Contributions
Abstract: P547
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: In OPERA I and II ocrelizumab (OCR) reduced the risk of 12- and 24-week confirmed disability progression (CDP) vs interferon (IFN) β1a. CDP may result either from relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA).
Objective: To report the risk of RAW and PIRA events in a pooled analysis of the OPERA I and OPERA II studies.
Methods: Patients with relapsing multiple sclerosis (RMS) from the OPERA I and OPERA II studies (NCT01247324; NCT01412333) were randomised 1:1 to receive intravenous OCR 600mg every 24 weeks (N=827) or subcutaneous IFN β1a 44µg three times weekly (N=829) for 96 weeks. RAW events were defined as a disability change occurring ≤90 days after onset of a protocol-defined relapse. RAW in Expanded Disability Status Scale (EDSS) was defined as increase in EDSS score of ≥1.0 if baseline EDSS score ≤5.5 or ≥0.5 if baseline EDSS score >5.5; composite RAW was defined as RAW in EDSS or ≥20% increase in Timed 25-Foot Walk or 9-Hole Peg Test. Composite CDP and composite PIRA were previously defined and reported. Analyses were performed on the pooled intent-to-treat population of OPERA I and II. Hazard ratios were calculated by Cox regression and p-values by log-rank test, stratified by study, region and baseline EDSS score.
Results: OCR vs IFNβ1a reduced the relative risk of 12/24-week confirmed RAW in EDSS by 59% (IFNβ1a/OCR events, n [%], 34 [4.1]/16 [1.9]; p=0.003) and 66% (IFNβ1a/OCR events, n [%], 30 [3.6]/11 [1.3]; p=0.002]), respectively; reductions in 12/24-week confirmed composite RAW were 55% (IFNβ1a/OCR events, n [%], 37 [4.5]/19 [2.3]; p=0.004) and 58% (IFNβ1a/OCR events, n [%], 27 [3.3]/12 [1.5]; p=0.009), respectively. A large majority of overall disability accumulation corresponded to PIRA events (82.3/84.5% of 12/24-week confirmed composite CDP events). Defined events of RAW and PIRA appeared to be mostly non-overlapping (only 1.5/1.3% of patients with 12/24-week confirmed composite CDP events experienced both RAW and PIRA).
Conclusions: Ocrelizumab was superior to IFNβ1a in preventing confirmed accumulation of disability. Our results indicate that a considerable proportion of overall accumulation in disability in a typical RMS population might be related to an underlying progressive course, thus challenging the current phenotypical distinction of relapsing and progressive forms of the disease.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
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.
J. S. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Acetilon, Alkermes, Biogen, Bionest, Celgene, Clene Nanomedicine, EMD Serono, Forward Pharma A/S, GeNeuro, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, Sanofi Genzyme.; royalties are received for out-licensed 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 Pharmaceuticals, Merck, Merck Serono, Novartis, Protein Discovery Laboratories, F. Hoffmann-La Roche Ltd, Synthon, Teva, 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.
Q. Wang is an employee of F. Hoffmann-La Roche Ltd.
C. Bernasconi is a contractor for F. Hoffmann-La Roche Ltd.
F. Model is an employee of F. Hoffmann-La Roche Ltd.
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: P547
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: In OPERA I and II ocrelizumab (OCR) reduced the risk of 12- and 24-week confirmed disability progression (CDP) vs interferon (IFN) β1a. CDP may result either from relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA).
Objective: To report the risk of RAW and PIRA events in a pooled analysis of the OPERA I and OPERA II studies.
Methods: Patients with relapsing multiple sclerosis (RMS) from the OPERA I and OPERA II studies (NCT01247324; NCT01412333) were randomised 1:1 to receive intravenous OCR 600mg every 24 weeks (N=827) or subcutaneous IFN β1a 44µg three times weekly (N=829) for 96 weeks. RAW events were defined as a disability change occurring ≤90 days after onset of a protocol-defined relapse. RAW in Expanded Disability Status Scale (EDSS) was defined as increase in EDSS score of ≥1.0 if baseline EDSS score ≤5.5 or ≥0.5 if baseline EDSS score >5.5; composite RAW was defined as RAW in EDSS or ≥20% increase in Timed 25-Foot Walk or 9-Hole Peg Test. Composite CDP and composite PIRA were previously defined and reported. Analyses were performed on the pooled intent-to-treat population of OPERA I and II. Hazard ratios were calculated by Cox regression and p-values by log-rank test, stratified by study, region and baseline EDSS score.
Results: OCR vs IFNβ1a reduced the relative risk of 12/24-week confirmed RAW in EDSS by 59% (IFNβ1a/OCR events, n [%], 34 [4.1]/16 [1.9]; p=0.003) and 66% (IFNβ1a/OCR events, n [%], 30 [3.6]/11 [1.3]; p=0.002]), respectively; reductions in 12/24-week confirmed composite RAW were 55% (IFNβ1a/OCR events, n [%], 37 [4.5]/19 [2.3]; p=0.004) and 58% (IFNβ1a/OCR events, n [%], 27 [3.3]/12 [1.5]; p=0.009), respectively. A large majority of overall disability accumulation corresponded to PIRA events (82.3/84.5% of 12/24-week confirmed composite CDP events). Defined events of RAW and PIRA appeared to be mostly non-overlapping (only 1.5/1.3% of patients with 12/24-week confirmed composite CDP events experienced both RAW and PIRA).
Conclusions: Ocrelizumab was superior to IFNβ1a in preventing confirmed accumulation of disability. Our results indicate that a considerable proportion of overall accumulation in disability in a typical RMS population might be related to an underlying progressive course, thus challenging the current phenotypical distinction of relapsing and progressive forms of the disease.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
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.
J. S. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Acetilon, Alkermes, Biogen, Bionest, Celgene, Clene Nanomedicine, EMD Serono, Forward Pharma A/S, GeNeuro, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, Sanofi Genzyme.; royalties are received for out-licensed 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 Pharmaceuticals, Merck, Merck Serono, Novartis, Protein Discovery Laboratories, F. Hoffmann-La Roche Ltd, Synthon, Teva, 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.
Q. Wang is an employee of F. Hoffmann-La Roche Ltd.
C. Bernasconi is a contractor for F. Hoffmann-La Roche Ltd.
F. Model is an employee of F. Hoffmann-La Roche Ltd.
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.