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

被引:114
|
作者
Hoeltzenbein, Maria [1 ]
Becka, Evelin [1 ]
Rajwanshi, Richa [2 ]
Skorpen, Carina Gotestam [3 ,4 ,5 ]
Berber, Erhan [2 ]
Schaefer, Christof [1 ]
Ostensen, Monika [3 ,4 ]
机构
[1] Charite, Inst Clin Teratol & Drug Risk Assessment Pregnanc, Augustenburger Pl 1, D-13353 Berlin, Germany
[2] Genentech Inc, San Francisco, CA 94080 USA
[3] Univ Trondheim Hosp, Dept Rheumatol, Natl Serv Pregnancy & Rheumat Dis, Trondheim, Norway
[4] Norwegian Univ Sci & Technol NTNU, Dept Neurosci, Trondheim, Norway
[5] Alesund Hosp, Dept Rheumatol, Alesund, Norway
关键词
Tocilizumab; Rheumatoid arthritis; Pregnancy; Maternal exposure; Malformation; Spontaneous abortion; LOWER BIRTH-WEIGHT; RHEUMATOID-ARTHRITIS; DISEASE-ACTIVITY; OUTCOMES; WOMEN; MISCARRIAGE; PREVALENCE; EXPOSURE; PROJECT;
D O I
10.1016/j.semarthrit.2016.05.004
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 birth's (60.6%), 39 spontaneous abortions (21.7%), 31 elective terminations of pregnancy (17.2%), and I 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. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:238 / 245
页数:8
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