@article{824ad23cfb954e7a978e301f36a9d795,
title = "Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy in paediatric patients with multiple sclerosis: Results from the PARADIGMS study",
abstract = "Background: Reduction in absolute lymphocyte count (ALC) is expected with fingolimod treatment. Objective: To evaluate the effect of fingolimod 0.5 mg versus intramuscular interferon β-1a (30 μg) on ALC and its relationship with infections in paediatric-onset multiple sclerosis (POMS) up to 4 years. Methods: We assessed ALC at baseline, monthly till 3 months, and every 3 months (core phase) and with variable periodicity (extension phase) of Phase 3 PARADIGMS study (N = 215). Incidence rates (IRs) of infection-related adverse events (infAEs)/100 patient-years were analysed by on-study nadir ALC. Results: With fingolimod, ALC rapidly reduced to 29.9%–34.4% of baseline values within 2 weeks and remained stable thereafter; no relevant changes observed with interferon. IRs of infAEs were 67.6 with fingolimod and 61.8 with interferon; IR ratios with respect to interferon, overall: 1.09, by nadir ALC 0.2–0.4 × 109/L: 1.13 and >0.4 × 109/L: 0.91. Three patients had a single episode of ALC <0.2 × 109/L (core phase). No opportunistic infections were observed and infection risk did not increase during the extension phase. Conclusion: In paediatric patients, the overall incidence of infections was comparable between fingolimod and interferon. No association was observed between nadir ALC and infections in POMS, although sample size may have been too small to rule an association.",
keywords = "Fingolimod, clinical trial, infections, lymphocyte count, paediatric-onset multiple sclerosis, relapsing–remitting",
author = "Tanuja Chitnis and Brenda Banwell and Lauren Krupp and Arnold, {Douglas L.} and Amit Bar-Or and Wolfgang Br{\"u}ck and Gavin Giovannoni and Benjamin Greenberg and Angelo Ghezzi and Emmanuelle Waubant and Kevin Rostasy and Kumaran Deiva and Peter Huppke and Wolinsky, {Jerry S.} and Ying Zhang and Amin Azmon and Annik K-Laflamme and Rajesh Karan and Jutta G{\"a}rtner",
note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This study was funded by Novartis Pharma AG, Basel, Switzerland. Funding Information: The authors thank the patients and investigators who participated in the study. The authors take full responsibility for the content of the paper. The authors also thank Saimithra Thammera and Uma Kundu (both of Medical Communications, Novartis Healthcare Pvt. Ltd., Hyderabad, India) for writing assistance, editorial review assistance and in coordinating author review. All authors edited the manuscript for intellectual content, provided guidance during manuscript development and approved the final version submitted for publication. The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This study was funded by Novartis Pharma AG, Basel, Switzerland. Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: T.C. received personal compensation for advisory boards/consulting for F. Hoffman-La Roche, Biogen and Novartis, and financial support for research activities from Biogen, Merck Serono, Verily and Novartis. B.B. served as an unpaid consultant for Biogen Idec, Novartis, Teva Neuroscience, Merck Serono, Canadian MS Society Scientific Research Foundation, Canadian Multiple Sclerosis Society, National Multiple Sclerosis Society and Canadian Institutes of Health Research. She served as a remunerated central MRI reviewer for the present trial. L.K. received personal compensation for activities as a speaker, consultant and/or participant on an advisory board from Biogen Idec, Novartis, Teva Neuroscience and Multicell; royalty or licence fees from ER Squibb & Sons, Avenir, Johnson & Johnson and Osmotica; grant support from the National Multiple Sclerosis Society, National Institutes of Health and the Department of Defence; and research support from Novartis, Biogen Idec, Celgene Corporation and Genentech. She has also received support from the Lourie Foundation, Slomo and Cindy Silvian Foundation and the Multiple Sclerosis Foundation. D.L.A. received consultant fees from Acorda Therapeutics, Biogen, Celgene, GeNeuro, Genentech, F. Hoffmann-La Roche, Merck, Novartis, Roche, Sanofi, Teva and Wave Life Sciences; personal compensation from NeuroRx Research; and research support from Biogen, Immunotec and Novartis. A.B.-O. participated as a speaker at meetings sponsored by, received consulting fees and/or received grant support from Biogen Idec, F. Hoffmann-La Roche/Genentech, GlaxoSmithKline, Merck/EMD Serono, MedImmune, Novartis, Celgene/Receptos and Sanofi-Genzyme. W.B. received honoraria for lectures from Bayer Vital, Biogen, Merck Serono, Teva Pharma, Genzyme, Sanofi-Aventis and Novartis. He received funding for research projects by Teva Pharma, Biogen, Novartis and Genzyme. He serves on the editorial boards of Neuropathology and Applied Neurobiology, Multiple Sclerosis International and Therapeutic Advances in Neurological Disorders. G.G. is a steering committee member on the daclizumab trials for AbbVie, the BG12 and daclizumab trials for Biogen, the fingolimod and siponimod trials for Novartis, the laquinimod trials for Teva and the ocrelizumab trials for Roche. He has also received consultancy fees for advisory board meetings for oral cladribine trials for Merck KGaA, Genzyme-Sanofi, and in relation to DSMB activities for Synthon BV, as well as honoraria for speaking at the Physicians{\textquoteright} Summit and several medical education meetings. He is also the Co-Chief Editor of Multiple Sclerosis and Related Disorders (Elsevier). B.G. received compensation for consulting services from EMD Serono, Alexion, Celgene and Novartis; and grant support from Chugai, Biogen, Acorda, MedImmune, PCORI, NIH, Genentech, the Transverse Myelitis Association and Guthy Jackson Charitable Foundation. He serves as an unpaid member of the Transverse Myelitis Association board. A.G. received honoraria for speaking from Almirall, Biogen Idec, Merck Serono, Novartis, Genzyme and Sanofi-Aventis; and for consultancy from Merck Serono, Biogen Idec, Teva, F. Hoffmann-La Roche and Novartis. E.W. is funded by the NIH, NMSS, PCORI and Race to Erase MS. She volunteers on an advisory board for a Novartis trial. She is a site PI for clinical trials with Roche and Novartis. K.R. served as a consultant for the PARADIGMS study. K.D. received personal compensation for speaker activities from Novartis, Servier and Sanofi. P.H. received honoraria for lectures and consultancy fees from Bayer, Merck, Biogen and Novartis. J.S.W. served on advisory boards and data monitoring or steering committees, has held consulting agreements or has received speaker honoraria from Alkermes, Brainstorm Cell Therapeutics, EMD Serono, GeNeuro, GW Pharma Ltd, MedDay Pharmaceuticals, Novartis, Roche, Genentech and Sanofi Genzyme, and receives royalties for monoclonal antibodies out-licenced to Chemicon International through UTHealth. J.G., in the last 3 years, received honoraria for lectures and consultancy fees from Bayer, Biogen, Novartis, Sanofi and Teva as well as funding for a research project from Novartis. A.K.-L. was an employee of Novartis during the conduct of the study and development of the manuscript. Y.Z., A.A. and R.K. are employees of Novartis. Publisher Copyright: {\textcopyright} The Author(s), 2020.",
year = "2021",
month = may,
doi = "10.1177/1352458520936934",
language = "English (US)",
volume = "27",
pages = "922--932",
journal = "Multiple Sclerosis Journal",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "6",
}