PMID- 34475123
OWN - NLM
STAT- MEDLINE
DCOM- 20211029
LR  - 20211217
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 97
IP  - 16
DP  - 2021 Oct 19
TI  - Safety of Ocrelizumab in Patients With Relapsing and Primary Progressive Multiple 
      Sclerosis.
PG  - e1546-e1559
LID - 10.1212/WNL.0000000000012700 [doi]
AB  - BACKGROUND AND OBJECTIVES: To report safety of ocrelizumab (OCR) up to 7 years in 
      patients with relapsing multiple sclerosis (RMS) and primary progressive multiple 
      sclerosis (PPMS) enrolled in clinical trials or treated in real-world 
      postmarketing settings. METHODS: Safety analyses are based on integrated clinical 
      and laboratory data for all patients who received OCR in 11 clinical trials, 
      including the controlled treatment and open-label extension (OLE) periods of the 
      phase 2 and 3 trials, plus the phase 3b trials VELOCE, CHORDS, CASTING, OBOE, 
      ENSEMBLE, CONSONANCE, and LIBERTO. For selected adverse events (AEs), additional 
      postmarketing data were used. Incidence rates of serious infections (SIs) and 
      malignancies were contextualized using multiple epidemiologic sources. RESULTS: 
      At data cutoff (January 2020), 5,680 patients with multiple sclerosis (MS) 
      received OCR (18,218 patient-years [PY] of exposure) in clinical trials. Rates 
      per 100 PY (95% confidence interval) of AEs (248; 246-251), serious AEs (7.3; 
      7.0-7.7), infusion-related reactions (25.9; 25.1-26.6), and infections (76.2; 
      74.9-77.4) were similar to those within the controlled treatment period of the 
      phase 3 trials. Rates of the most common serious AEs, including SIs (2.01; 
      1.81-2.23) and malignancies (0.46; 0.37-0.57), were consistent with the ranges 
      reported in epidemiologic data. DISCUSSION: Continuous administration of OCR for 
      up to 7 years in clinical trials, as well as its broader use for more than 3 
      years in the real-world setting, are associated with a favorable and manageable 
      safety profile, without emerging safety concerns, in a heterogeneous MS 
      population. CLASSIFICATION OF EVIDENCE: This analysis provides Class III evidence 
      that long-term, continuous treatment with OCR has a consistent and favorable 
      safety profile in patients with RMS and PPMS. This study is rated Class III 
      because of the use of OLE data and historical controls.
CI  - Copyright (c) 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Academy of Neurology.
FAU - Hauser, Stephen L
AU  - Hauser SL
AUID- ORCID: 0000-0002-4932-4001
AD  - From the Department of Neurology (S.L.H.), University of California, San 
      Francisco; Departments of Medicine, Clinical Research, Biomedicine and Biomedical 
      Engineering (L.K.), Research Center for Clinical Neuroimmunology and Neuroscience 
      Basel, University Hospital Basel, University of Basel, Switzerland; Department of 
      Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia 
      (CEMCAT), Vall d'Hebron University Hospital, Barcelona, Spain; F. Hoffmann-La 
      Roche Ltd. (L.C., C.C., R.H., H.K., N.P.), Basel, Switzerland; Genentech, Inc. 
      (A.P.), South San Francisco, CA; IQVIA Solutions Inc. (K.P.), Amsterdam, The 
      Netherlands; and Department of Neurology (J.S.W.), McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth). 
      stephen.hauser@ucsf.edu.
FAU - Kappos, Ludwig
AU  - Kappos L
AUID- ORCID: 0000-0003-4175-5509
AD  - From the Department of Neurology (S.L.H.), University of California, San 
      Francisco; Departments of Medicine, Clinical Research, Biomedicine and Biomedical 
      Engineering (L.K.), Research Center for Clinical Neuroimmunology and Neuroscience 
      Basel, University Hospital Basel, University of Basel, Switzerland; Department of 
      Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia 
      (CEMCAT), Vall d'Hebron University Hospital, Barcelona, Spain; F. Hoffmann-La 
      Roche Ltd. (L.C., C.C., R.H., H.K., N.P.), Basel, Switzerland; Genentech, Inc. 
      (A.P.), South San Francisco, CA; IQVIA Solutions Inc. (K.P.), Amsterdam, The 
      Netherlands; and Department of Neurology (J.S.W.), McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth).
FAU - Montalban, Xavier
AU  - Montalban X
AUID- ORCID: 0000-0002-0098-9918
AD  - From the Department of Neurology (S.L.H.), University of California, San 
      Francisco; Departments of Medicine, Clinical Research, Biomedicine and Biomedical 
      Engineering (L.K.), Research Center for Clinical Neuroimmunology and Neuroscience 
      Basel, University Hospital Basel, University of Basel, Switzerland; Department of 
      Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia 
      (CEMCAT), Vall d'Hebron University Hospital, Barcelona, Spain; F. Hoffmann-La 
      Roche Ltd. (L.C., C.C., R.H., H.K., N.P.), Basel, Switzerland; Genentech, Inc. 
      (A.P.), South San Francisco, CA; IQVIA Solutions Inc. (K.P.), Amsterdam, The 
      Netherlands; and Department of Neurology (J.S.W.), McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth).
FAU - Craveiro, Licinio
AU  - Craveiro L
AD  - From the Department of Neurology (S.L.H.), University of California, San 
      Francisco; Departments of Medicine, Clinical Research, Biomedicine and Biomedical 
      Engineering (L.K.), Research Center for Clinical Neuroimmunology and Neuroscience 
      Basel, University Hospital Basel, University of Basel, Switzerland; Department of 
      Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia 
      (CEMCAT), Vall d'Hebron University Hospital, Barcelona, Spain; F. Hoffmann-La 
      Roche Ltd. (L.C., C.C., R.H., H.K., N.P.), Basel, Switzerland; Genentech, Inc. 
      (A.P.), South San Francisco, CA; IQVIA Solutions Inc. (K.P.), Amsterdam, The 
      Netherlands; and Department of Neurology (J.S.W.), McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth).
FAU - Chognot, Cathy
AU  - Chognot C
AD  - From the Department of Neurology (S.L.H.), University of California, San 
      Francisco; Departments of Medicine, Clinical Research, Biomedicine and Biomedical 
      Engineering (L.K.), Research Center for Clinical Neuroimmunology and Neuroscience 
      Basel, University Hospital Basel, University of Basel, Switzerland; Department of 
      Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia 
      (CEMCAT), Vall d'Hebron University Hospital, Barcelona, Spain; F. Hoffmann-La 
      Roche Ltd. (L.C., C.C., R.H., H.K., N.P.), Basel, Switzerland; Genentech, Inc. 
      (A.P.), South San Francisco, CA; IQVIA Solutions Inc. (K.P.), Amsterdam, The 
      Netherlands; and Department of Neurology (J.S.W.), McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth).
FAU - Hughes, Richard
AU  - Hughes R
AUID- ORCID: 0000-0001-5532-406X
AD  - From the Department of Neurology (S.L.H.), University of California, San 
      Francisco; Departments of Medicine, Clinical Research, Biomedicine and Biomedical 
      Engineering (L.K.), Research Center for Clinical Neuroimmunology and Neuroscience 
      Basel, University Hospital Basel, University of Basel, Switzerland; Department of 
      Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia 
      (CEMCAT), Vall d'Hebron University Hospital, Barcelona, Spain; F. Hoffmann-La 
      Roche Ltd. (L.C., C.C., R.H., H.K., N.P.), Basel, Switzerland; Genentech, Inc. 
      (A.P.), South San Francisco, CA; IQVIA Solutions Inc. (K.P.), Amsterdam, The 
      Netherlands; and Department of Neurology (J.S.W.), McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth).
FAU - Koendgen, Harold
AU  - Koendgen H
AD  - From the Department of Neurology (S.L.H.), University of California, San 
      Francisco; Departments of Medicine, Clinical Research, Biomedicine and Biomedical 
      Engineering (L.K.), Research Center for Clinical Neuroimmunology and Neuroscience 
      Basel, University Hospital Basel, University of Basel, Switzerland; Department of 
      Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia 
      (CEMCAT), Vall d'Hebron University Hospital, Barcelona, Spain; F. Hoffmann-La 
      Roche Ltd. (L.C., C.C., R.H., H.K., N.P.), Basel, Switzerland; Genentech, Inc. 
      (A.P.), South San Francisco, CA; IQVIA Solutions Inc. (K.P.), Amsterdam, The 
      Netherlands; and Department of Neurology (J.S.W.), McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth).
FAU - Pasquarelli, Noemi
AU  - Pasquarelli N
AD  - From the Department of Neurology (S.L.H.), University of California, San 
      Francisco; Departments of Medicine, Clinical Research, Biomedicine and Biomedical 
      Engineering (L.K.), Research Center for Clinical Neuroimmunology and Neuroscience 
      Basel, University Hospital Basel, University of Basel, Switzerland; Department of 
      Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia 
      (CEMCAT), Vall d'Hebron University Hospital, Barcelona, Spain; F. Hoffmann-La 
      Roche Ltd. (L.C., C.C., R.H., H.K., N.P.), Basel, Switzerland; Genentech, Inc. 
      (A.P.), South San Francisco, CA; IQVIA Solutions Inc. (K.P.), Amsterdam, The 
      Netherlands; and Department of Neurology (J.S.W.), McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth).
FAU - Pradhan, Ashish
AU  - Pradhan A
AD  - From the Department of Neurology (S.L.H.), University of California, San 
      Francisco; Departments of Medicine, Clinical Research, Biomedicine and Biomedical 
      Engineering (L.K.), Research Center for Clinical Neuroimmunology and Neuroscience 
      Basel, University Hospital Basel, University of Basel, Switzerland; Department of 
      Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia 
      (CEMCAT), Vall d'Hebron University Hospital, Barcelona, Spain; F. Hoffmann-La 
      Roche Ltd. (L.C., C.C., R.H., H.K., N.P.), Basel, Switzerland; Genentech, Inc. 
      (A.P.), South San Francisco, CA; IQVIA Solutions Inc. (K.P.), Amsterdam, The 
      Netherlands; and Department of Neurology (J.S.W.), McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth).
FAU - Prajapati, Kalpesh
AU  - Prajapati K
AD  - From the Department of Neurology (S.L.H.), University of California, San 
      Francisco; Departments of Medicine, Clinical Research, Biomedicine and Biomedical 
      Engineering (L.K.), Research Center for Clinical Neuroimmunology and Neuroscience 
      Basel, University Hospital Basel, University of Basel, Switzerland; Department of 
      Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia 
      (CEMCAT), Vall d'Hebron University Hospital, Barcelona, Spain; F. Hoffmann-La 
      Roche Ltd. (L.C., C.C., R.H., H.K., N.P.), Basel, Switzerland; Genentech, Inc. 
      (A.P.), South San Francisco, CA; IQVIA Solutions Inc. (K.P.), Amsterdam, The 
      Netherlands; and Department of Neurology (J.S.W.), McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth).
FAU - Wolinsky, Jerry S
AU  - Wolinsky JS
AUID- ORCID: 0000-0002-8197-2762
AD  - From the Department of Neurology (S.L.H.), University of California, San 
      Francisco; Departments of Medicine, Clinical Research, Biomedicine and Biomedical 
      Engineering (L.K.), Research Center for Clinical Neuroimmunology and Neuroscience 
      Basel, University Hospital Basel, University of Basel, Switzerland; Department of 
      Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia 
      (CEMCAT), Vall d'Hebron University Hospital, Barcelona, Spain; F. Hoffmann-La 
      Roche Ltd. (L.C., C.C., R.H., H.K., N.P.), Basel, Switzerland; Genentech, Inc. 
      (A.P.), South San Francisco, CA; IQVIA Solutions Inc. (K.P.), Amsterdam, The 
      Netherlands; and Department of Neurology (J.S.W.), McGovern Medical School, The 
      University of Texas Health Science Center at Houston (UTHealth).
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210902
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - A10SJL62JY (ocrelizumab)
SB  - IM
CIN - Neurology. 2021 Oct 19;97(16):751-753. PMID: 34475129
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*adverse effects
MH  - Clinical Trials as Topic
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology/*etiology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis, Chronic Progressive/*drug therapy
MH  - Multiple Sclerosis, Relapsing-Remitting/*drug therapy
MH  - Young Adult
PMC - PMC8548959
EDAT- 2021/09/04 06:00
MHDA- 2021/10/30 06:00
PMCR- 2021/10/19
CRDT- 2021/09/03 05:58
PHST- 2021/01/15 00:00 [received]
PHST- 2021/07/29 00:00 [accepted]
PHST- 2021/09/04 06:00 [pubmed]
PHST- 2021/10/30 06:00 [medline]
PHST- 2021/09/03 05:58 [entrez]
PHST- 2021/10/19 00:00 [pmc-release]
AID - WNL.0000000000012700 [pii]
AID - NEUROLOGY2020169914 [pii]
AID - 10.1212/WNL.0000000000012700 [doi]
PST - ppublish
SO  - Neurology. 2021 Oct 19;97(16):e1546-e1559. doi: 10.1212/WNL.0000000000012700. 
      Epub 2021 Sep 2.