Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial

Edward J Fox; Clyde Markowitz; Angela Applebee; Xavier Montalban; Jerry S Wolinsky; Shibeshih Belachew; Damian Fiore; Jinglan Pei; Bruno Musch; Gavin Giovannoni

doi:10.1177/1352458518808189

Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial

Mult Scler. 2018 Dec;24(14):1862-1870. doi: 10.1177/1352458518808189. Epub 2018 Nov 12.

Authors

Affiliations

¹ Central Texas Neurology Consultants and Dell Medical School, The University of Texas at Austin, Round Rock, TX, USA.
² Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³ Department of Neurology, St. Peter's Health Partners, Albany, NY, USA.
⁴ Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada/ Department of Neurology/Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (CEMCAT), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
⁵ McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
⁶ F. Hoffmann-La Roche Ltd, Basel, Switzerland.
⁷ Genentech, Inc., South San Francisco, CA, USA.
⁸ Department of Neurology, Queen Mary University of London, London, UK.

Abstract

Background: Upper extremity (UE) impairment is common with primary progressive multiple sclerosis (PPMS).

Objective: This exploratory analysis examined the effects of ocrelizumab on confirmed progression (CP) and confirmed improvement (CI) in UE impairment in patients from ORATORIO.

Methods: Patients with PPMS received ocrelizumab 600 mg or placebo every 24 weeks for ⩾120 weeks. The Nine-Hole Peg Test (9HPT) was administered at baseline (BL) and every 12 weeks thereafter. Prespecified exploratory endpoints included change in 9HPT time and proportion of patients with CP of ⩾20% in 9HPT. Analysis populations included intention-to-treat (ITT) patients and subgroups stratified by BL 9HPT time and Expanded Disability Status Scale. Post hoc analyses included the proportion of patients achieving more severe thresholds of CP and the proportion achieving CI in 9HPT.

Results: Among ITT patients, ocrelizumab significantly reduced the change in 9HPT time over 120 weeks, the risk of CP of ⩾20% in 9HPT time for both hands and the risk of more severe 9HPT progression versus placebo. Numerical trends also favoured ocrelizumab versus placebo with respect to achieving CI. Consistent directional trends were observed in subgroup analyses.

Conclusion: Ocrelizumab reduces the risk of UE disability progression and may increase the possibility of improvement versus placebo in PPMS.

Trial registration: ClinicalTrials.gov NCT01194570.

Keywords: Multiple sclerosis; disease progression; disease-modifying therapies; ocrelizumab; progressive; upper extremity impairment.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Monoclonal, Humanized / therapeutic use*
Disease Progression
Double-Blind Method
Female
Hand / physiopathology*
Humans
Infusions, Intravenous / methods
Male
Middle Aged
Multiple Sclerosis, Chronic Progressive / drug therapy*
Treatment Outcome
Upper Extremity / physiopathology*

Substances

Antibodies, Monoclonal, Humanized
ocrelizumab

Associated data

ClinicalTrials.gov/NCT01194570