Sustained reduction in confirmed disability progression in patients with primary progressive multiple sclerosis treated with ocrelizumab in the open-label extension period of the Phase III ORATORIO trial: 6.5-study year follow-up data
ECTRIMS Online Library. Wolinsky J. 09/12/19; 279457; 159
Dr. Jerry S. Wolinsky
Dr. Jerry S. Wolinsky
Contributions Biography

Abstract: 159

Type: Scientific Session

Abstract Category: Therapy - Long-term treatment monitoring

J.S. Wolinsky1, B. Brochet2, H.-P. Hartung3, R.T. Naismith4, L. Airas5, K. Coutant6, H. Koendgen6, M. Manfrini6, L. Mehta7, K. Prajapati8, L. Kappos9

1McGovern Medical School, Houston, TX, United States, 2University of Bordeaux, Bordeaux, France, 3Center of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany, 4Washington University School of Medicine, St. Louis, MO, United States, 5University of Turku, Division of Clinical Neurosciences, Finland, 6F. Hoffmann-La Roche Ltd, Basel, Switzerland, 7Genentech, Inc., South San Francisco, CA, United States, 8GCE Solutions Inc., Amsterdam, The Netherlands, 9University Hospital Basel, Basel, Switzerland

Background: The efficacy and safety of ocrelizumab (OCR) in primary progressive multiple sclerosis were demonstrated vs placebo (PBO) in the Phase III ORATORIO study (NCT01194570).
Objective: To assess the effect of switching to or earlier initiation of OCR therapy on confirmed disability progression (CDP) for at least 24 weeks, in the open-label extension (OLE) of ORATORIO.
Methods: In the ORATORIO double-blind period (DBP), patients (N=732) were randomised (2:1) to OCR or PBO and followed for ≥120 weeks until a prespecified number of CDP events occurred. At the end of the DBP, patients remained on blinded treatment until the trial outcome was ascertained (extended controlled period). At the start of the OLE, patients continued (OCR-OCR) or switched from PBO to OCR (PBO-OCR). By Week 240 the last patient had entered the OLE. Time to onset of 12- and 24-week-CDP (increase from baseline [BL] Expanded Disability Status Scale [CDP-EDSS] score of ≥1 point if BL EDSS ≤5.5 or ≥0.5 points if BL EDSS >5.5) and time to 24-week CDP on the 9-Hole Peg Test (CDP-9HPT; ≥20% increase from BL in the timed 9HPT) were analysed up to Week 312 (all patients had ~3 study years of OLE follow-up).
Results: Overall, 72% of patients entered the OLE. In the DBP, compared with PBO, OCR reduced the risk of 24-week CDP by 25% (p=0.037) and 24-week CDP-9HPT by 45% (p< 0.001). At Week 168 (12 weeks after the first patients entered the OLE), the proportion of patients with 24-week CDP-EDSS in the PBO-OCR and OCR-OCR groups was 44.7% vs 33.3% (Δ=11.4%; p=0.005), respectively. At Weeks 192, 264 and 312, the corresponding proportions were 49.3% vs 37.8% (Δ=11.5%; p=0.006), 58.7% vs 48.0% (Δ=10.7%; p=0.011) and 64.8% vs 51.7% (Δ13.1%; p=0.002). At Week 168, the proportion of patients with 24-week CDP-9HPT in the PBO-OCR and OCR-OCR groups was 29.7% vs 17.9%, respectively (Δ=11.8%; p=0.001). At Weeks 192, 264 and 312, the corresponding proportions were 32.5% vs 21.6% (Δ=10.9%; p=0.005), 39.4% vs 26.9% (Δ=12.5%; p=0.003) and 43.1% vs 30.6% (Δ12.5%; p=0.004). The safety profile observed in the OLE was generally consistent with that seen during the DBP.
Conclusions: After 6.5 study years (312 weeks) of follow-up, the proportion of patients with CDP-EDSS and CDP-9HPT was lower in patients who initiated OCR treatment earlier compared with patients initially receiving PBO; patients initiating OCR 3-5 study years (144-240 weeks) earlier accrued less disability progression compared with patients switching from PBO.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Articulate Science, UK.
J. S. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking or other activities with AbbVie, Actelion, Alkermes, Brainstorm Cell Therapeutics, Biogen, Bionest, Celgene, Clene Nanomedicine, EMD Serono, Forward Pharma A/S, GeNeuro, GW Pharma Ltd, MedDay Pharmaceuticals, Otsuka, PTC Therapeutics, Novartis, Roche/Genentech and Sanofi Genzyme; royalties are received for outlicensed monoclonal antibodies through UTHealth from Millipore Corporation.
B. Brochet reports personal fees and non-financial support from Biogen-Idec and Novartis; has received grants from Merck Serono and Bayer; has received grants and non-financial support from Genzyme and F. Hoffmann-La Roche Ltd; has received non-financial support from Teva; and has received non-financial support from Mylan.
H.-P. Hartung has received honoraria for consulting, serving on steering committees and speaking at scientific symposia with approval from the Rector of Heinrich Heine University Düsseldorf from Bayer, Biogen, Celgene, F. Hoffmann-La Roche Ltd, GeNeuro SA, Genzyme, MedImmune, Merck, Novartis, Octapharma, Receptos, Teva and Sanofi.
R. T. Naismith reports financial relationships with Alkermes, Biogen, Celgene, EMD Serono, Genentech, Inc., Genzyme, Novartis and TG Therapeutics.
L. Airas has received honoraria from Biogen, F. Hoffmann-La Roche Ltd, Genzyme, Merck Serono and Teva, and institutional research grant support from Biogen, Genzyme, Merck Serono and Novartis.
K. Coutant is an employee of F. Hoffmann-La Roche Ltd.
H. Koendgen is an employee and shareholder of F. Hoffmann-La Roche Ltd.
M. Manfrini is an employee of F. Hoffmann-La Roche Ltd.
L. Mehta is an employee of Genentech, Inc.
K. Prajapati has received consulting fees from F. Hoffmann-La Roche for statistical assistance, and is an employee of GCE Solutions Inc.
L. Kappos's institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, F. Hoffmann-La Roche Ltd, Sanofi Aventis, Santhera, Teva, Vianex and licence fees for Neurostatus-UHB products; the Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, Innoswiss, the European Union and Roche Research Foundations.

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