title: Tocilizumab use in pregnancy: Analysis of a global safety database including data from clinical trials and post-marketing data.
abstract: Analyze the cumulative evidence for pregnancy outcomes after maternal exposure to tocilizumab, an anti-interleukin-6-receptor monoclonal antibody used for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. At present, published experience on tocilizumab use during pregnancy is very limited.
  
  
  
  We have analyzed all pregnancy-related reports documented in the Roche Global Safety Database until December 31, 2014 (n = 501).
  
  
  
  After exclusion of ongoing pregnancies, duplicates, and cases retrieved from the literature, 399 women were found to have been exposed to tocilizumab shortly before or during pregnancy, with pregnancy outcomes being reported in 288 pregnancies (72.2%). Of these 288 pregnancies, 180 were prospectively reported resulting in 109 live births (60.6%), 39 spontaneous abortions (21.7%), 31 elective terminations of pregnancy (17.2%), and 1 stillbirth. The rate of malformations was 4.5%. Co-medications included methotrexate in 21.1% of the prospectively ascertained cases. Compared to the general population, an increased rate of preterm birth (31.2%) was observed. Retrospectively reported pregnancies (n = 108) resulted in 55 live births (50.9%), 31 spontaneous abortions (28.7%), and 22 elective terminations (20.4%). Three infants/fetuses with congenital anomalies were reported in this group. No increased risks for adverse pregnancy outcomes were observed after paternal exposure in 13 pregnancies with known outcome.
  
  
  
  No indication for a substantially increased malformation risk was observed. Considering the limitations of global safety databases, the data do not yet prove safety, but provide information for physicians and patients to make informed decisions. This is particularly important after inadvertent exposure to tocilizumab, shortly before or during early pregnancy.
authors.affiliation: Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. Electronic address: maria.hoeltzenbein@charite.de.
authors.forename: Maria
authors.initials: M
authors.lastname: Hoeltzenbein
authors.affiliation: Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
authors.forename: Evelin
authors.initials: E
authors.lastname: Beck
authors.affiliation: Genentech, Inc., A Member of the Roche Group, South San Francisco, California, United States.
authors.forename: Richa
authors.initials: R
authors.lastname: Rajwanshi
authors.affiliation: National Service for Pregnancy and Rheumatic Diseases, Department of Rheumatology, Trondheim University Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Rheumatology, Ålesund Hospital, Ålesund, Norway.
authors.forename: Carina
authors.initials: C
authors.lastname: Gøtestam Skorpen
authors.affiliation: Genentech, Inc., A Member of the Roche Group, South San Francisco, California, United States.
authors.forename: Erhan
authors.initials: E
authors.lastname: Berber
authors.affiliation: Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Schaefer
authors.affiliation: National Service for Pregnancy and Rheumatic Diseases, Department of Rheumatology, Trondheim University Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Monika
authors.initials: M
authors.lastname: Østensen
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D018811:Maternal Exposure / Q000009:adverse effects; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011247:Pregnancy; D011256:Pregnancy Outcome; D011358:Product Surveillance, Postmarketing; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab; D008727:Methotrexate
keywords: Malformation; Maternal exposure; Pregnancy; Rheumatoid arthritis; Spontaneous abortion; Tocilizumab