Abstract: P588
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Background: The efficacy and safety of ocrelizumab (OCR) in relapsing multiple sclerosis (RMS) were demonstrated in the 96-week double-blind control period (DBP) of OPERA I and OPERA II (NCT01247324; NCT01412333). Long-term brain tissue preservation is a critical objective in the treatment of multiple sclerosis (MS).
Objective: To assess brain MRI measures of disease activity and atrophy after earlier vs delayed initiation of OCR at 5 years from core study baseline in Phase III trials in RMS.
Methods: At end of DBP (Year 2), patients entered the open-label extension (OLE) and continued OCR (OCR-OCR) or were switched from interferon (IFN) β1a to OCR (IFN-OCR) and were analysed until Year 5. Brain MRI lesion activity (T1 gadolinium-enhancing [T1Gd+] lesions, new/enlarging T2 [N/ET2] lesions) and percentage change in whole brain volume (WBV), cortical grey matter volume (cGMV) and white matter volume (WMV) were analysed.
Results: Among IFN-OCR patients, the adjusted number of T1Gd+ lesions was 0.48 lesions/scan at Week 96 (DBP Year 2), and decreased to an unadjusted rate of 0.007, 0.004 and 0.004 at Week 144 (Year 3/OCR Year 1), Week 192 (Year 4/OCR Year 2) and Week 240 (Year 5/OCR Year 3), respectively. Similarly, the number of N/ET2 lesions decreased from an adjusted rate of 2.16 lesions/scan in Year 2 pre-switch to 0.33 in Year 3 (OCR Year 1) and decreased further to unadjusted rates of 0.063 and 0.038 in Years 4 and 5 (OCR Years 2 and 3). OCR-OCR continuers maintained low numbers of T1Gd+ and N/ET2 lesions at Years 3, 4 and 5 of OCR treatment. Earlier OCR-treated patients (5 years of OCR) vs delayed IFN-OCR switchers (3 years of OCR) had lower brain atrophy from core study baseline to the end of Years 3, 4 and 5 measured by WBV change (-1.31%/-1.51%, -1.58%/-1.87% and -1.87%/-2.15%; p< 0.01 for all); cGMV change (-1.47%/-1.56%, -1.73%/-1.91% and -2.02%/-2.25%; p=0.16, p< 0.01 and p< 0.01) and WMV change (-0.94%/-1.23%, -1.11%/-1.45% and -1.33%/-1.62%; p< 0.01 for all).
Conclusions: Patients with RMS switching at Year 2 from IFN to OCR had an almost complete and sustained suppression of MRI disease activity as measured by T1Gd+ lesions and N/ET2 lesions from Year 2 to 5. At 5 years from core study baseline, patients with 5-years' continuous OCR treatment from randomisation experienced a lower brain atrophy as measured by change from baseline in whole brain, white matter and cortical grey matter volume compared with patients with a 2-year delayed OCR treatment start.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Articulate Science, UK.
D. L. Arnold has received personal fees for consulting from Acorda, Biogen, F. Hoffmann-La Roche Ltd, MedImmune, Mitsubishi, Novartis, Receptos and Sanofi-Aventis; grants from Biogen and Novartis; and an equity interest in NeuroRx Research.
L. Kappos' 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, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties 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, the European Union and Roche Research Foundations.
S. L. Hauser serves on the board of trustees for Neurona and on scientific advisory boards for Annexon, Bionure and Symbiotix and has received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations.
X. Montalban has received speaker honoraria and travel expense reimbursement for participation in scientific meetings, been a steering committee member of clinical trials or served on advisory boards of clinical trials for Actelion, Biogen, Celgene, Merck, Novartis, Oryzon, Roche, Sanofi Genzyme and Teva Pharmaceutical.
A. Traboulsee has received research support from Sanofi Genzyme, Roche, Chugai, Novartis and Biogen; has received consulting fees from Sanofi Genzyme, Roche, Teva Neuroscience, Novartis, Biogen and EMD Serono; and has received honoraria for his involvement in speaker bureau activities for Sanofi Genzyme and Teva Neuroscience.
J. S. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking or other activities with 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 out-licensed monoclonal antibodies through UTHealth from Millipore Corporation.
M. Manfrini is an employee of F. Hoffmann-La Roche Ltd.
V. Levesque is an employee of Genentech, Inc.
P. Villoslada is an employee of Genentech, Inc.
S. Belachew is an employee and shareholder of F. Hoffmann-La Roche Ltd.
F. Model is an employee of F. Hoffmann-La Roche Ltd.
S. Hubeaux is an employee and shareholder of F. Hoffmann-La Roche Ltd.
A. Bar-Or has served on scientific advisory boards for Biogen, F. Hoffmann-La Roche Ltd and Genentech, Inc., GlaxoSmithKline, Guthy-Jackson/GGF, MedImmune, Merck/EMD Serono, Mitsubishi Tanabe, Ono, Receptos and Sanofi Genzyme and has received research support from Biogen, Novartis and Sanofi Genzyme.
Abstract: P588
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Background: The efficacy and safety of ocrelizumab (OCR) in relapsing multiple sclerosis (RMS) were demonstrated in the 96-week double-blind control period (DBP) of OPERA I and OPERA II (NCT01247324; NCT01412333). Long-term brain tissue preservation is a critical objective in the treatment of multiple sclerosis (MS).
Objective: To assess brain MRI measures of disease activity and atrophy after earlier vs delayed initiation of OCR at 5 years from core study baseline in Phase III trials in RMS.
Methods: At end of DBP (Year 2), patients entered the open-label extension (OLE) and continued OCR (OCR-OCR) or were switched from interferon (IFN) β1a to OCR (IFN-OCR) and were analysed until Year 5. Brain MRI lesion activity (T1 gadolinium-enhancing [T1Gd+] lesions, new/enlarging T2 [N/ET2] lesions) and percentage change in whole brain volume (WBV), cortical grey matter volume (cGMV) and white matter volume (WMV) were analysed.
Results: Among IFN-OCR patients, the adjusted number of T1Gd+ lesions was 0.48 lesions/scan at Week 96 (DBP Year 2), and decreased to an unadjusted rate of 0.007, 0.004 and 0.004 at Week 144 (Year 3/OCR Year 1), Week 192 (Year 4/OCR Year 2) and Week 240 (Year 5/OCR Year 3), respectively. Similarly, the number of N/ET2 lesions decreased from an adjusted rate of 2.16 lesions/scan in Year 2 pre-switch to 0.33 in Year 3 (OCR Year 1) and decreased further to unadjusted rates of 0.063 and 0.038 in Years 4 and 5 (OCR Years 2 and 3). OCR-OCR continuers maintained low numbers of T1Gd+ and N/ET2 lesions at Years 3, 4 and 5 of OCR treatment. Earlier OCR-treated patients (5 years of OCR) vs delayed IFN-OCR switchers (3 years of OCR) had lower brain atrophy from core study baseline to the end of Years 3, 4 and 5 measured by WBV change (-1.31%/-1.51%, -1.58%/-1.87% and -1.87%/-2.15%; p< 0.01 for all); cGMV change (-1.47%/-1.56%, -1.73%/-1.91% and -2.02%/-2.25%; p=0.16, p< 0.01 and p< 0.01) and WMV change (-0.94%/-1.23%, -1.11%/-1.45% and -1.33%/-1.62%; p< 0.01 for all).
Conclusions: Patients with RMS switching at Year 2 from IFN to OCR had an almost complete and sustained suppression of MRI disease activity as measured by T1Gd+ lesions and N/ET2 lesions from Year 2 to 5. At 5 years from core study baseline, patients with 5-years' continuous OCR treatment from randomisation experienced a lower brain atrophy as measured by change from baseline in whole brain, white matter and cortical grey matter volume compared with patients with a 2-year delayed OCR treatment start.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Articulate Science, UK.
D. L. Arnold has received personal fees for consulting from Acorda, Biogen, F. Hoffmann-La Roche Ltd, MedImmune, Mitsubishi, Novartis, Receptos and Sanofi-Aventis; grants from Biogen and Novartis; and an equity interest in NeuroRx Research.
L. Kappos' 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, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties 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, the European Union and Roche Research Foundations.
S. L. Hauser serves on the board of trustees for Neurona and on scientific advisory boards for Annexon, Bionure and Symbiotix and has received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations.
X. Montalban has received speaker honoraria and travel expense reimbursement for participation in scientific meetings, been a steering committee member of clinical trials or served on advisory boards of clinical trials for Actelion, Biogen, Celgene, Merck, Novartis, Oryzon, Roche, Sanofi Genzyme and Teva Pharmaceutical.
A. Traboulsee has received research support from Sanofi Genzyme, Roche, Chugai, Novartis and Biogen; has received consulting fees from Sanofi Genzyme, Roche, Teva Neuroscience, Novartis, Biogen and EMD Serono; and has received honoraria for his involvement in speaker bureau activities for Sanofi Genzyme and Teva Neuroscience.
J. S. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking or other activities with 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 out-licensed monoclonal antibodies through UTHealth from Millipore Corporation.
M. Manfrini is an employee of F. Hoffmann-La Roche Ltd.
V. Levesque is an employee of Genentech, Inc.
P. Villoslada is an employee of Genentech, Inc.
S. Belachew is an employee and shareholder of F. Hoffmann-La Roche Ltd.
F. Model is an employee of F. Hoffmann-La Roche Ltd.
S. Hubeaux is an employee and shareholder of F. Hoffmann-La Roche Ltd.
A. Bar-Or has served on scientific advisory boards for Biogen, F. Hoffmann-La Roche Ltd and Genentech, Inc., GlaxoSmithKline, Guthy-Jackson/GGF, MedImmune, Merck/EMD Serono, Mitsubishi Tanabe, Ono, Receptos and Sanofi Genzyme and has received research support from Biogen, Novartis and Sanofi Genzyme.