Abstract
Background Fingolimod is a daily oral medication used to treat relapsing multiple sclerosis (MS). Clinicians often adopt less frequent dosing for patients with profound drug-induced lymphopenia or other adverse events. Data on the effectiveness of alternate dose fingolimod are limited. Methods We conducted a multicenter, retrospective, observational study at 14 sites and identified 170 patients with MS taking alternate doses of fingolimod for ≥1 month. Clinical and radiologic outcomes were collected and compared during daily and alternate fingolimod dosing. Results Profound lymphopenia (77%), liver function abnormalities (9%), and infections (7%) were the most common reasons for patients to switch to alternate fingolimod dosing. The median followup was 12 months on daily dose and 14 months on alternate dose. Most patients (64%) took fingolimod every other day during alternate dosing. Disease activity was similar on alternate dose compared to daily dose: annualized relapse rate was 0.1 on daily dose vs 0.2 on alternate dose (p = 0.25); proportion of patients with contrast-enhancing MRI lesions was 7.6% on daily vs 9.4% on alternate (p = 0.55); proportion of patients with cumulative MS activity (clinical and radiologic disease) was 13.5% on daily vs 18.2% on alternate (p = 0.337). Patients who developed contrast-enhancing lesions while on daily dose were at higher risk for breakthrough disease while on alternate dose fingolimod (odds ratio 11.4, p < 0.001). Conclusions These data support the clinical strategy of alternate dosing of fingolimod in patients with good disease control but profound lymphopenia or other adverse events while on daily dose. Classification of Evidence This study provides Class IV evidence that for patients with MS on daily dose fingolimod with adverse events, alternate dose fingolimod is associated with disease activity similar to daily dose fingolimod.
| Original language | English |
|---|---|
| Pages (from-to) | 102-107 |
| Number of pages | 6 |
| Journal | Neurology: Clinical Practice |
| Volume | 8 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2018 |
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In: Neurology: Clinical Practice, Vol. 8, No. 2, 2018, p. 102-107.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Effectiveness of alternative dose fingolimod for multiple sclerosis
AU - Longbrake, Erin E.
AU - Kantor, Daniel
AU - Pawate, Siddharama
AU - Bradshaw, Michael J.
AU - Von Geldern, Gloria
AU - Chahin, Salim
AU - Cross, Anne H.
AU - Parks, Becky J.
AU - Rice, Marc
AU - Khoury, Samia J.
AU - Yamout, Bassem
AU - Zeineddine, Maya
AU - Russell-Giller, Shira
AU - Caminero-Rodriguez, Ana
AU - Edwards, Keith
AU - Lathi, Ellen
AU - VanderKodde, Danita
AU - Meador, William
AU - Berkovich, Regina
AU - Ge, Lily
AU - Bacon, Tamar E.
AU - Kister, Ilya
N1 - Funding Information: E.E. Longbrake serves on scientific advisory boards and/or as a consultant for Sanofi, Genzyme, Teva, Genentech, EMD Serono, and Biogen; has received speaker honoraria from Genzyme and Biogen; and receives support from NIH and National MS Society. D. Kantor serves on a scientific advisory board for Corrona MS; has served as a consultant for, on the speakers' bureaus for, and/or received speaker honoraria from Avanir, Bayer, Biogen, Mylan, Novartis, EMD Serono, AbbVie, and Sanofi Genzyme; and receives research support from Genzyme. S. Pawate serves on a scientific advisory board for and receives research support from Biogen. M. J. Bradshaw serves on the editorial board of Continuum: Lifelong Learning in Neurology. G. von Geldern has received research support from Novartis. S. Chahin serves on the speakers' bureau for Teva and receives research support from PhRMA Foundation. A.H. Cross serves on scientific advisory boards for Roche/ Genentech; has received speaker honoraria from EMD Serono and AbbVie; has served as an Associate Editor for Annals Clinical Translational Neurology and serves on the editorial boards of Brain Pathology and Journal of Neuroimmunology; is an author on US patent 15060-630 “Methods for simultaneous multi-angular relaxometry of tissue using magnetic resonance imaging”; has served as a consultant for Biogen, Sanofi Aventis/Genzyme, Novartis, Teva, Bayer, Gerson Lehrman Group, Guidepoint Global, LLC, EMD Serono, AbbVie, Genentech, and At Point of Care; has received honoraria for other activities from Projects in Knowledge, Prime Education, Inc., Race To ERASE MS, the Conrad N. Hilton Foundation, and WebMD; serves on the Board of Governors for Consortium of MS Centers; and receives research support from Roche, Teva Neuroscience, Biogen, NIH/NINDS, Barnes-Jewish Hospital Foundation, and Conrad N Hilton Foundation. B.J. Parks was employed by Washington University in St. Louis at the time of this research and is currently employed by Biogen as Associate Medical Director, Drug Safety; has served as a consultant for Optum Rx; has served on scientific advisory boards for Genentech, Novartis, and EMD Serono; and holds stock/stock options in Biogen, Illumina, Bioverativ (spun off from BGN), BMS, Express Scripts, Regeneron, Ionis, Vertex, and Rexahn. Her spouse receives research funding from NIH, the Edward P. Evans Foundation, the Taub Foundation, and the V. Foundation. M. Rice receives/has received research support from Biogen Idec and Sanofi-Genzyme. S.J. Khoury serves as a Section Editor for Clinical Immunology and for Current Treatment Options in Neurology, Associate Editor for Annals of Neurology, and on the editorial board of MS Journal; and receives research support from Novartis and CNRS-Lebanon. B. Yamout has received honoraria for speaking and consulting for Biogen, Novartis, Sanofi Genzyme, Roche, Merck, and Bayer; and receives research support from Novartis, Merck, Sanofi Genzyme, Bayer, Biogen, and Roche. M. Zeineddine has received speaker honoraria from Novartis, Biologix, and Merck. S. Russell-Giller and A. Caminero report no disclosures. K. Edwards has received funding for travel from Biogen and Genzyme; is employed as Director, MS Center of Northeastern NY; has served as a consultant for Biogen, Genzyme, and EMD Serono; has served on speakers' bureaus for Biogen and Genzyme; and receives research support from Biogen, Genentech/Roche, Genzyme, Novartis, and Eli Lilly. E. Lathi serves on speakers' bureaus for Genentech, Biogen, Teva, Sanofi Genzyme, and Novartis. D. Vanderkodde has received funding for travel and speaker honoraria from Biogen-Idec; served as a consultant for Sanofi Genzyme; and serves on the speakers' bureau for Biogen-Idec. W. Meador receives research support from Genzyme and MedImmune. R. Berkovich serves on scientific advisory boards for MSAA, NMSS, Biogen, Genentech, Novartis, Sanofi Genzyme, Bayer, Mallinckrodt, and Teva; has received funding for travel and speaker honoraria from Acorda, Avanir, Bayer, Biogen, Sanofi, Genentech, Mallinckrodt, Novartis, and Teva; serves as an Associate Editor for Journal of Medical Case Reports; and serves on speakers' bureaus for Acorda, Biogen, Sanofi, Novartis, and Teva. L. Ge reports no disclosures. T.E. Bacon served on a scientific advisory board for Genentech; is author on a patent re: Harnessing altered intestinal microbial compositions for diagnosis, prevention, and treatment of multiple sclerosis; and receives research support from Actelion, Alexion, Biogen, EMD Serono, Genzyme, Novartis, Teva Pharmaceuticals, Patient-Centered Outcomes Research Institute, NIH, and Guthy-Jackson Charitable Foundation. I. Kister serves on scientific advisory boards for Biogen Idec and Genentech; has served as a consultant for Biogen Idec; and has received research support from Biogen-Idec, Serono, Novartis, Genzyme, Guthy-Jackson Charitable Foundation, and National Multiple Sclerosis Society. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp. Funding Information: E.E. Longbrake serves on scientific advisory boards and/or as a consultant for Sanofi, Genzyme, Teva, Genentech, EMD Serono, and Biogen; has received speaker honoraria from Genzyme and Biogen; and receives support from NIH and National MS Society. D. Kantor serves on a scientific advisory board for Corrona MS; has served as a consultant for, on the speakers’ bureaus for, and/or received speaker honoraria from Avanir, Bayer, Biogen, Mylan, Novartis, EMD Serono, Abb-Vie, and Sanofi Genzyme; and receives research support from Genzyme. S. Pawate serves on a scientific advisory board for and receives research support from Biogen. M. J. Bradshaw serves on the editorial board of Continuum: Lifelong Learning in Neurology. G. von Geldern has received research support from Novartis. S. Chahin serves on the speakers’ bureau for Teva and receives research support from PhRMA Foundation. A.H. Cross serves on scientific advisory boards for Roche/ Genentech; has received speaker honoraria from EMD Serono and AbbVie; has served as an Associate Editor for Annals Clinical Translational Neurology and serves on the editorial boards of Brain Pathology and Journal of Neuroimmunology; is an author on US patent 15060-630 “Methods for simultaneous multi-angular relaxometry of tissue using magnetic resonance imaging”; has served as a consultant for Biogen, Sanofi Aventis/Genzyme, Novartis, Teva, Bayer, Gerson Lehrman Group, Guidepoint Global, LLC, EMD Serono, AbbVie, Genentech, and At Point of Care; has received honoraria for other activities from Projects in Knowledge, Prime Education, Inc., Race To ERASE MS, the Conrad N. Hilton Foundation, and WebMD; serves on the Board of Governors for Consortium of MS Centers; and receives research support from Roche, Teva Neuroscience, Biogen, NIH/NINDS, Barnes-Jewish Hospital Foundation, and Conrad N Hilton Foundation. B.J. Parks was employed by Washington University in St. Louis at the time of this research and is currently employed by Biogen as Associate Medical Director, Drug Safety; has served as a consultant for Optum Rx; has served on scientific advisory boards for Genentech, Novartis, and EMD Serono; and holds stock/stock options in Biogen, Illumina, Bioverativ (spun off from BGN), BMS, Express Scripts, Regeneron, Ionis, Vertex, and Rexahn. Her spouse receives research funding from NIH, the Edward P. Evans Foundation, the Taub Foundation, and the V. Foundation. M. Rice receives/has received research support from Biogen Idec and Sanofi-Genzyme. S.J. Khoury serves as a Section Editor for Clinical Immunology and for Current Treatment Options in Neurology, Associate Editor for Annals of Neurology, and on the editorial board of MS Journal; and receives research support from Novartis and CNRS-Lebanon. B. Yamout has received honoraria for speaking and consulting for Biogen, Novartis, Sanofi Genzyme, Roche, Merck, and Bayer; and receives research support from Novartis, Merck, Sanofi Genzyme, Bayer, Biogen, and Roche. M. Zeineddine has received speaker honoraria from Novartis, Biologix, and Merck. S. Russell-Giller and A. Caminero report no disclosures. K. Edwards has received funding for travel from Biogen and Genzyme; is employed as Director, MS Center of Northeastern NY; has served as a consultant for Biogen, Genzyme, and EMD Serono; has served on speakers’ bureaus for Biogen and Genzyme; and receives research support from Biogen, Genentech/Roche, Genzyme, Novartis, and Eli Lilly. E. Lathi serves on speakers’ bureaus for Genentech, Biogen, Teva, Sanofi Genzyme, and Novartis. D. Vanderkodde has received funding for travel and speaker honoraria from Biogen-Idec; served as a consultant for Sanofi Genzyme; and serves on the speakers’ bureau for Biogen-Idec. W. Meador receives research support from Genzyme and MedImmune. R. Berkovich serves on scientific advisory boards for MSAA, NMSS, Biogen, Genentech, Novartis, Sanofi Genzyme, Bayer, Mallinckrodt, and Teva; has received funding for travel and speaker honoraria from Acorda, Avanir, Bayer, Biogen, Sanofi, Genentech, Mallinckrodt, Novartis, and Teva; serves as an Associate Editor for Journal of Medical Case Reports; and serves on speakers’ bureaus for Acorda, Biogen, Sanofi, Novartis, and Teva. L. Ge reports no disclosures. T.E. Bacon served on a scientific advisory board for Genentech; is author on a patent re: Harnessing altered intestinal microbial compositions for diagnosis, prevention, and treatment of multiple sclerosis; and receives research support from Actelion, Alexion, Biogen, EMD Serono, Genzyme, Novartis, Teva Pharmaceuticals, Patient-Centered Outcomes Research Institute, NIH, and Guthy-Jackson Charitable Foundation. I. Kister serves on scientific advisory boards for Biogen Idec and Genentech; has served as a consultant for Biogen Idec; and has received research support from Biogen-Idec, Serono, Novartis, Genzyme, Guthy-Jackson Charitable Foundation, and National Multiple Sclerosis Society. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp. Publisher Copyright: 102 Copyright © 2018 American Academy of Neurology
PY - 2018
Y1 - 2018
N2 - Background Fingolimod is a daily oral medication used to treat relapsing multiple sclerosis (MS). Clinicians often adopt less frequent dosing for patients with profound drug-induced lymphopenia or other adverse events. Data on the effectiveness of alternate dose fingolimod are limited. Methods We conducted a multicenter, retrospective, observational study at 14 sites and identified 170 patients with MS taking alternate doses of fingolimod for ≥1 month. Clinical and radiologic outcomes were collected and compared during daily and alternate fingolimod dosing. Results Profound lymphopenia (77%), liver function abnormalities (9%), and infections (7%) were the most common reasons for patients to switch to alternate fingolimod dosing. The median followup was 12 months on daily dose and 14 months on alternate dose. Most patients (64%) took fingolimod every other day during alternate dosing. Disease activity was similar on alternate dose compared to daily dose: annualized relapse rate was 0.1 on daily dose vs 0.2 on alternate dose (p = 0.25); proportion of patients with contrast-enhancing MRI lesions was 7.6% on daily vs 9.4% on alternate (p = 0.55); proportion of patients with cumulative MS activity (clinical and radiologic disease) was 13.5% on daily vs 18.2% on alternate (p = 0.337). Patients who developed contrast-enhancing lesions while on daily dose were at higher risk for breakthrough disease while on alternate dose fingolimod (odds ratio 11.4, p < 0.001). Conclusions These data support the clinical strategy of alternate dosing of fingolimod in patients with good disease control but profound lymphopenia or other adverse events while on daily dose. Classification of Evidence This study provides Class IV evidence that for patients with MS on daily dose fingolimod with adverse events, alternate dose fingolimod is associated with disease activity similar to daily dose fingolimod.
AB - Background Fingolimod is a daily oral medication used to treat relapsing multiple sclerosis (MS). Clinicians often adopt less frequent dosing for patients with profound drug-induced lymphopenia or other adverse events. Data on the effectiveness of alternate dose fingolimod are limited. Methods We conducted a multicenter, retrospective, observational study at 14 sites and identified 170 patients with MS taking alternate doses of fingolimod for ≥1 month. Clinical and radiologic outcomes were collected and compared during daily and alternate fingolimod dosing. Results Profound lymphopenia (77%), liver function abnormalities (9%), and infections (7%) were the most common reasons for patients to switch to alternate fingolimod dosing. The median followup was 12 months on daily dose and 14 months on alternate dose. Most patients (64%) took fingolimod every other day during alternate dosing. Disease activity was similar on alternate dose compared to daily dose: annualized relapse rate was 0.1 on daily dose vs 0.2 on alternate dose (p = 0.25); proportion of patients with contrast-enhancing MRI lesions was 7.6% on daily vs 9.4% on alternate (p = 0.55); proportion of patients with cumulative MS activity (clinical and radiologic disease) was 13.5% on daily vs 18.2% on alternate (p = 0.337). Patients who developed contrast-enhancing lesions while on daily dose were at higher risk for breakthrough disease while on alternate dose fingolimod (odds ratio 11.4, p < 0.001). Conclusions These data support the clinical strategy of alternate dosing of fingolimod in patients with good disease control but profound lymphopenia or other adverse events while on daily dose. Classification of Evidence This study provides Class IV evidence that for patients with MS on daily dose fingolimod with adverse events, alternate dose fingolimod is associated with disease activity similar to daily dose fingolimod.
UR - http://www.scopus.com/inward/record.url?scp=85064184258&partnerID=8YFLogxK
U2 - 10.1212/CPJ.0000000000000434
DO - 10.1212/CPJ.0000000000000434
M3 - Article
C2 - 29708225
AN - SCOPUS:85064184258
SN - 2163-0402
VL - 8
SP - 102
EP - 107
JO - Neurology: Clinical Practice
JF - Neurology: Clinical Practice
IS - 2
ER -