Contributions
Abstract: EP1671
Type: ePoster
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) and primary progressive (PPMS) multiple sclerosis. Infusion-related reactions (IRRs) in OCR Phase III studies, including the separate double-blind, double-dummy OPERA I and II studies (RMS; OCR N=825; comparator: interferon β-1a 44 µg three times weekly; NCT01247324 and NCT01412333) and ORATORIO (PPMS; comparator: placebo; NCT01194570) have been reported.
Objective: To define the pattern and characteristics of OCR IRRs in the prespecified pooled analysis of OPERA I and OPERA II, and ORATORIO.
Methods: OCR was given as 600 mg infusions every 24 weeks in OPERA I and OPERA II (96-week controlled period; 1st infusion: 2 × 300 mg infusions split by 14 days) and ORATORIO (at least 120 weeks' controlled treatment until a set number of disease progression events was seen; 2 × 300 mg infusions split by 14 days). Pretreatment per protocol was methylprednisolone (MP) 100 mg intravenous (or equivalent); antihistamines and analgesics/antipyretics were recommended. Populations of interest were those with an IRR (≥1 or >1), a Day 1 IRR (with/without ≥1 later IRRs) and those without Day 1 IRRs with a later IRR. Subgroups were also analysed by pretreatment.
Results: Overall, 283 of 825 (34.3%) of OCR recipients in the pooled OPERA analysis had ≥1 IRR; of these, 123 patients (14.9%) had >1 IRR. 227 patients (27.5%) had an IRR on Day 1, of which 106 patients (12.8%) had a further IRR; 56 patients (6.8%) had an IRR after not having an IRR on Day 1. Most IRRs were mild to moderate in severity and generally manageable including by infusion adjustments; one life-threatening IRR (Day 1; bronchospasm; MP alone pretreatment) and no fatal IRRs occurred. 11 patients (1.3%) discontinued due to IRRs. Fewer IRRs were seen in patients pretreated with MP + antihistamines (N=120; ≥1 IRR, 29.2% [n=35]; >1 IRR, 9.2% [n=11]; Day 1 IRR, 19.2% [n=23]) vs other pretreatment groups (≥1 IRR, 31.2-52.6%; >1 IRR, 14.5-21.6%; Day 1 IRR, 24.9-49.5%). ORATORIO study results will be presented.
Conclusions: IRRs were a common adverse event experienced by 34.3% of patients (≥1 IRR) and most frequently occurred at the first vs later infusions. IRRs were generally mild to moderate in severity, manageable (including infusion adjustments) and less frequent with a combination of premedication with MP + antihistamines before each infusion vs other pretreatment groups.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
J. de Seze has received consultancy fees and served as an expert for advisory boards for Alexion, Allergan, Almirall, Bayer, Biogen, Chugai, CSL Behring, F. Hoffmann-La Roche Ltd, Genzyme, LFB, Merck, Novartis, Sanofi and Teva.
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.
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; royalties from Neurostatus AG; research grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, the Novartis Research Foundation and the Roche Research Foundation.
X. Montalban has received speaker 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.
C. Pozzilli has served on scientific advisory boards for Actelion, Biogen, Genzyme, F. Hoffmann-La Roche Ltd, Merck Serono, Novartis, Sanofi and Teva, and has received consulting and/or speaking fees, research support and travel grants from Allergan, Almirall, Biogen, Genzyme, F. Hoffmann-La Roche Ltd, Merck Serono, Novartis, Sanofi and Teva.
C. Chognot is an employee of F. Hoffmann-La Roche Ltd.
L. Julian is an employee and shareholder of Genentech, Inc.
H. Koendgen is an employee and shareholder of F. Hoffmann-La Roche Ltd
H. Zheng is an employee of Genentech, Inc.
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.
Abstract: EP1671
Type: ePoster
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) and primary progressive (PPMS) multiple sclerosis. Infusion-related reactions (IRRs) in OCR Phase III studies, including the separate double-blind, double-dummy OPERA I and II studies (RMS; OCR N=825; comparator: interferon β-1a 44 µg three times weekly; NCT01247324 and NCT01412333) and ORATORIO (PPMS; comparator: placebo; NCT01194570) have been reported.
Objective: To define the pattern and characteristics of OCR IRRs in the prespecified pooled analysis of OPERA I and OPERA II, and ORATORIO.
Methods: OCR was given as 600 mg infusions every 24 weeks in OPERA I and OPERA II (96-week controlled period; 1st infusion: 2 × 300 mg infusions split by 14 days) and ORATORIO (at least 120 weeks' controlled treatment until a set number of disease progression events was seen; 2 × 300 mg infusions split by 14 days). Pretreatment per protocol was methylprednisolone (MP) 100 mg intravenous (or equivalent); antihistamines and analgesics/antipyretics were recommended. Populations of interest were those with an IRR (≥1 or >1), a Day 1 IRR (with/without ≥1 later IRRs) and those without Day 1 IRRs with a later IRR. Subgroups were also analysed by pretreatment.
Results: Overall, 283 of 825 (34.3%) of OCR recipients in the pooled OPERA analysis had ≥1 IRR; of these, 123 patients (14.9%) had >1 IRR. 227 patients (27.5%) had an IRR on Day 1, of which 106 patients (12.8%) had a further IRR; 56 patients (6.8%) had an IRR after not having an IRR on Day 1. Most IRRs were mild to moderate in severity and generally manageable including by infusion adjustments; one life-threatening IRR (Day 1; bronchospasm; MP alone pretreatment) and no fatal IRRs occurred. 11 patients (1.3%) discontinued due to IRRs. Fewer IRRs were seen in patients pretreated with MP + antihistamines (N=120; ≥1 IRR, 29.2% [n=35]; >1 IRR, 9.2% [n=11]; Day 1 IRR, 19.2% [n=23]) vs other pretreatment groups (≥1 IRR, 31.2-52.6%; >1 IRR, 14.5-21.6%; Day 1 IRR, 24.9-49.5%). ORATORIO study results will be presented.
Conclusions: IRRs were a common adverse event experienced by 34.3% of patients (≥1 IRR) and most frequently occurred at the first vs later infusions. IRRs were generally mild to moderate in severity, manageable (including infusion adjustments) and less frequent with a combination of premedication with MP + antihistamines before each infusion vs other pretreatment groups.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
J. de Seze has received consultancy fees and served as an expert for advisory boards for Alexion, Allergan, Almirall, Bayer, Biogen, Chugai, CSL Behring, F. Hoffmann-La Roche Ltd, Genzyme, LFB, Merck, Novartis, Sanofi and Teva.
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.
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; royalties from Neurostatus AG; research grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, the Novartis Research Foundation and the Roche Research Foundation.
X. Montalban has received speaker 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.
C. Pozzilli has served on scientific advisory boards for Actelion, Biogen, Genzyme, F. Hoffmann-La Roche Ltd, Merck Serono, Novartis, Sanofi and Teva, and has received consulting and/or speaking fees, research support and travel grants from Allergan, Almirall, Biogen, Genzyme, F. Hoffmann-La Roche Ltd, Merck Serono, Novartis, Sanofi and Teva.
C. Chognot is an employee of F. Hoffmann-La Roche Ltd.
L. Julian is an employee and shareholder of Genentech, Inc.
H. Koendgen is an employee and shareholder of F. Hoffmann-La Roche Ltd
H. Zheng is an employee of Genentech, Inc.
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.