Contributions
Abstract: P654
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Ocrelizumab (OCR) showed superior efficacy vs interferon beta-1a (IFNβ1a) in the Phase III OPERA I and OPERA II trials in relapsing multiple sclerosis (RMS). Confirmed disability progression (CDP) based on a composite of the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW) and 9-hole peg test (9HPT) may better characterise aspects of disability progression, such as ambulation and hand/arm function, than EDSS alone and has improved sensitivity for assessing progression in secondary progressive multiple sclerosis (SPMS).
Objective: To assess OCR vs IFNβ1a on composite CDP independent of relapse activity (CCDP-IRA) in patients with RMS.
Methods: RMS patients, including SPMS patients with relapses, in OPERA I and OPERA II (NCT01247324/NCT01412333) received OCR 600 mg IV q24w or IFNβ1a 44 µg SC tiw over 96 weeks. CCDP was defined as disability progression measured by EDSS (increase of ≥1.0 or 0.5 if baseline >5.5) or ≥20% increase in T25FW or ≥20% increase in 9HPT confirmed after ≥12 or ≥24 weeks. For Definition 1 of CCDP-IRA the reference EDSS/T25FW/9HPT was re-baselined at first available assessment ≥30 days after each relapse and no relapse should occur between baseline and initial disability progression [IDP], as well as within 30 days after IDP and 30 days prior to IDP confirmation. Definition 2 included a period of no relapse for 30 days after IDP confirmation. A subgroup analysis included patients at potentially higher risk of SPMS based on baseline EDSS ≥4.0 and pyramidal Kurtzke Functional Systems Score ≥2.
Results: In the pooled intention-to-treat (ITT) cohort (N=1,656), the risk reduction (RR; OCR vs IFNβ1a) for 12- and 24-week CCDP was 34% (30.7% vs 21.5%; p< 0.001) and 31% (22.6% vs 16.1%; p=0.002). The 12- and 24-week CCDP-IRA RRs for Definition 1 were 24% (25.4% vs 19.6%; p=0.010) and 22% (19.2% vs 14.9%; p=0.046); and for Definition 2 were 25% (25.4% vs 19.5%; p=0.008) and 23% (19.2% vs 14.8%; p=0.039). In the subgroup at higher risk of SPMS, 12- and 24-week RRs for CCDP-IRA (Definition 2) were 40% (31.2% vs 19.1%; p=0.022) and 36% (26.9% vs 16.6%; p=0.064). All components of CCDP-IRA in the ITT and subgroups followed similar trends.
Conclusions: The results show that considerable disability progression in RMS occurs independently of protocol-defined relapses. Ocrelizumab significantly reduced this progression vs IFNβ1a in the OPERA ITT population of RMS patients and more so in the subgroup at higher risk of SPMS.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
L. Kappos's institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof. Kappos's activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer HealthCare Pharmaceuticals, CLC Behring, Genentech, Inc., GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono Pharma, Pfizer, Receptos, F. Hoffmann-La Roche Ltd, Sanofi, Santhera, Siemens, Teva, UCB and XenoPort; licence fees for Neurostatus products; and research grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto Foundation, the Novartis Research Foundation and the Roche Research Foundation.
J.S. Wolinsky has served on advisory boards, data monitoring or steering committees, or held consulting agreements from the following commercial entities: AbbVie, Alkermes, Bayer HealthCare, Biogen, Celgene, Clene Nanomedicine, Forward Pharma A/S, MedDay, Novartis, Roche/Genentech, Sanofi Genzyme, Takeda and Teva Pharmaceuticals; royalties are received for outlicensed monoclonal antibodies through UTHealth from Millipore Corporation.
G. 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.
D.L. Arnold reports 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.
F. Lublin reports funding of research from Biogen Idec, Novartis Pharmaceuticals Corporation, 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/Mallinckrodt, F. Hoffmann-La Roche Ltd, Genentech, Inc., Celgene, Genzyme, MedImmune, Osmotica, XenoPort, Receptos, Forward Pharma, BBB technologies and Akros; is co-chief editor for Multiple Sclerosis and Related Disorders; and has current financial interests/stock ownership in Cognition Pharmaceuticals, Inc.
Q. Wang is an employee of F. Hoffmann-La Roche Ltd.
F. Model is an employee of F. Hoffmann-La Roche Ltd.
W. Wei is an employee of F. Hoffmann-La Roche Ltd.
H. Garren is an employee and shareholder of Genentech, Inc.
M. Manfrini is an employee of F. Hoffmann-La Roche Ltd.
S. Belachew is an employee and shareholder of F. Hoffmann-La Roche Ltd.
S.L. Hauser serves on the board of trustees for Neurona and on 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: P654
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Ocrelizumab (OCR) showed superior efficacy vs interferon beta-1a (IFNβ1a) in the Phase III OPERA I and OPERA II trials in relapsing multiple sclerosis (RMS). Confirmed disability progression (CDP) based on a composite of the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW) and 9-hole peg test (9HPT) may better characterise aspects of disability progression, such as ambulation and hand/arm function, than EDSS alone and has improved sensitivity for assessing progression in secondary progressive multiple sclerosis (SPMS).
Objective: To assess OCR vs IFNβ1a on composite CDP independent of relapse activity (CCDP-IRA) in patients with RMS.
Methods: RMS patients, including SPMS patients with relapses, in OPERA I and OPERA II (NCT01247324/NCT01412333) received OCR 600 mg IV q24w or IFNβ1a 44 µg SC tiw over 96 weeks. CCDP was defined as disability progression measured by EDSS (increase of ≥1.0 or 0.5 if baseline >5.5) or ≥20% increase in T25FW or ≥20% increase in 9HPT confirmed after ≥12 or ≥24 weeks. For Definition 1 of CCDP-IRA the reference EDSS/T25FW/9HPT was re-baselined at first available assessment ≥30 days after each relapse and no relapse should occur between baseline and initial disability progression [IDP], as well as within 30 days after IDP and 30 days prior to IDP confirmation. Definition 2 included a period of no relapse for 30 days after IDP confirmation. A subgroup analysis included patients at potentially higher risk of SPMS based on baseline EDSS ≥4.0 and pyramidal Kurtzke Functional Systems Score ≥2.
Results: In the pooled intention-to-treat (ITT) cohort (N=1,656), the risk reduction (RR; OCR vs IFNβ1a) for 12- and 24-week CCDP was 34% (30.7% vs 21.5%; p< 0.001) and 31% (22.6% vs 16.1%; p=0.002). The 12- and 24-week CCDP-IRA RRs for Definition 1 were 24% (25.4% vs 19.6%; p=0.010) and 22% (19.2% vs 14.9%; p=0.046); and for Definition 2 were 25% (25.4% vs 19.5%; p=0.008) and 23% (19.2% vs 14.8%; p=0.039). In the subgroup at higher risk of SPMS, 12- and 24-week RRs for CCDP-IRA (Definition 2) were 40% (31.2% vs 19.1%; p=0.022) and 36% (26.9% vs 16.6%; p=0.064). All components of CCDP-IRA in the ITT and subgroups followed similar trends.
Conclusions: The results show that considerable disability progression in RMS occurs independently of protocol-defined relapses. Ocrelizumab significantly reduced this progression vs IFNβ1a in the OPERA ITT population of RMS patients and more so in the subgroup at higher risk of SPMS.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
L. Kappos's institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof. Kappos's activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer HealthCare Pharmaceuticals, CLC Behring, Genentech, Inc., GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono Pharma, Pfizer, Receptos, F. Hoffmann-La Roche Ltd, Sanofi, Santhera, Siemens, Teva, UCB and XenoPort; licence fees for Neurostatus products; and research grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto Foundation, the Novartis Research Foundation and the Roche Research Foundation.
J.S. Wolinsky has served on advisory boards, data monitoring or steering committees, or held consulting agreements from the following commercial entities: AbbVie, Alkermes, Bayer HealthCare, Biogen, Celgene, Clene Nanomedicine, Forward Pharma A/S, MedDay, Novartis, Roche/Genentech, Sanofi Genzyme, Takeda and Teva Pharmaceuticals; royalties are received for outlicensed monoclonal antibodies through UTHealth from Millipore Corporation.
G. 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.
D.L. Arnold reports 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.
F. Lublin reports funding of research from Biogen Idec, Novartis Pharmaceuticals Corporation, 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/Mallinckrodt, F. Hoffmann-La Roche Ltd, Genentech, Inc., Celgene, Genzyme, MedImmune, Osmotica, XenoPort, Receptos, Forward Pharma, BBB technologies and Akros; is co-chief editor for Multiple Sclerosis and Related Disorders; and has current financial interests/stock ownership in Cognition Pharmaceuticals, Inc.
Q. Wang is an employee of F. Hoffmann-La Roche Ltd.
F. Model is an employee of F. Hoffmann-La Roche Ltd.
W. Wei is an employee of F. Hoffmann-La Roche Ltd.
H. Garren is an employee and shareholder of Genentech, Inc.
M. Manfrini is an employee of F. Hoffmann-La Roche Ltd.
S. Belachew is an employee and shareholder of F. Hoffmann-La Roche Ltd.
S.L. Hauser serves on the board of trustees for Neurona and on 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.