Contributions
Abstract: P687
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Ocrelizumab (OCR) is an FDA-approved, humanised, CD20+ B cell-selective monoclonal antibody for the treatment of relapsing (RMS) or primary progressive forms of multiple sclerosis (PPMS). In the identical Phase III OPERA I (NCT01247324) and OPERA II studies (NCT014112333), OCR reduced annualised relapse rate (ARR; primary outcome) in patients with RMS relative to interferon β-1a (IFNβ1a) in both individual study analyses and a prespecified pooled analysis.
Objective: To assess the effect of OCR vs IFNβ1a on ARR in subgroups of the pooled OPERA studies.
Methods: In the OPERA trials, patients were randomised 1:1 to receive intravenous OCR 600 mg every 24 weeks or subcutaneous IFNβ1a 44 µg three times weekly for 96 weeks. In this post hoc analysis, ARR estimates were calculated within subgroups for the intent-to-treat population of the pooled OPERA studies (OCR, n=827; IFNβ1a, n=829) using the negative binomial or quasi-Poisson model, and the log-transformed exposure time as an offset variable (p values relate to the ARR of OCR vs IFNβ1a).
Results: Patient numbers and characteristics were comparable between treatments and within each subgroup stratum. The reduction in ARR with OCR (ARR, 0.16) vs IFNβ1a (ARR, 0.29) in the overall pooled population (p< 0.001) was maintained across all subgroups and strata; however, variations in the magnitude of effect with OCR vs IFNβ1a were seen. Results by subgroup were as follows: age
(< 40 years: OCR 0.15, IFNβ1a 0.36, p< 0.001; ≥40 years: OCR 0.17, IFNβ1a 0.23, p=0.073), gender (male: OCR 0.14, IFNβ1a 0.25, p=0.001; female: OCR 0.16, IFNβ1a 0.30, p< 0.001), prior disease-modifying therapy use in the last 2 years (yes: OCR 0.15, IFNβ1a 0.32, p< 0.001; no: OCR 0.16, IFNβ1a 0.28, p< 0.001), baseline Expanded Disability Status Scale (EDSS) score < 2.5/≥2.5 (< 2.5: OCR 0.10, IFNβ1a 0.21, p< 0.001; ≥2.5: OCR 0.16, IFNβ1a 0.29, p< 0.001), baseline EDSS score < 4.0/≥4.0
(< 4.0: OCR 0.11, IFNβ1a 0.21, p< 0.001; ≥4.0: OCR 0.11, IFNβ1a 0.22, p< 0.001), prior relapses in the last 12 months (≤1: OCR 0.14, IFNβ1a 0.24, p< 0.001; ≥2: OCR 0.20, IFNβ1a 0.38, p< 0.001) and T1 Gd+ lesions at baseline (none: OCR 0.18, IFNβ1a 0.25, p=0.025; ≥1: OCR 0.13, IFNβ1a 0.35, p< 0.001).
Conclusions: The results of these subgroup analyses were consistent with those of the overall pooled population for OCR vs IFNβ1a in reducing ARR across all subgroups considered, including demographic, clinical and MRI characteristics, in patients with RMS.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
C. Papeix has received speaking honoraria and travel expense reimbursement for participation in scientific meetings, and has participated in advisory boards in the past years with Biogen, MedDay, Merck Serono, Novartis, Roche, Sanofi Genzyme and Teva.
B. Cree has received personal compensation for consulting from AbbVie, Biogen, EMD Serono and Novartis.
B. Turner has received honoraria, travel grants and been a member of advisory boards for Biogen, Merck Serono, Novartis, Sanofi Genzyme and Roche.
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; license 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.
X. Montalban has received speaking honoraria and travel expense reimbursement for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Almirall, Bayer, Biogen, Genzyme, Merck, Novartis, Octapharma, Receptos, F. Hoffmann-La Roche Ltd, Sanofi, Teva and Trophos.
J.S. Wolinsky has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria from the following entities: AbbVie, Academic CME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, MedDay Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals and WebMD; royalties are received for outlicensed monoclonal antibodies through UTHealth from Millipore Corporation.
R. Buffels is an employee of F. Hoffmann-La Roche Ltd.
H. Garren is an employee and shareholder of Genentech, Inc.
C.J. Guittari is an employee of Genentech, Inc.
J. Han is an employee of Genentech, Inc.
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: P687
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Ocrelizumab (OCR) is an FDA-approved, humanised, CD20+ B cell-selective monoclonal antibody for the treatment of relapsing (RMS) or primary progressive forms of multiple sclerosis (PPMS). In the identical Phase III OPERA I (NCT01247324) and OPERA II studies (NCT014112333), OCR reduced annualised relapse rate (ARR; primary outcome) in patients with RMS relative to interferon β-1a (IFNβ1a) in both individual study analyses and a prespecified pooled analysis.
Objective: To assess the effect of OCR vs IFNβ1a on ARR in subgroups of the pooled OPERA studies.
Methods: In the OPERA trials, patients were randomised 1:1 to receive intravenous OCR 600 mg every 24 weeks or subcutaneous IFNβ1a 44 µg three times weekly for 96 weeks. In this post hoc analysis, ARR estimates were calculated within subgroups for the intent-to-treat population of the pooled OPERA studies (OCR, n=827; IFNβ1a, n=829) using the negative binomial or quasi-Poisson model, and the log-transformed exposure time as an offset variable (p values relate to the ARR of OCR vs IFNβ1a).
Results: Patient numbers and characteristics were comparable between treatments and within each subgroup stratum. The reduction in ARR with OCR (ARR, 0.16) vs IFNβ1a (ARR, 0.29) in the overall pooled population (p< 0.001) was maintained across all subgroups and strata; however, variations in the magnitude of effect with OCR vs IFNβ1a were seen. Results by subgroup were as follows: age
(< 40 years: OCR 0.15, IFNβ1a 0.36, p< 0.001; ≥40 years: OCR 0.17, IFNβ1a 0.23, p=0.073), gender (male: OCR 0.14, IFNβ1a 0.25, p=0.001; female: OCR 0.16, IFNβ1a 0.30, p< 0.001), prior disease-modifying therapy use in the last 2 years (yes: OCR 0.15, IFNβ1a 0.32, p< 0.001; no: OCR 0.16, IFNβ1a 0.28, p< 0.001), baseline Expanded Disability Status Scale (EDSS) score < 2.5/≥2.5 (< 2.5: OCR 0.10, IFNβ1a 0.21, p< 0.001; ≥2.5: OCR 0.16, IFNβ1a 0.29, p< 0.001), baseline EDSS score < 4.0/≥4.0
(< 4.0: OCR 0.11, IFNβ1a 0.21, p< 0.001; ≥4.0: OCR 0.11, IFNβ1a 0.22, p< 0.001), prior relapses in the last 12 months (≤1: OCR 0.14, IFNβ1a 0.24, p< 0.001; ≥2: OCR 0.20, IFNβ1a 0.38, p< 0.001) and T1 Gd+ lesions at baseline (none: OCR 0.18, IFNβ1a 0.25, p=0.025; ≥1: OCR 0.13, IFNβ1a 0.35, p< 0.001).
Conclusions: The results of these subgroup analyses were consistent with those of the overall pooled population for OCR vs IFNβ1a in reducing ARR across all subgroups considered, including demographic, clinical and MRI characteristics, in patients with RMS.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
C. Papeix has received speaking honoraria and travel expense reimbursement for participation in scientific meetings, and has participated in advisory boards in the past years with Biogen, MedDay, Merck Serono, Novartis, Roche, Sanofi Genzyme and Teva.
B. Cree has received personal compensation for consulting from AbbVie, Biogen, EMD Serono and Novartis.
B. Turner has received honoraria, travel grants and been a member of advisory boards for Biogen, Merck Serono, Novartis, Sanofi Genzyme and Roche.
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; license 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.
X. Montalban has received speaking honoraria and travel expense reimbursement for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Almirall, Bayer, Biogen, Genzyme, Merck, Novartis, Octapharma, Receptos, F. Hoffmann-La Roche Ltd, Sanofi, Teva and Trophos.
J.S. Wolinsky has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria from the following entities: AbbVie, Academic CME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, MedDay Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals and WebMD; royalties are received for outlicensed monoclonal antibodies through UTHealth from Millipore Corporation.
R. Buffels is an employee of F. Hoffmann-La Roche Ltd.
H. Garren is an employee and shareholder of Genentech, Inc.
C.J. Guittari is an employee of Genentech, Inc.
J. Han is an employee of Genentech, Inc.
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.