Evidence map›Paper›PMID 34475123›Full record

ArticleNeurology2021

Safety of Ocrelizumab in Patients With Relapsing and Primary Progressive Multiple Sclerosis.

Stephen L Hauser, Ludwig Kappos, Xavier Montalban, Licinio Craveiro, Cathy Chognot, Richard Hughes, Harold Koendgen, Noemi Pasquarelli, Ashish Pradhan, Kalpesh Prajapati and 1 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 3 pooled it
9.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

96 citing papers in PubMed, 3 syntheses or guidelines pooled it, 170 citations in OpenAlex.

  1. Pooled it
  2. Systematic literature review of immunoglobulin trends for anti-CD20 monoclonal antibodies in multiple sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023
    Pooled it
  3. Ocrelizumab for multiple sclerosis.The Cochrane database of systematic reviews · 2022
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36 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 3 countries.

Stephen L HauserFrom 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.ORCID 0000-0002-4932-4001
Ludwig KapposFrom 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).ORCID 0000-0003-4175-5509
Xavier MontalbanFrom 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).ORCID 0000-0002-0098-9918
Licinio CraveiroFrom 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).
Cathy ChognotFrom 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).
Richard HughesFrom 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).ORCID 0000-0001-5532-406X
Harold KoendgenFrom 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).
Noemi PasquarelliFrom 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).
Ashish PradhanFrom 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).
Kalpesh PrajapatiFrom 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).
Jerry S WolinskyFrom 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).ORCID 0000-0002-8197-2762
Roche (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesTo 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.

methodsSafety 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.

resultsAt 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.

Indexed as

AdolescentAdultAgedAntibodies, Monoclonal, HumanizedClinical Trials as TopicDrug-Related Side Effects and Adverse ReactionsFemaleHumansMaleMiddle AgedMultiple Sclerosis, Chronic ProgressiveMultiple Sclerosis, Relapsing-RemittingYoung AdultAntibodies, Monoclonal, Humanizedocrelizumab

Identifiers

PMID34475123
PMCPMC8548959
OpenAlexW3198774415

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.