Search

Introduction: Ocrelizumab (OCR) is a highly effective treatment of multiple sclerosis (MS), and B cell repopulation profiles suggest that it might be used as an immune reconstitution therapy. However, data on disease recurrence after stopping treatment with OCR are scarce. Our objective was to evaluate the recurrence of disease activity after OCR discontinuation., Methods: In this multicenter retrospective cohort study, we included MS patients who discontinued OCR, without switching to another treatment, for twelve months or more, after having received at least one full dosage of 600 mg. We defined focal inflammation as the occurrence of a clinical relapse or significant MRI activity (≥3 new T2 lesions or ≥2 contrast-enhancing lesions)., Results: We included 53 MS patients; 41 relapsing remitting (RRMS), 5 secondary progressive (SPMS) and 7 primary progressive (PPMS) patients. Median follow-up period after OCR discontinuation was 16 months. We only observed focal inflammation after discontinuation in RRMS patients; 2.4 % (1/41) patients presented with significant MRI activity and matching clinical symptoms, and 7.3 % (3/41) patients presented with a suspected clinical relapse without radiological activity: a total of 9.8 % (4/41) at a median time of 17 months after the last infusion., Discussion: We found focal inflammation after discontinuation of OCR in 4 (9.8 %) of the RRMS patients, of which 1 was radiologically confirmed. Our observations highlight that recurrence of focal inflammation seems low but discontinuation may not be appropriate for everyone. Further larger studies are important to determine the immune reconstitution therapy potential of OCR., Competing Interests: Declaration of competing interest E. Coerver reports no disclosures. L. Schoof reports no disclosures. L. Hogenboom reports no disclosures. M. Wessels reports no disclosures. P. v. Ruyven reports no disclosures. A. v. Samkar reports no disclosures. J. Mostert reports no disclosures. Z. v. Kempen reports no disclosures. B. v. Oosten reports no disclosures. B. Wokke reports no disclosures. E. Tallantyre has received honorarium for consulting work from Biogen, Janssen, Merck, Novartis, and Roche. She has received travel grants to attend or speak at educational meetings from Biogen, Merck, Roche, Takeda and Novartis. KM. Myrh has received speaker honoraria from Alexion, Biogen, Novartis, or Sanofi and has participated in clinical trials organized by Biogen, Merck, Novartis, Roche, and Sanofi. O. Torkildsen received speaker honoraria from Biogen, Merck, Sanofi, Teva, Gilead, Janssen and Novartis; and has participated in clinical trials organized by Biogen, Merck, Sanofi, Novartis, and Roche. J. Killestein received consulting fees for F. Hoffmann-La Roche, Biogen, Teva, Merck, Novartis and Sanofi/Genzyme (payments to institution); reports speaker relationships with F. Hoffmann-La Roche, Biogen, Teva, Merck, Novartis and Sanofi/Genzyme (payments to institution); adjudication committee of MS clinical trials of Immunic (payments to institution). I. Smets received honoraria from Merck, Biogen Idec and Sanofi. E. Strijbis has received speaker fees from Merck and Novartis., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

B-cell depleting therapies are frequently used as high efficacy treatments for multiple sclerosis (MS). We will elaborate on current data and future perspectives of one of the most studied anti-CD20 therapies concerning personalization. Currently, multiple randomized controlled trails are recruiting patients, with three different treatment strategies concerning the dose or the dosing interval of ocrelizumab. These strategies involve higher dosing, B-cell tailored dosing and discontinuation of ocrelizumab. We propose a roadmap (Figure 1), that will incorporate results of current trials to address the current knowledge gaps in pursuit of a more efficient use of anti-CD20 therapies in MS., Competing Interests: Declaration of competing interest Laura Hogenboom and Zoé L.E. van Kempen declare that there is no conflict of interest. Tomas Kalincik served on scientific advisory boards for MS International Federation and World Health Organisation, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. Amit Bar-Or: received personal fees for advisory board participation and/or consulting from Abata, Accure, Atara Biotherapeutics, Biogen, BMS/Celgene/Receptos, GlaxoSmithKline, Gossamer, Horizon Therapeutics, Immunic, Janssen/Actelion, Medimmune, Merck/EMD Serono, Novartis, Roche/Genentech, Sangamo, Sanofi-Genzyme, Viracta; and grant support to the University of Pennsylvania from Biogen Idec, Roche/Genentech, Merck/EMD Serono and Novartis. J. Killestein: received research grants for multicentre investigator initiated trials DOT-MS trial, ClinicalTrials.gov Identifier: NCT04260711 (ZonMW) and BLOOMS trial (ZonMW and Treatmeds), ClinicalTrials.gov Identifier: NCT05296161); received consulting fees for F. Hoffmann-La Roche Ltd, Biogen, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution); reports speaker relationships with F. Hoffmann-La Roche Ltd, Biogen, Immunic, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution); adjudication committee of MS clinical trials of Immunic (payments to institution only)., (Copyright © 2024 Elsevier B.V. All rights reserved.)