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Controlled Clinical Trial
. 2022 Apr;28(5):790-800.
doi: 10.1177/13524585211035740. Epub 2021 Aug 12.

Ocrelizumab treatment for relapsing-remitting multiple sclerosis after a suboptimal response to previous disease-modifying therapy: A nonrandomized controlled trial

Bianca Weinstock-Guttman  1 , Robert Bermel  2 , Gary Cutter  3 , Mark S Freedman  4 , Thomas P Leist  5 , Xiaoye Ma  6 , Deidre Kile  6 , Bruno Musch  6 , Anthony T Reder  7 , Jerry S Wolinsky  8
Affiliations
Controlled Clinical Trial

Ocrelizumab treatment for relapsing-remitting multiple sclerosis after a suboptimal response to previous disease-modifying therapy: A nonrandomized controlled trial

Bianca Weinstock-Guttman et al. Mult Scler. 2022 Apr.

Abstract

Background: Many patients with multiple sclerosis (MS) experience suboptimal disease control despite the use of disease-modifying therapy (DMT).

Objective: To assess the efficacy and safety of ocrelizumab (OCR) in patients with relapsing-remitting MS (RRMS) and suboptimal response to prior DMTs.

Methods: Patients with RRMS and suboptimal responses (one clinically reported relapse and/or lesion activity) after ⩾ 6 months on another DMT were enrolled. OCR 600 mg was given intravenously every 24 weeks. The primary outcome was no evidence of disease activity (NEDA), defined as the absence of protocol-defined relapse, confirmed disability progression (CDP), T1 Gd-enhancing lesions, and new/enlarging T2 lesions.

Results: The intention-to-treat (ITT) population included 608 patients; NEDA was analyzed in a modified ITT (mITT) population (n = 576 (94.7%)). Over 96 weeks, 48.1% of mITT patients achieved NEDA, and most were free from protocol-defined relapse (89.6%), CDP (89.6%), and T1 Gd-enhancing lesions (95.5%); 59.5% had no new/enlarging T2 lesions. Safety observations were consistent with findings in the pivotal trials.

Conclusion: Consistent efficacy of OCR on clinical and magnetic resonance imaging (MRI) disease activity measures and progression was shown in patients with RRMS and a suboptimal response to prior DMTs; no new safety signals were observed.

Keywords: MRI; Multiple sclerosis; disease progression; ocrelizumab; safety; switch.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: B.W.-G. has received honoraria for serving on advisory boards and educational programs from Teva Pharmaceuticals, Biogen Idec, Novartis, EMD Serono, Sanofi Genzyme, Genentech, Inc., and Celgene; and has received support for research activities from EMD Serono, Biogen Idec, Teva Neuroscience, and Novartis. R.B. has received consulting fees from Biogen, F. Hoffmann-La Roche Ltd, Genentech, Inc., Genzyme, and Novartis. G.C. has served on data and safety monitoring boards for AMO Pharmaceuticals, BioLineRx, Horizon Pharmaceuticals, Merck, Merck/Pfizer, OPKO Biologics, Neurim, Orphazyme, Sanofi-Aventis, Reata Pharmaceuticals, Receptos/Celgene, Teva Pharmaceuticals, NHLBI (protocol review committee), and NICHD (OPRU oversight committee); and has served on consulting or advisory boards for Atara Biotherapeutics, Axon, Biogen, BioTherapeutics, Argenx, BrainStorm Cell Therapeutics, Charleston Laboratories, Click Therapeutics, Genzyme, Genentech, Inc., GW Pharmaceuticals, Klein Buendel, MedImmune, MedDay, Novartis, Roche, SciFluor, Somahlution, Teva Pharmaceuticals, TG Therapeutics, and UT Houston. G.C. is employed by the University of Alabama at Birmingham and is president of Pythagoras, Inc., a private consulting company located in Birmingham, AL, USA. M.S.F. has received research or educational grants from Genzyme Canada; has received consultation fees or honoraria from Actelion, Bayer Healthcare, Biogen Idec, Chugai, Clene Nanomedicine, EMD Canada, Genzyme, Merck Serono, Novartis, F. Hoffmann-La Roche Ltd, Sanofi-Aventis, and Teva Canada Innovation; is a member of a company advisory board, board of directors or similar group for Actelion, Bayer Healthcare, Biogen Idec, Clene Nanomedicine, F. Hoffmann-La Roche Ltd, Merck Serono, MedDay, Novartis, and Sanofi-Aventis; and has participated in a company-sponsored speakers’ bureau for Sanofi Genzyme. T.P.L. has received compensation for consulting from Bayer, Biogen, EMD Serono, Genentech, Inc., Novartis, Sanofi Genzyme, and Teva Neuroscience; as a speaker from Biogen, Genentech, Inc., Novartis, Sanofi Genzyme, and Teva Neuroscience; and for research from Alkermes, Novartis, and Sun Pharma. X.M. is an employee of Genentech, Inc. D.K. is an employee of Genentech, Inc. B.M. is an employee of Genentech, Inc. and a shareholder of F. Hoffmann-La Roche Ltd. A.T.R. has, in the last year, received consulting fees from Bayer, Biogen, EMD Serono, Genentech, Inc., Genzyme, Novartis, and Mallinckrodt (formerly Questcor). J.S.W. has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from AbbVie, Actelion, Alkermes, Biogen, Bionest, Celgene, Clene Nanomedicine, EMD Serono, Forward Pharma A/S, GeNeuro, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, and Sanofi Genzyme; royalties are received for outlicensed monoclonal antibodies through UTHealth from Millipore Corporation.

Figures

Figure 1.
Figure 1.
(a) CHORDS study design and (b) CONSORT diagram. DMT: disease-modifying therapy; EDSS: Expanded Disability Status Scale; ITT: intention-to-treat; mITT: modified ITT; OCR: ocrelizumab. aAdverse events leading to study treatment discontinuation were rash (n = 1), coccidioidomycosis (n = 1), Crohn’s disease (n = 1), subdural hematoma (n = 1), mental disorder (n = 1), latent tuberculosis (n = 1), interstitial granulomatous dermatitis (n = 1), diarrhea (n = 1), and multiple sclerosis relapse (n = 1). bOther reasons for discontinuation were site closure without the patient wanting to transfer to another site (n = 6), desire to become pregnant (n = 2), incarceration (n = 1), and drug abuse (n = 1), which was exclusionary per protocol.
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