Contributions
Abstract: P688
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Ocrelizumab (OCR), a humanised, CD20+ B cell-selective monoclonal antibody, increased the proportion of patients with relapsing MS (RMS) with no evidence of disease activity (NEDA) vs interferon β-1a (IFNβ1a) in the individual Phase III OPERA I (NCT01247324) and OPERA II studies (NCT014112333), and in a prespecified analysis of the pooled populations.
Objective: To assess the effect of OCR vs IFNβ1a on NEDA status 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, proportions of patients with NEDA (absence of 12-week confirmed disability progression, protocol-defined relapse, new/enlarging T2 lesions or T1 Gd+ lesions) were compared using the Cochran-Mantel-Haenszel test based on the modified intent-to-treat population (exclusion of patients discontinuing treatment for reasons other than lack of efficacy or death and had NEDA prior to discontinuation) of the pooled OPERA studies (OCR, n=761; IFNβ1a, n=759); p values relate to NEDA for OCR vs IFNβ1a.
Results: Patient numbers and characteristics were comparable between treatments and within each subgroup stratum. The increase in the proportion of patients with NEDA with OCR (47.7%) vs IFNβ1a (27.1%) in the overall pooled population (p< 0.001) was maintained across all subgroups and strata; however, variations in the magnitude with OCR vs IFNβ1a were seen. Results by subgroup were as follows: age (< 40 years: OCR 44.3%, IFNβ1a 22.6%, p< 0.001; ≥40 years: OCR 52.8%, IFNβ1a 33.7%, p< 0.001), gender (male: OCR 44.0%, IFNβ1a 22.2%, p< 0.001; female: OCR 49.7%, IFNβ1a 29.6%,
p< 0.001), prior disease-modifying therapy use in the last 2 years (yes: OCR 42.8%, IFNβ1a 23.9%,
p< 0.001; no: OCR 49.5%, IFNβ1a 28.3%, p< 0.001), baseline Expanded Disability Status Scale (EDSS) score < 2.5/≥2.5 (< 2.5: OCR 50.5%, IFNβ1a 27.5%, p< 0.001; ≥2.5: OCR 46.0%, IFNβ1a 26.9%,
p< 0.001) baseline EDSS score < 4/≥4 (< 4: OCR 50.3%, IFNβ1a 26.4%, p< 0.001; ≥4: OCR 39.6%, IFNβ1a 29.4%, p=0.043), prior relapses in the last 12 months (≤1: OCR 49.2%, IFNβ1a 29.2%, p< 0.001; ≥2: OCR 44.2%, IFNβ1a 22.6%, p< 0.001) and T1 Gd+ lesions at baseline (none: OCR 59.6%, IFNβ1a 38.8%, p< 0.001; ≥1: OCR 30.1%, IFNβ1a 10.2%, p< 0.001).
Conclusions: The results of these subgroup analyses were consistent with those of the overall pooled population on maintaining NEDA status.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
B. Turner has received honoraria, travel grants and been a member of advisory boards for Biogen, Merck Serono, Novartis, Sanofi Genzyme and Roche.
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.
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: P688
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Ocrelizumab (OCR), a humanised, CD20+ B cell-selective monoclonal antibody, increased the proportion of patients with relapsing MS (RMS) with no evidence of disease activity (NEDA) vs interferon β-1a (IFNβ1a) in the individual Phase III OPERA I (NCT01247324) and OPERA II studies (NCT014112333), and in a prespecified analysis of the pooled populations.
Objective: To assess the effect of OCR vs IFNβ1a on NEDA status 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, proportions of patients with NEDA (absence of 12-week confirmed disability progression, protocol-defined relapse, new/enlarging T2 lesions or T1 Gd+ lesions) were compared using the Cochran-Mantel-Haenszel test based on the modified intent-to-treat population (exclusion of patients discontinuing treatment for reasons other than lack of efficacy or death and had NEDA prior to discontinuation) of the pooled OPERA studies (OCR, n=761; IFNβ1a, n=759); p values relate to NEDA for OCR vs IFNβ1a.
Results: Patient numbers and characteristics were comparable between treatments and within each subgroup stratum. The increase in the proportion of patients with NEDA with OCR (47.7%) vs IFNβ1a (27.1%) in the overall pooled population (p< 0.001) was maintained across all subgroups and strata; however, variations in the magnitude with OCR vs IFNβ1a were seen. Results by subgroup were as follows: age (< 40 years: OCR 44.3%, IFNβ1a 22.6%, p< 0.001; ≥40 years: OCR 52.8%, IFNβ1a 33.7%, p< 0.001), gender (male: OCR 44.0%, IFNβ1a 22.2%, p< 0.001; female: OCR 49.7%, IFNβ1a 29.6%,
p< 0.001), prior disease-modifying therapy use in the last 2 years (yes: OCR 42.8%, IFNβ1a 23.9%,
p< 0.001; no: OCR 49.5%, IFNβ1a 28.3%, p< 0.001), baseline Expanded Disability Status Scale (EDSS) score < 2.5/≥2.5 (< 2.5: OCR 50.5%, IFNβ1a 27.5%, p< 0.001; ≥2.5: OCR 46.0%, IFNβ1a 26.9%,
p< 0.001) baseline EDSS score < 4/≥4 (< 4: OCR 50.3%, IFNβ1a 26.4%, p< 0.001; ≥4: OCR 39.6%, IFNβ1a 29.4%, p=0.043), prior relapses in the last 12 months (≤1: OCR 49.2%, IFNβ1a 29.2%, p< 0.001; ≥2: OCR 44.2%, IFNβ1a 22.6%, p< 0.001) and T1 Gd+ lesions at baseline (none: OCR 59.6%, IFNβ1a 38.8%, p< 0.001; ≥1: OCR 30.1%, IFNβ1a 10.2%, p< 0.001).
Conclusions: The results of these subgroup analyses were consistent with those of the overall pooled population on maintaining NEDA status.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
B. Turner has received honoraria, travel grants and been a member of advisory boards for Biogen, Merck Serono, Novartis, Sanofi Genzyme and Roche.
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.
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.