PMID- 34553320 OWN - NLM STAT- MEDLINE DCOM- 20220330 LR - 20240405 IS - 1878-7479 (Electronic) IS - 1933-7213 (Print) IS - 1878-7479 (Linking) VI - 18 IP - 4 DP - 2021 Oct TI - Predictors of Ocrelizumab Effectiveness in Patients with Multiple Sclerosis. PG - 2579-2588 LID - 10.1007/s13311-021-01104-8 [doi] AB - Data regarding effectiveness and safety of ocrelizumab in the post-marking setting are lacking. The aim of our study was to provide effectiveness and safety data of ocrelizumab treatment in patients with relapsing-remitting (RR-) and progressive multiple sclerosis (PMS) and to evaluate clinical and immunological predictors of early treatment response. In this single-center prospective observational study, we investigated effectiveness outcomes (time-to-confirmed disability worsening, time-to-first relapse, time-to-first evidence of MRI activity and time-to-first evidence of disease activity), clinical and immunological predictors of early treatment response, and incidence of adverse events (AEs). One hundred and fifty-three subjects were included (93 RRMS; 84 females). Median follow-up was 1.9 (1.3-2.7). At 2-year follow-up (FU), disability worsening-free survival were 90.5%, 64.7%, and 68.8% for RRMS, primary-progressive MS (PPMS), and secondary-progressive MS (SPMS) patients, respectively. At 2-year FU, 67.1%, 72.7%, and 81.3% of patients with RRMS, PPMS, and SPMS were free of MRI activity, with NEDA-3 percentages of 62.1%, 54.6%, and 55.1%, respectively. Lower baseline EDSS was independently associated with a reduced risk of disability worsening (HR(95%CI) = 1.45(1.05-2.00), p = 0.024) and previous treatment exposure was independently associated with increased probability of radiological activity (HR = 2.53(1.05-6.10), p = 0.039). At 6-month FU, CD8 + cell decrease was less pronounced in patients with inflammatory activity (p = 0.022). Six patients (3.9%) discontinued ocrelizumab due to severe AEs. Our findings suggest that ocrelizumab is an effective treatment in real-world patients with RRMS and PMS, with a manageable safety profile. Better outcomes were observed in treatment-naive patients and in patients with a low baseline disability level. Depletion of CD8 + cells could underlie early therapeutic effects of ocrelizumab. CI - (c) 2021. The Author(s). FAU - Cellerino, Maria AU - Cellerino M AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. FAU - Boffa, Giacomo AU - Boffa G AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. FAU - Lapucci, Caterina AU - Lapucci C AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. AD - Laboratory of Experimental Neurosciences, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. FAU - Tazza, Francesco AU - Tazza F AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. FAU - Sbragia, Elvira AU - Sbragia E AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. FAU - Mancuso, Elisabetta AU - Mancuso E AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. FAU - Bruschi, Nicolo AU - Bruschi N AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. FAU - Minguzzi, Simona AU - Minguzzi S AD - Ospedale Policlinico San Martino-IRCCS, Genoa, Italy. FAU - Ivaldi, Federico AU - Ivaldi F AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. FAU - Poire, Ilaria AU - Poire I AD - Ospedale Policlinico San Martino-IRCCS, Genoa, Italy. FAU - Laroni, Alice AU - Laroni A AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. AD - Ospedale Policlinico San Martino-IRCCS, Genoa, Italy. FAU - Mancardi, Gianluigi AU - Mancardi G AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. AD - Scientific Clinical Institutes Maugeri IRCCS, Pavia, Italy. FAU - Capello, Elisabetta AU - Capello E AD - Ospedale Policlinico San Martino-IRCCS, Genoa, Italy. FAU - Uccelli, Antonio AU - Uccelli A AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. AD - Ospedale Policlinico San Martino-IRCCS, Genoa, Italy. FAU - Novi, Giovanni AU - Novi G AD - Ospedale Policlinico San Martino-IRCCS, Genoa, Italy. FAU - Inglese, Matilde AU - Inglese M AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo Paolo Daneo 3, 16100, Genoa, Italy. m.inglese@unige.it. AD - Departments of Neurology, Radiology and Neuroscience, Icahn School of Medicine at Mount Sinai, NY, New York, USA. m.inglese@unige.it. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20210922 PL - United States TA - Neurotherapeutics JT - Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics JID - 101290381 RN - 0 (Antibodies, Monoclonal, Humanized) RN - A10SJL62JY (ocrelizumab) SB - IM MH - Antibodies, Monoclonal, Humanized/adverse effects MH - Female MH - Humans MH - *Multiple Sclerosis/drug therapy MH - *Multiple Sclerosis, Chronic Progressive/drug therapy MH - *Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging/drug therapy PMC - PMC8457546 OTO - NOTNLM OT - Advanced multiple sclerosis OT - CD8 OT - Highly active multiple sclerosis OT - Multiple sclerosis OT - Ocrelizumab EDAT- 2021/09/24 06:00 MHDA- 2022/03/31 06:00 PMCR- 2021/09/22 CRDT- 2021/09/23 07:04 PHST- 2021/08/05 00:00 [accepted] PHST- 2021/09/24 06:00 [pubmed] PHST- 2022/03/31 06:00 [medline] PHST- 2021/09/23 07:04 [entrez] PHST- 2021/09/22 00:00 [pmc-release] AID - S1878-7479(23)00724-9 [pii] AID - 1104 [pii] AID - 10.1007/s13311-021-01104-8 [doi] PST - ppublish SO - Neurotherapeutics. 2021 Oct;18(4):2579-2588. doi: 10.1007/s13311-021-01104-8. Epub 2021 Sep 22.