Abstract: P1593
Type: LB Poster
Abstract Category: Late Breaking News
Background: No Evidence of Disease Activity (NEDA) is a composite measure of the absence of detectable clinical and magnetic resonance imaging (MRI) disease activity in relapsing multiple sclerosis (RMS). However, analyses of NEDA using a re-baseline approach may more closely reflect the effects of disease-modifying treatments. Ocrelizumab (OCR; 600 mg), which demonstrated a robust effect on MRI activity at 8 weeks in a Phase II study of MS patients, was evaluated for NEDA from baseline (Week 0) and following re-baselining at the time of first MRI (Week 24).
Objective: To assess the effect of OCR on the proportion of patients with NEDA by epoch in the pooled OPERA I and II studies.
Methods: In OPERA I and II, patients were randomised 1:1 to receive OCR 600 mg every 24 weeks or IFNβ‐1a 44 µg three-times weekly for 96 weeks. NEDA [defined as the absence of protocol-defined relapses, 12-week confirmed disability progression (CDP), new/enlarging T2 lesions and T1 gadolinium-enhancing lesions] was assessed in the overall intent-to-treat population over the controlled treatment phase (baseline to 96 weeks). Further analyses evaluated the proportion of patients with NEDA from baseline to Week 48 versus from Week 48 to Week 96, and from baseline to Week 24 versus from Week 24 to Week 96. Brain MRI was undertaken at baseline and at Weeks 24, 48 and 96.
Results: In pooled analyses of OPERA I and II, the proportion of patients with NEDA was increased by 75% with OCR compared with IFNβ-1a over 96 weeks (47.7% vs 27.1%; p< 0.0001). Compared with IFNβ-1a, the proportion of patients with NEDA was 57% higher with OCR from baseline to Week 48 (53.5% vs 34.0%) and 47% higher from Week 48 to Week 96 (85.9% vs 58.6%; both p< 0.0001). Compared with IFNβ-1a, the proportion of patients with NEDA was 36% higher with OCR from baseline to Week 24 (58.3% vs 42.8%) and 76% higher from Week 24 to Week 96 (75.5% vs 42.9%; both p< 0.0001). In the OCR and IFNβ-1a groups, respectively, 79.8% vs 44.4% of patients with evidence of disease activity during Weeks 0-48 achieved NEDA during Weeks 48-96 (relative increase with OCR: 84%; p< 0.0001).
Conclusions: A higher proportion of patients reached NEDA at first MRI at Week 24 with OCR versus IFNβ-1a. After re-baselining, from Week 24 to 96 OCR treatment further increased the proportion of patients reaching NEDA status by 76%, relative to IFNβ-1a.
Sponsored by F. Hoffmann-La Roche Ltd.
Disclosure: Gavin Giovannoni has received honoraria from AbbVie, Bayer HealthCare, Biogen, Canbex Therapeutics, Five Prime Therapeutics, Genzyme, GSK, GW Pharma, Merck, Merck Serono, Novartis, Protein Discovery Laboratories, F. Hoffmann-La Roche Ltd, Synthon, Teva Neuroscience, UCB and Vertex; research grant support from Biogen, Ironwood, Merck Serono, Merz and Novartis; and compensation from Elsevier.
Douglas L. Arnold reports personal fees for consulting from Acorda, Biogen, F. Hoffmann-La Roche Ltd, MedImmune, Mitsubishi, Novartis, Receptos, Sanofi-Aventis; grants from Biogen and Novartis; and an equity interest in NeuroRx Research.
Amit Bar-Or has received personal compensation for consulting, serving on scientific advisory boards and/or speaking activities from: Bayer, Bayhill Therapeutics, Berlex, Biogen Idec, BioMS, Diogenix, Eli Lilly, Genentech, Inc, GSK, Guthy-Jackson/GGF, Merck Serono, Novartis, Ono Pharmacia, F. Hoffmann-La Roche Ltd, Sanofi, Teva Neuroscience and Wyeth.
Giancarlo Comi has received compensation for consulting services and/or speaking activities from Novartis, Teva, Sanofi, Genzyme, Merck, Biogen, Bayer, Excemed, Serono Symposia International Foundation, Almirall, Chugai and Receptos.
Hans-Peter Hartung has received honoraria for consulting, serving on steering committees and speaking at scientific symposia with approval by the Rector of Heinrich-Heine-University from Bayer, Biogen, GeNeuro, Genzyme, Merck Serono, MedImmune, Novartis, Octapharma, Opexa, F. Hoffmann-La Roche Ltd, Teva and Sanofi.
Eva Havrdová has received honoraria/research support from Biogen, Sanofi Genzyme, Merck Serono, Novartis, Roche and Teva; and participated in advisory boards for Actelion, Biogen, Sanofi Genzyme, Merck Serono, Novartis, Receptos, and Teva.
Ludwig Kappos"s institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos" activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer Health Care Pharmaceuticals, CLC Behring, Genentech, Inc, GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono Pharma, Pfizer, Receptos, F. Hoffmann-La Roche Ltd, Sanofi-Aventis, Santhera, Siemens and Teva, UCB, Xenport; royalties from Neurostatus AG; research grants from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, Novartis Research Foundation and Roche Research foundation.
Fred Lublin reports funding of research from Biogen Idec, Novartis Pharmaceuticals Corp, Teva Neuroscience, Inc, Genzyme, Sanofi, Celgene, Transparency Life Sciences, NIH and NMSS; consulting agreements/advisory boards/DSMB for Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Inc, Novartis, Teva Neuroscience, Actelion, Sanofi, Acorda, Questcor/Malinckrodt, F. Hoffmann-La Roche Ltd, Genentech, Inc, Celgene, Genzyme, MedImmune, Osmotica, Xenoport, Receptos, Forward Pharma, BBB technologies and Akros; and he is Co-chief Editor for Multiple Sclerosis and Related Diseases; and has current financial interests/stock ownership in Cognition Pharmaceuticals, Inc.
Krzysztof Selmaj has received honoraria for advisory boards from Biogen, Novartis, Teva, F. Hoffmann-La Roche Ltd, Merck, Synthon, Receptos and Genzyme.
Anthony Traboulsee has received honoraria for advisory boards from Genzyme and F. Hoffmann-La Roche Ltd. He is a steering committee member for F. Hoffmann-La Roche Ltd.
Shibeshih Belachew is an employee of F. Hoffmann-La Roche Ltd.
Jian Han is an employee and/or shareholder of Genentech, Inc.
Laura Julian is an employee and/or shareholder of Genentech, Inc.
Stephen L. Hauser serves on the scientific advisory boards for Annexon, Symbiotix and Bionure; he has also received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations.
Abstract: P1593
Type: LB Poster
Abstract Category: Late Breaking News
Background: No Evidence of Disease Activity (NEDA) is a composite measure of the absence of detectable clinical and magnetic resonance imaging (MRI) disease activity in relapsing multiple sclerosis (RMS). However, analyses of NEDA using a re-baseline approach may more closely reflect the effects of disease-modifying treatments. Ocrelizumab (OCR; 600 mg), which demonstrated a robust effect on MRI activity at 8 weeks in a Phase II study of MS patients, was evaluated for NEDA from baseline (Week 0) and following re-baselining at the time of first MRI (Week 24).
Objective: To assess the effect of OCR on the proportion of patients with NEDA by epoch in the pooled OPERA I and II studies.
Methods: In OPERA I and II, patients were randomised 1:1 to receive OCR 600 mg every 24 weeks or IFNβ‐1a 44 µg three-times weekly for 96 weeks. NEDA [defined as the absence of protocol-defined relapses, 12-week confirmed disability progression (CDP), new/enlarging T2 lesions and T1 gadolinium-enhancing lesions] was assessed in the overall intent-to-treat population over the controlled treatment phase (baseline to 96 weeks). Further analyses evaluated the proportion of patients with NEDA from baseline to Week 48 versus from Week 48 to Week 96, and from baseline to Week 24 versus from Week 24 to Week 96. Brain MRI was undertaken at baseline and at Weeks 24, 48 and 96.
Results: In pooled analyses of OPERA I and II, the proportion of patients with NEDA was increased by 75% with OCR compared with IFNβ-1a over 96 weeks (47.7% vs 27.1%; p< 0.0001). Compared with IFNβ-1a, the proportion of patients with NEDA was 57% higher with OCR from baseline to Week 48 (53.5% vs 34.0%) and 47% higher from Week 48 to Week 96 (85.9% vs 58.6%; both p< 0.0001). Compared with IFNβ-1a, the proportion of patients with NEDA was 36% higher with OCR from baseline to Week 24 (58.3% vs 42.8%) and 76% higher from Week 24 to Week 96 (75.5% vs 42.9%; both p< 0.0001). In the OCR and IFNβ-1a groups, respectively, 79.8% vs 44.4% of patients with evidence of disease activity during Weeks 0-48 achieved NEDA during Weeks 48-96 (relative increase with OCR: 84%; p< 0.0001).
Conclusions: A higher proportion of patients reached NEDA at first MRI at Week 24 with OCR versus IFNβ-1a. After re-baselining, from Week 24 to 96 OCR treatment further increased the proportion of patients reaching NEDA status by 76%, relative to IFNβ-1a.
Sponsored by F. Hoffmann-La Roche Ltd.
Disclosure: Gavin Giovannoni has received honoraria from AbbVie, Bayer HealthCare, Biogen, Canbex Therapeutics, Five Prime Therapeutics, Genzyme, GSK, GW Pharma, Merck, Merck Serono, Novartis, Protein Discovery Laboratories, F. Hoffmann-La Roche Ltd, Synthon, Teva Neuroscience, UCB and Vertex; research grant support from Biogen, Ironwood, Merck Serono, Merz and Novartis; and compensation from Elsevier.
Douglas L. Arnold reports personal fees for consulting from Acorda, Biogen, F. Hoffmann-La Roche Ltd, MedImmune, Mitsubishi, Novartis, Receptos, Sanofi-Aventis; grants from Biogen and Novartis; and an equity interest in NeuroRx Research.
Amit Bar-Or has received personal compensation for consulting, serving on scientific advisory boards and/or speaking activities from: Bayer, Bayhill Therapeutics, Berlex, Biogen Idec, BioMS, Diogenix, Eli Lilly, Genentech, Inc, GSK, Guthy-Jackson/GGF, Merck Serono, Novartis, Ono Pharmacia, F. Hoffmann-La Roche Ltd, Sanofi, Teva Neuroscience and Wyeth.
Giancarlo Comi has received compensation for consulting services and/or speaking activities from Novartis, Teva, Sanofi, Genzyme, Merck, Biogen, Bayer, Excemed, Serono Symposia International Foundation, Almirall, Chugai and Receptos.
Hans-Peter Hartung has received honoraria for consulting, serving on steering committees and speaking at scientific symposia with approval by the Rector of Heinrich-Heine-University from Bayer, Biogen, GeNeuro, Genzyme, Merck Serono, MedImmune, Novartis, Octapharma, Opexa, F. Hoffmann-La Roche Ltd, Teva and Sanofi.
Eva Havrdová has received honoraria/research support from Biogen, Sanofi Genzyme, Merck Serono, Novartis, Roche and Teva; and participated in advisory boards for Actelion, Biogen, Sanofi Genzyme, Merck Serono, Novartis, Receptos, and Teva.
Ludwig Kappos"s institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos" activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer Health Care Pharmaceuticals, CLC Behring, Genentech, Inc, GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono Pharma, Pfizer, Receptos, F. Hoffmann-La Roche Ltd, Sanofi-Aventis, Santhera, Siemens and Teva, UCB, Xenport; royalties from Neurostatus AG; research grants from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, Novartis Research Foundation and Roche Research foundation.
Fred Lublin reports funding of research from Biogen Idec, Novartis Pharmaceuticals Corp, Teva Neuroscience, Inc, Genzyme, Sanofi, Celgene, Transparency Life Sciences, NIH and NMSS; consulting agreements/advisory boards/DSMB for Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Inc, Novartis, Teva Neuroscience, Actelion, Sanofi, Acorda, Questcor/Malinckrodt, F. Hoffmann-La Roche Ltd, Genentech, Inc, Celgene, Genzyme, MedImmune, Osmotica, Xenoport, Receptos, Forward Pharma, BBB technologies and Akros; and he is Co-chief Editor for Multiple Sclerosis and Related Diseases; and has current financial interests/stock ownership in Cognition Pharmaceuticals, Inc.
Krzysztof Selmaj has received honoraria for advisory boards from Biogen, Novartis, Teva, F. Hoffmann-La Roche Ltd, Merck, Synthon, Receptos and Genzyme.
Anthony Traboulsee has received honoraria for advisory boards from Genzyme and F. Hoffmann-La Roche Ltd. He is a steering committee member for F. Hoffmann-La Roche Ltd.
Shibeshih Belachew is an employee of F. Hoffmann-La Roche Ltd.
Jian Han is an employee and/or shareholder of Genentech, Inc.
Laura Julian is an employee and/or shareholder of Genentech, Inc.
Stephen L. Hauser serves on the scientific advisory boards for Annexon, Symbiotix and Bionure; he has also received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations.