Tocilizumab use in pregnancy: analysis of a global safety database including data from clinical trials and post-marketing data

• Published in: Seminars in arthritis and rheumatism 2016-10, Vol.46 (2), p.238-245
• Main Authors: Hoeltzenbein, Maria, Beck, Evelin, Rajwanshi, Richa, Gøtestam Skorpen, Carina, Berber, Erhan, Schaefer, Christof, Østensen, Monika
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced - etiology; Adolescent; Adult; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Databases, Factual; Drug Therapy, Combination; Female; Humans; Malformation; Maternal exposure; Maternal Exposure - adverse effects; Methotrexate - adverse effects; Methotrexate - therapeutic use; Middle Aged; Pregnancy; Pregnancy Outcome; Product Surveillance, Postmarketing; Rheumatoid arthritis; Rheumatology; Risk Assessment; Spontaneous abortion; Tocilizumab; Young Adult
• ISSN: 0049-0172; 1532-866X
• DOI: 10.1016/j.semarthrit.2016.05.004

Abstract Objectives 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. Methods We have analyzed all pregnancy-related reports documented in the Roche Global Safety Database until December 31, 2014 (n=501). Results 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. Conclusions 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.