Assessment of ixekizumab,an interleukin-17A monoclonal antibody,for potential effects on reproduction and development,including immune system function,in cynomolgus monkeys |
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| Affiliation: | 1. Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, United States;2. Charles River Laboratories, 6995 Longley Lane, Reno, NV 89511, United States;1. Division of Arthritis & Rheumatic Diseases, Oregon Health & Science University, Portland, OR, USA;2. Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands;3. University of California, San Francisco, San Francisco, CA, USA;4. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea;5. University of Alberta, Edmonton, AB, Canada;6. Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet Glostrup, Glostrup, Denmark;7. Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Berlin, Germany;8. National Institute for Health Research, Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds, UK;9. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK;10. Department of Medicine, Laval University, Québec City, QC, Canada;11. Department of Orthopaedic Biomaterial Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan;12. Syneos Health, Morrisville, NC, USA;13. Eli Lilly and Company, Indianapolis, IN, USA;1. Rheumatology Deparment, Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, IMSS, Seris y Zaachila s/n, Col. La Raza, Del. Azcapotzalco, 02990, Mexico City, Mexico;2. Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Cd. Universitaria, 04510, Coyoacan, Mexico City, Mexico;3. Rheumatology Deparment, Hospital Civil de Guadajara Fray Antonio Alcalde, Coronel Calderon 777, El Retiro, 44280, Guadalajara, Jal., Mexico;4. Rheumatology Deparment, Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Seris y Zaachila s/n, Col. La Raza, Del. Azcapotzalco, 02990, Mexico City, Mexico;5. Rheumatology Deparment, Hospital Civil de Guadajara Fray Antonio Alcalde, Coronel Calderon 777, El Retiro, 44280, Guadalajara, Jal., Mexico;6. Direction of Education and Investigation, Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, IMSS, Seris y Zaachila s/n, Col. La Raza, Del. Azcapotzalco, 02990, Mexico City, Mexico;1. Danish Ramazzini Center, Department of Occupational Medicine, Aarhus University Hospital, Nørrebrogade 44, build.2c, 8000 Aarhus C, Denmark;2. Primary Health Care Clinic, Postbox 570, DK-3900 Nuuk, Greenland;3. Departement of Social Medicine and Organization of Public Health, Kharkiv National Medical University, 61022 Kharkiv, Ukraine;4. Division of Occupational and Environmental Medicine, Lund University, S-221 85 Lund, Sweden;5. Department of Occupational and Environmental Medicine, Copenhagen University Hospital, Bispebjerg Bakke 23, 2400 Copenhagen NV, Denmark;6. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Alle 43-45, 8200 Aarhus N, Denmark |
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| Abstract: | The reproductive and developmental toxicity of ixekizumab, a selective inhibitor of interleukin-17A (IL-17A), was assessed in the following studies in cynomolgus monkeys: fertility (3-month dosing), embryo-fetal development (EFD; dosing from gestation day (GD) 20 through 139), and pre-postnatal development (PPND; dosing from GD 20 through parturition). Because IL-17A has functional roles in innate and humoral immunity, immune system modulation was evaluated in the EFD and PPND studies; immunological evaluations in infants comprised peripheral blood immunophenotyping, Natural Killer cell cytolytic activity, and T-cell-dependent antibody (IgG and IgM) primary and secondary responses to antigen challenge. Ixekizumab exposure was sustained during the dosing periods in most adult monkeys. Fetal exposure at Cesarean section (GD 140–142; EFD study) was 18–25% of maternal exposure and ixekizumab was present in infants for up to 29 weeks postpartum. There were no adverse effects attributed to ixekizumab in any study. Importantly, immune system development and maturation were unaffected. |
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| Keywords: | Cynomolgus monkey Embryo-fetal Fertility Ixekizumab Pre-postnatal Toxicity |
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