Long-Term Treatment With Ocrelizumab in Patients With Early-Stage Relapsing MS Nine-Year Data From the OPERA Studies Open-Label Extension

被引:1
|
作者
Cerqueira, Joao J. [1 ]
Berthele, Achim [2 ]
Cree, Bruce A. C. [3 ]
Filippi, Massimo [4 ,5 ]
Pardo, Gabriel [6 ]
Pearson, Owen R. [7 ]
Traboulsee, Anthony [8 ]
Ziemssen, Tjalf [9 ]
Vollmer, Timothy [10 ]
Bernasconi, Corrado [11 ]
Mandel, Corey R. [12 ]
Kulyk, Inessa [11 ]
Chognot, Cathy [11 ]
Raposo, Catarina [11 ]
Schneble, Hans-Martin [11 ]
Thanei, Gian-Andrea [11 ]
Incera, Elodie [13 ]
Havrdova, Eva K. [14 ,15 ,16 ]
机构
[1] Univ Minho, Life & Hlth Sci Res Inst, Sch Med, Braga, Portugal
[2] Tech Univ Munich, Sch Med, Dept Neurol, Munich, Germany
[3] Univ Calif San Francisco, UCSF Weill Inst Neurosci, Dept Neurol, San Francisco, CA USA
[4] IRCCS San Raffaele Sci Inst, Div Neurosci, Neurorehabil Unit, Neuroimaging Res Unit,Neurophysiol Serv,Neurol Uni, Milan, Italy
[5] Univ Vita Salute San Raffaele, Milan, Italy
[6] Oklahoma Med Res Fdn Multiple Sclerosis, Ctr Excellence, Oklahoma City, OK USA
[7] Morriston Hosp, Dept Neurol, Swansea, Wales
[8] Univ British Columbia, Div Neurol, Vancouver, BC, Canada
[9] Tech Univ Dresden, Univ Clin Carl Gustav Carus, Dept Neurol, Carl Gustav Carus Univ Hosp, Dresden, Germany
[10] Univ Colorado, Dept Neurol, Rocky Mt Multiple Sclerosis Ctr, Anschutz Med Campus, Denver, CO USA
[11] F Hoffmann La Roche Ltd, Basel, Switzerland
[12] Genentech Inc, San Francisco, CA USA
[13] IQVIA Inc, Paris, France
[14] Gen Univ Hosp, Med Fac 1, Dept Neurol, Prague, Czech Republic
[15] Gen Univ Hosp, Med Fac 1, Ctr Clin Neurosci, Prague, Czech Republic
[16] Charles Univ Prague, Prague, Czech Republic
关键词
MULTIPLE-SCLEROSIS; POPULATION; THERAPY; ATROPHY; SAFETY;
D O I
10.1212/WNL.0000000000210142
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Objectives Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS). Methods Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received >= 1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies. Patients were randomized to OCR or interferon beta-1a for 96 weeks (double-blind controlled treatment period [DBP]), before switching to OCR in the open-label extension (OLE). Efficacy assessments included no evidence of disease activity (NEDA-3), 24-week confirmed disability progression (CDP), MRI lesion activity, change in whole-brain volume; with safety outcomes assessed over a 9-year treatment period. Results Overall, 757 patients were included (interferon-treated n = 382, mean age 36.3 years, 65.7% female; OCR-treated n = 375, mean age 35.5 years, 64.0% female); 505 of 757 (66.7%) completed 9 years of follow-up. The difference in NEDA status between OCR-treated and interferon-treated patients achieved during the DBP (72.5% and 43.8%, respectively, odds ratio 3.48, 95% CI 2.52-4.81) was maintained throughout the 7-year OLE (48.2% vs 25.7%; odds ratio 2.72, 95% CI 1.94-3.82). No 24-week CDP was observed in 78.7% of OCR-treated patients over 9 years. Brain volume loss over the entire study period remained numerically higher among patients starting OCR later (p = 0.09 at OLE at week 336). During the DBP, safety profiles in both groups were similar; no new safety signals were observed during the OLE. Over >9 years of continuous OCR treatment, the rate of infections remained low and stable over time. Discussion A higher proportion of OCR-treated patients achieved NEDA status compared with interferon-treated patients during the DBP, which was maintained throughout the OLE. After switching to OCR, disability accrual and brain volume loss among interferon-treated patients became similar to the OCR-OCR group, but disability and brain volume loss accrued during interferon treatment were not recovered. Possible study limitations include assessment bias due to unmaintained blinding during the OLE. These data support OCR as first-line therapy for these patients. Classification of Evidence This study provides Class II evidence that OCR delays disease progression in treatment-naive patients with early-stage RMS.
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页数:11
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