Abstract
Background and purpose: In the REFLEX trial (ClinicalTrials.gov identifier: NCT00404352), patients with a first clinical demyelinating event (FCDE) displayed significantly delayed onset of multiple sclerosis (MS; McDonald criteria) when treated with subcutaneous interferon beta-1a (sc IFN β-1a) versus placebo. This post hoc analysis evaluated the effect of sc IFN β-1a on spatio-temporal evolution of disease activity, assessed by changes in T2 lesion distribution, in specific brain regions of such patients and its relationship with conversion to MS. Methods: Post hoc analysis of baseline and 24-month magnetic resonance imaging data from FCDE patients who received sc IFN β-1a 44 μg once or three times weekly, or placebo in the REFLEX trial. Patients were grouped according to McDonald MS status (converter/non-converter) or treatment (sc IFN β-1a/placebo). For each patient group, a baseline lesion probability map (LPM) and longitudinal new/enlarging and shrinking/disappearing LPMs were created. Lesion location/frequency of lesion occurrence were assessed in the white matter. Results: At Month 24, lesion frequency was significantly higher in the anterior thalamic radiation (ATR) and corticospinal tract (CST) of converters versus non-converters (p < 0.05). Additionally, the overall distribution of new/enlarging lesions across the brain at Month 24 was similar in placebo- and sc IFN β-1a-treated patients (ratio: 0.95). Patients treated with sc IFN β-1a versus placebo showed significantly lower new lesion frequency in specific brain regions (cluster corrected): ATR (p = 0.025), superior longitudinal fasciculus (p = 0.042), CST (p = 0.048), and inferior longitudinal fasciculus (p = 0.048). Conclusions: T2 lesion distribution in specific brain locations predict conversion to McDonald MS and show significantly reduced new lesion occurrence after treatment with sc IFN β-1a in an FCDE population.
| Original language | English |
|---|---|
| Pages (from-to) | 2024-2035 |
| Number of pages | 12 |
| Journal | European Journal of Neurology |
| Volume | 29 |
| Issue number | 7 |
| Early online date | 11 Mar 2022 |
| DOIs | |
| Publication status | Published - Jul 2022 |
Bibliographical note
Funding Information:HV has received research support from Merck, Novartis, Pfizer, and Teva, consulting fees from Merck, and speaker honoraria from Novartis; all funds were paid to his institution. AV has received research support from Merck. MSF has received honoraria or consultation fees from Alexion, Atara Biotherapeutics, Bayer, BeiGene, BMS (Celgene), EMD Inc., Canada (an affiliate of Merck KGaA), Hoffmann La‐Roche, Janssen (J&J), Merck, Novartis, Pendopharm, and Sanofi‐Genzyme; has been a member of a company advisory board, board of directors, or other similar group for Alexion, Atara Biotherapeutics, Bayer, BeiGene, BMS (Celgene), Clene Nanomedicine, Hoffmann La‐Roche, Janssen (J&J), McKesson, Merck, Novartis, and Sanofi‐Genzyme; and has participated in a company sponsored speaker's bureau for EMD Serono Inc., USA (an affiliate of Merck KGaA) and Sanofi‐Genzyme. BMJU has received consultation fees from Biogen, Genzyme, Merck, Novartis, Roche, and Teva. LK’s institution (University Hospital, University of Basel) has received the following exclusively for research support: steering committee, advisory board, and consultancy fees (Actelion [Janssen/J&J], Bayer, Biogen, BMS, Genzyme, Janssen, Merck, Novartis, Roche, Sanofi, Santhera, and TG Therapeutics); speaker fees (Bayer, Biogen, Merck, Novartis, Roche, and Sanofi); support of educational activities (Allergan, Bayer, Biogen, CSL Behring, Desitin, Genzyme, Merck, Novartis, Roche, Pfizer, Sanofi, Shire, and Teva); license fees for Neurostatus products; and grants (Bayer, Biogen, European Union, InnoSwiss, Merck, Novartis, Roche, Swiss MS Society, and Swiss National Research Foundation). GC has received consulting fees from Bayer, Biogen, Merck, Novartis, Receptos, Roche/Genentech, Sanofi‐Aventis, and Teva Pharmaceutical Industries Ltd; lecture fees from Bayer, Biogen, Merck, Novartis, Sanofi‐Aventis, Serono Symposia International Foundation, and Teva Pharmaceutical Industries Ltd; and trial grant support from Bayer, Biogen, Merck, Novartis, Receptos, Roche/Genentech, Sanofi‐Aventis, and Teva Pharmaceutical Industries Ltd. AS is an employee of Merck Healthcare KGaA, Darmstadt, Germany. DJ is an employee of Merck Serono Ltd, Feltham, UK (an affiliate of Merck KGaA). MPS has received consulting fees from Biogen, GeNeuro, Genzyme, MedDay, Merck, Novartis, Roche, and Teva. FB is supported by the NIHR Biomedical Research Centre at UCLH and is a consultant to Biogen, Combinostics, IXICO, Merck, and Roche. NDeS is a consultant for Biogen, Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva; has grants or grants pending from FISM and Novartis, is on the speakers' bureaus of Biogen, Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva; and has received travel funds from Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva. MB, RTB, GG, and LL report no disclosures.
Funding Information:
This study was supported by Merck (CrossRef Funder ID: 10.13039/100009945 ) with a joint grant to the University of Siena, Siena, Italy and the Amsterdam UMC (Location VUmc), Amsterdam, The Netherlands. Medical writing support was provided by Sarah Wetherill, Caroline Spencer, and Steve Winter of inScience Communications, Springer Healthcare Ltd, UK, and funded by Merck Healthcare KGaA, Darmstadt, Germany. Frederik Barkhof acknowledges support from the NIHR Biomedical Research Centre at UCLH. Open Access Funding provided by Universita degli Studi di Siena within the CRUI‐CARE Agreement.
Publisher Copyright:
© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.