Contributions
Abstract: P710
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Ocrelizumab, a humanised monoclonal antibody that selectively targets CD20+ B cells, is approved by the Food and Drug Administration for the treatment of relapsing and primary progressive forms of multiple sclerosis (MS), and has also been studied in clinical trials for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
Objective: To provide an update of pregnancy outcomes in women treated with ocrelizumab during clinical trials.
Methods: This analysis includes pregnancies in women with MS, RA and SLE in ocrelizumab clinical trials (dose range 20 to 2000 mg) up to 31 January 2017. Across trials, women of childbearing potential were required to use two methods of contraception and continue contraception for 48 weeks after the last ocrelizumab infusion or until B cells repleted, whichever was longer. Urine pregnancy tests were performed at all infusion visits; if positive, dosing was stopped and the result confirmed with a serum pregnancy test. An embryo/foetus was considered exposed to ocrelizumab in utero if the last infusion occurred within 3 months of conception or during pregnancy or if the date was unknown. All pregnancies occurring during clinical trials were followed to determine outcome.
Results: As previously reported, between 2008 and September 14, 2015, 46 women randomised to ocrelizumab in clinical trials (15 MS, 10 SLE, 21 RA) reported 48 pregnancies (15 MS, 11 SLE, 22 RA). This cumulative update provides approximately 16 months' additional data on pregnancies in clinical trials up to 31 January 2017, and will review 58 pregnancies reported in 56 women (25 MS and 31 non-MS). Among the 25 pregnancies in patients with MS, 13 were considered to have foetal ocrelizumab exposure. Eleven pregnancies had no foetal ocrelizumab exposure and one pregnancy is not assessable for foetal ocrelizumab exposure.
Conclusions: As a large proportion of patients with MS are women of reproductive age, pregnancy outcomes in patients exposed to ocrelizumab are important to understand. B-cell levels in neonates following maternal exposure to ocrelizumab have not been studied in clinical trials and the effect of ocrelizumab on the immune system of the newborn is unknown. Transient peripheral B-cell depletion and lymphocytopenia have been reported in some infants born to mothers exposed to other anti-CD20+ antibodies during pregnancy.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
S. Vukusic reports receiving consulting and lecture fees, travel grants and research support from Bayer-Schering, Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi Aventis and Teva Pharma.
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.
S. Wray has received honoraria and/or research funding from Actelion, Alkermes, Biogen, Cellgene, EMD Serono, Genentech/Roche, Genzyme/Sanofi, Novartis, TG Therapeutics.
S. Bader-Weder is an employee of F. Hoffmann-La Roche Ltd.
R. Buffels is an employee of F. Hoffmann-La Roche Ltd.
D. Masterman is an employee and/or shareholder of Genentech, Inc.
J. Napieralski is an employee 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: P710
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Ocrelizumab, a humanised monoclonal antibody that selectively targets CD20+ B cells, is approved by the Food and Drug Administration for the treatment of relapsing and primary progressive forms of multiple sclerosis (MS), and has also been studied in clinical trials for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
Objective: To provide an update of pregnancy outcomes in women treated with ocrelizumab during clinical trials.
Methods: This analysis includes pregnancies in women with MS, RA and SLE in ocrelizumab clinical trials (dose range 20 to 2000 mg) up to 31 January 2017. Across trials, women of childbearing potential were required to use two methods of contraception and continue contraception for 48 weeks after the last ocrelizumab infusion or until B cells repleted, whichever was longer. Urine pregnancy tests were performed at all infusion visits; if positive, dosing was stopped and the result confirmed with a serum pregnancy test. An embryo/foetus was considered exposed to ocrelizumab in utero if the last infusion occurred within 3 months of conception or during pregnancy or if the date was unknown. All pregnancies occurring during clinical trials were followed to determine outcome.
Results: As previously reported, between 2008 and September 14, 2015, 46 women randomised to ocrelizumab in clinical trials (15 MS, 10 SLE, 21 RA) reported 48 pregnancies (15 MS, 11 SLE, 22 RA). This cumulative update provides approximately 16 months' additional data on pregnancies in clinical trials up to 31 January 2017, and will review 58 pregnancies reported in 56 women (25 MS and 31 non-MS). Among the 25 pregnancies in patients with MS, 13 were considered to have foetal ocrelizumab exposure. Eleven pregnancies had no foetal ocrelizumab exposure and one pregnancy is not assessable for foetal ocrelizumab exposure.
Conclusions: As a large proportion of patients with MS are women of reproductive age, pregnancy outcomes in patients exposed to ocrelizumab are important to understand. B-cell levels in neonates following maternal exposure to ocrelizumab have not been studied in clinical trials and the effect of ocrelizumab on the immune system of the newborn is unknown. Transient peripheral B-cell depletion and lymphocytopenia have been reported in some infants born to mothers exposed to other anti-CD20+ antibodies during pregnancy.
Disclosure: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
S. Vukusic reports receiving consulting and lecture fees, travel grants and research support from Bayer-Schering, Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi Aventis and Teva Pharma.
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.
S. Wray has received honoraria and/or research funding from Actelion, Alkermes, Biogen, Cellgene, EMD Serono, Genentech/Roche, Genzyme/Sanofi, Novartis, TG Therapeutics.
S. Bader-Weder is an employee of F. Hoffmann-La Roche Ltd.
R. Buffels is an employee of F. Hoffmann-La Roche Ltd.
D. Masterman is an employee and/or shareholder of Genentech, Inc.
J. Napieralski is an employee 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.