Contributions
Abstract: P1248
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Increased risk of infection has been reported with multiple sclerosis (MS) disease-modifying treatments; assessment of infection is an important component of the ocrelizumab (OCR) safety profile. OCR was evaluated in patients with relapsing MS (RMS; two identical, Phase III, interferon beta-1a [IFNβ-1a]-controlled studies [OPERA I and II]) and primary progressive MS (PPMS; a Phase III, placebo [PBO] -controlled study [ORATORIO]).
Objective: To evaluate infections and serious infections in patients with RMS or PPMS treated with OCR.
Methods: In OPERA I and II, patients were randomised 1:1 to OCR 600mg via intravenous (IV) infusion every 24 weeks or IFNβ‐1a 44µg three-times weekly for 96 weeks. In ORATORIO, patients were randomised 2:1 to OCR 600mg as two 300mg IV infusions 14 days apart, or matched PBO every 24 weeks for ≥120 weeks. Infections were classified by the Medical Dictionary for Regulatory Activities system organ class and preferred term.
Results: In pooled analyses of OPERA, the proportion of patients reporting an infection was 58.4% and 52.4% in the OCR and IFNβ-1a groups, respectively; common infections (≥10% in either group) reported more frequently in the OCR group were upper respiratory tract infections (URTI) and nasopharyngitis. Most infections were mild to moderate and recovered on treatment. Two OCR-treated patients (< 1%; both non-serious) withdrew due to infections. The proportion with any serious infection was 1.3% in the OCR group and 2.9% in the IFNβ-1a group. In ORATORIO, the proportion of patients reporting an infection was 69.8% and 67.8% in the OCR and PBO groups, respectively; common infections (≥10% in either group) reported more frequently in the OCR group were URTI and influenza. Most infections were mild to moderate, and the rate of withdrawal due to infections was low (OCR, 0.8%; PBO, 1.3%).The proportion of patients with serious infections was 6.2% and 5.9% in the OCR and PBO groups, respectively. No opportunistic infections were reported in any study over the controlled treatment periods. There were no deaths related to infection in OPERA and two deaths (< 1%) in ORATORIO in the OCR group (pneumonia aspiration and pneumonia; unrelated to OCR per investigator and related per sponsor).
Conclusion: The proportion of serious infections was numerically lower in patients treated with OCR compared with IFNβ-1a in patients with RMS and similar compared with PBO in patients with PPMS.
Sponsored by F. Hoffmann-La Roche Ltd.
Disclosure: Douglas Arnold reports equity interest in NeuroRx Research, which performed the MRI analysis for the trial, and consultation fees from Acorda Therapeutics, Biogen, Genzyme, F. Hoffmann-La Roche Ltd., Innate Immunotherapeutics, MedImmune, Mitsubishi Pharma, Novartis, Receptos, Sanofi, and Teva.
Amit Bar-Or has served on scientific advisory boards for F. Hoffmann-La Roche Ltd., Genentech, Biogen Idec, GlaxoSmithKline, Merck/EMD Serono, Medimmune, Mitsubishi Pharma, Ono Pharma, Receptos, Sanofi-Genzyme, and Guthy-Jackson/GGF; he has also received research support from Novartis and Sanofi-Genzyme.
Giancarlo Comi has received compensation for consulting services from Roche, Novartis, Teva, Sanofi, Genzyme, Merck, Excemed, Almirall, Chugai, Receptos, Forward Pharma, and received compensation for speaking activities from Roche, Novartis, Teva, Sanofi, Genzyme, Merck, Excemed, Almirall, Receptos.
Jérôme de Seze has received consultancy fees and served as an expert for advisory boards for Alexion, Allergan, Almiral, Bayer, Biogen, Chugai, CSL Behring, F. Hoffmann-La Roche Ltd., Genzyme, LFB, Merck, Novartis, and Teva.
Gavin 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.
Hans-Peter Hartung has received honoraria for consulting, serving on steering committees and speaking at scientific symposia with approval by the Rector of Heinrich-Heine-University from Bayer, Biogen, GeNeuro, Genzyme, Merck Serono, MedImmune, Novartis, Octapharma, Opexa, F. Hoffmann-La Roche Ltd., Teva, and Sanofi.
Stephen L Hauser serves on the scientific advisory boards for Annexon, Symbiotix, Bionure; he has also received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd. for CD20-related meetings and presentations.
Bernhard Hemmer has served on scientific advisory boards for Roche, Novartis, Bayer Schering, and Genentech; has received speaker honoraria from Biogen Idec and Roche; and has received research support from Chugai Pharmaceuticals. He holds part of a patent for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and genetic determinants of neutralizing antibodies to interferon-beta.
Ludwig Kappos"s institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos" activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer Health Care 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 Xenport; royalties from Neurostatus AG; research grants from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, and the Novartis Research Foundation and Roche Research Foundation.
Fred Lublin reports funding of research from Biogen Idec, Novartis Pharmaceuticals Corp,
Teva Neuroscience, Inc., Genzyme, Sanofi, Celgene, Transparency Life Sciences, NIH, NMSS; consulting agreements/advisory boards/DSMB for Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Inc., Novartis, Teva Neuroscience, Actelion, Sanofi, Acorda, Questcor/Malinckrodt, 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 Diseases; and has current financial interests/stock ownership in Cognition Pharmaceuticals, Inc.
Xavier 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.
Kottil Rammohan has received honoraria for participating in advisory boards and consulting for Acorda, Biogen, EMD Serono, Genentech, Inc./F. Hoffmann-La Roche Ltd., Genzyme and Teva; he has also received grants from Accera.
Krzysztof Selmaj has received honoraria for advisory boards from Biogen, Novartis, Teva, F. Hoffmann-La Roche Ltd., Merck, Synthon, Receptos, and Genzyme.
Anthony Traboulsee has received honoraria for advisory boards from Genzyme F. Hoffmann-La Roche Ltd. He is a steering committee member for F. Hoffmann-La Roche Ltd.
Jerry Wolinsky in the last 3 years has received compensation for service on steering committees or data monitoring boards for F. Hoffmann-La Roche Ltd., Medday Pharmaceuticals, Novartis, Sanofi Genzyme and Teva Pharmaceuticals; consultant fees from AbbVie, Actelion, Alkermes, EMD Serono, Forward Pharma, Genentech, Inc., F. Hoffmann-La Roche Ltd., Novartis, Sanofi Genzyme, Takeda, Teva, and XenoPort; research support from, Sanofi Genzyme, the NIH and the NMSS through the University of Texas Health Science Center at Houston (UTHSCH) and royalties for monoclonal antibodies out-licensed to Chemicon International through UTHSCH.
Carrie Li is an employee of F. Hoffmann-La Roche Ltd.
Nicole Mairon is an employee and/or shareholder of F. Hoffmann-La Roche Ltd.
Donna Masterman is an employee and/or shareholder of Genentech, Inc.
Julie Napieralski is an employee of F. Hoffmann-La Roche Ltd.
Abstract: P1248
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Increased risk of infection has been reported with multiple sclerosis (MS) disease-modifying treatments; assessment of infection is an important component of the ocrelizumab (OCR) safety profile. OCR was evaluated in patients with relapsing MS (RMS; two identical, Phase III, interferon beta-1a [IFNβ-1a]-controlled studies [OPERA I and II]) and primary progressive MS (PPMS; a Phase III, placebo [PBO] -controlled study [ORATORIO]).
Objective: To evaluate infections and serious infections in patients with RMS or PPMS treated with OCR.
Methods: In OPERA I and II, patients were randomised 1:1 to OCR 600mg via intravenous (IV) infusion every 24 weeks or IFNβ‐1a 44µg three-times weekly for 96 weeks. In ORATORIO, patients were randomised 2:1 to OCR 600mg as two 300mg IV infusions 14 days apart, or matched PBO every 24 weeks for ≥120 weeks. Infections were classified by the Medical Dictionary for Regulatory Activities system organ class and preferred term.
Results: In pooled analyses of OPERA, the proportion of patients reporting an infection was 58.4% and 52.4% in the OCR and IFNβ-1a groups, respectively; common infections (≥10% in either group) reported more frequently in the OCR group were upper respiratory tract infections (URTI) and nasopharyngitis. Most infections were mild to moderate and recovered on treatment. Two OCR-treated patients (< 1%; both non-serious) withdrew due to infections. The proportion with any serious infection was 1.3% in the OCR group and 2.9% in the IFNβ-1a group. In ORATORIO, the proportion of patients reporting an infection was 69.8% and 67.8% in the OCR and PBO groups, respectively; common infections (≥10% in either group) reported more frequently in the OCR group were URTI and influenza. Most infections were mild to moderate, and the rate of withdrawal due to infections was low (OCR, 0.8%; PBO, 1.3%).The proportion of patients with serious infections was 6.2% and 5.9% in the OCR and PBO groups, respectively. No opportunistic infections were reported in any study over the controlled treatment periods. There were no deaths related to infection in OPERA and two deaths (< 1%) in ORATORIO in the OCR group (pneumonia aspiration and pneumonia; unrelated to OCR per investigator and related per sponsor).
Conclusion: The proportion of serious infections was numerically lower in patients treated with OCR compared with IFNβ-1a in patients with RMS and similar compared with PBO in patients with PPMS.
Sponsored by F. Hoffmann-La Roche Ltd.
Disclosure: Douglas Arnold reports equity interest in NeuroRx Research, which performed the MRI analysis for the trial, and consultation fees from Acorda Therapeutics, Biogen, Genzyme, F. Hoffmann-La Roche Ltd., Innate Immunotherapeutics, MedImmune, Mitsubishi Pharma, Novartis, Receptos, Sanofi, and Teva.
Amit Bar-Or has served on scientific advisory boards for F. Hoffmann-La Roche Ltd., Genentech, Biogen Idec, GlaxoSmithKline, Merck/EMD Serono, Medimmune, Mitsubishi Pharma, Ono Pharma, Receptos, Sanofi-Genzyme, and Guthy-Jackson/GGF; he has also received research support from Novartis and Sanofi-Genzyme.
Giancarlo Comi has received compensation for consulting services from Roche, Novartis, Teva, Sanofi, Genzyme, Merck, Excemed, Almirall, Chugai, Receptos, Forward Pharma, and received compensation for speaking activities from Roche, Novartis, Teva, Sanofi, Genzyme, Merck, Excemed, Almirall, Receptos.
Jérôme de Seze has received consultancy fees and served as an expert for advisory boards for Alexion, Allergan, Almiral, Bayer, Biogen, Chugai, CSL Behring, F. Hoffmann-La Roche Ltd., Genzyme, LFB, Merck, Novartis, and Teva.
Gavin 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.
Hans-Peter Hartung has received honoraria for consulting, serving on steering committees and speaking at scientific symposia with approval by the Rector of Heinrich-Heine-University from Bayer, Biogen, GeNeuro, Genzyme, Merck Serono, MedImmune, Novartis, Octapharma, Opexa, F. Hoffmann-La Roche Ltd., Teva, and Sanofi.
Stephen L Hauser serves on the scientific advisory boards for Annexon, Symbiotix, Bionure; he has also received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd. for CD20-related meetings and presentations.
Bernhard Hemmer has served on scientific advisory boards for Roche, Novartis, Bayer Schering, and Genentech; has received speaker honoraria from Biogen Idec and Roche; and has received research support from Chugai Pharmaceuticals. He holds part of a patent for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and genetic determinants of neutralizing antibodies to interferon-beta.
Ludwig Kappos"s institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos" activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer Health Care 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 Xenport; royalties from Neurostatus AG; research grants from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, and the Novartis Research Foundation and Roche Research Foundation.
Fred Lublin reports funding of research from Biogen Idec, Novartis Pharmaceuticals Corp,
Teva Neuroscience, Inc., Genzyme, Sanofi, Celgene, Transparency Life Sciences, NIH, NMSS; consulting agreements/advisory boards/DSMB for Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono, Inc., Novartis, Teva Neuroscience, Actelion, Sanofi, Acorda, Questcor/Malinckrodt, 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 Diseases; and has current financial interests/stock ownership in Cognition Pharmaceuticals, Inc.
Xavier 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.
Kottil Rammohan has received honoraria for participating in advisory boards and consulting for Acorda, Biogen, EMD Serono, Genentech, Inc./F. Hoffmann-La Roche Ltd., Genzyme and Teva; he has also received grants from Accera.
Krzysztof Selmaj has received honoraria for advisory boards from Biogen, Novartis, Teva, F. Hoffmann-La Roche Ltd., Merck, Synthon, Receptos, and Genzyme.
Anthony Traboulsee has received honoraria for advisory boards from Genzyme F. Hoffmann-La Roche Ltd. He is a steering committee member for F. Hoffmann-La Roche Ltd.
Jerry Wolinsky in the last 3 years has received compensation for service on steering committees or data monitoring boards for F. Hoffmann-La Roche Ltd., Medday Pharmaceuticals, Novartis, Sanofi Genzyme and Teva Pharmaceuticals; consultant fees from AbbVie, Actelion, Alkermes, EMD Serono, Forward Pharma, Genentech, Inc., F. Hoffmann-La Roche Ltd., Novartis, Sanofi Genzyme, Takeda, Teva, and XenoPort; research support from, Sanofi Genzyme, the NIH and the NMSS through the University of Texas Health Science Center at Houston (UTHSCH) and royalties for monoclonal antibodies out-licensed to Chemicon International through UTHSCH.
Carrie Li is an employee of F. Hoffmann-La Roche Ltd.
Nicole Mairon is an employee and/or shareholder of F. Hoffmann-La Roche Ltd.
Donna Masterman is an employee and/or shareholder of Genentech, Inc.
Julie Napieralski is an employee of F. Hoffmann-La Roche Ltd.