, the exposure at 300 mg in patients < 40 kg was lower than with 600 mg in patients ≥ 40 kg. Shifting the cutoff to 35 kg would provide better exposure to patients with 35-40 kg body weight. Sustained, near-complete B-cell depletion was observed. The safety profile was consistent with that in adults. EDSS scores remained stable; no clinical relapses were observed.</p><p><strong>Conclusion: </strong>A dosing regimen of 300 mg ocrelizumab for patients < 35 kg, and 600 mg for patients ≥ 35 kg (every 24 weeks), was selected for the phase 3 OPERETTA II trial (NCT05123703).</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT04075266.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 2","pages":"137"},"PeriodicalIF":4.8000,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735518/pdf/","citationCount":"0","resultStr":"{\"title\":\"Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study.\",\"authors\":\"Soe Mar, Massimiliano Valeriani, Barbara Steinborn, Teri Schreiner, Emmanuelle Waubant, Massimo Filippi, Katarzyna Kotulska, Maria Mazurkiewicz-Beldzinska, Bouchra El Azzouzi, Chien-Ju Lin, Yun-An Shen, Heidemarie Kletzl, Joanna Evershed, Alexandra Hogea, Corinne Manlius, Ulrike Bonati, Brenda Banwell\",\"doi\":\"10.1007/s00415-024-12879-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).</p><p><strong>Methods: </strong>Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.</p><p><strong>Primary endpoints: </strong>pharmacokinetics, pharmacodynamics (CD19<sup>+</sup> B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.</p><p><strong>Results: </strong>A total of 23 patients (cohort 1: n = 6, age 10-12 years, BW 27.0-39.0 kg; cohort 2: n = 17, age 11-17 years, BW 42.1-108.4 kg) were enrolled. Median treatment duration was 120 (range, 24-193) weeks at the primary analysis cutoff (October 5, 2023). Overall, the pharmacokinetic data were within the range observed at 600 mg in adult patients with MS; however, the exposure at 300 mg in patients < 40 kg was lower than with 600 mg in patients ≥ 40 kg. Shifting the cutoff to 35 kg would provide better exposure to patients with 35-40 kg body weight. Sustained, near-complete B-cell depletion was observed. The safety profile was consistent with that in adults. EDSS scores remained stable; no clinical relapses were observed.</p><p><strong>Conclusion: </strong>A dosing regimen of 300 mg ocrelizumab for patients < 35 kg, and 600 mg for patients ≥ 35 kg (every 24 weeks), was selected for the phase 3 OPERETTA II trial (NCT05123703).</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT04075266.</p>\",\"PeriodicalId\":16558,\"journal\":{\"name\":\"Journal of Neurology\",\"volume\":\"272 2\",\"pages\":\"137\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-01-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735518/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00415-024-12879-z\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00415-024-12879-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study.
Background: The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).
Methods: Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.
Results: A total of 23 patients (cohort 1: n = 6, age 10-12 years, BW 27.0-39.0 kg; cohort 2: n = 17, age 11-17 years, BW 42.1-108.4 kg) were enrolled. Median treatment duration was 120 (range, 24-193) weeks at the primary analysis cutoff (October 5, 2023). Overall, the pharmacokinetic data were within the range observed at 600 mg in adult patients with MS; however, the exposure at 300 mg in patients < 40 kg was lower than with 600 mg in patients ≥ 40 kg. Shifting the cutoff to 35 kg would provide better exposure to patients with 35-40 kg body weight. Sustained, near-complete B-cell depletion was observed. The safety profile was consistent with that in adults. EDSS scores remained stable; no clinical relapses were observed.
Conclusion: A dosing regimen of 300 mg ocrelizumab for patients < 35 kg, and 600 mg for patients ≥ 35 kg (every 24 weeks), was selected for the phase 3 OPERETTA II trial (NCT05123703).
期刊介绍：
The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field.
In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials.
Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.
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