Belimumab use during pregnancy: a summary of birth defects and pregnancy loss from belimumab clinical trials, a pregnancy registry and postmarketing reports.

Objective: Describe available data on birth defects and pregnancy loss in women with systemic lupus erythematosus (SLE) exposed to belimumab.
Methods: Data collected from belimumab clinical trials, the Belimumab Pregnancy Registry (BPR), and postmarketing/spontaneous reports up to 8 March 2020 were described. Belimumab exposure timing, concomitant medications and potential confounding factors were summarised descriptively.
Results: Among 319 pregnancies with known outcomes (excluding elective terminations), 223 ended in live births from which birth defects were identified in 4/72 (5.6%) in belimumab-exposed pregnancies and 0/9 placebo-exposed pregnancies across 18 clinical trials, 10/46 (21.7%) belimumab-exposed pregnancies in the BPR prospective cohort (enrolled prior to pregnancy outcome) and 0/4 belimumab-exposed pregnancies in the BPR retrospective cohort (enrolled after pregnancy outcome), and 1/92 (1.1%) in belimumab-exposed pregnancies from postmarketing/spontaneous reports. There was no consistent pattern of birth defects across datasets. Out of pregnancies with known outcomes (excluding elective terminations), pregnancy loss occurred in 31.8% (35/110) of belimumab-exposed women and 43.8% (7/16) of placebo-exposed women in clinical trials; 4.2% (2/48) of women in the BPR prospective cohort and 50% (4/8) in the BPR retrospective cohort; and 31.4% (43/137) of belimumab-exposed women from postmarketing/spontaneous reports. All belimumab-exposed women in clinical trials and the BPR received concomitant medications and had confounding factors and/or missing data.
Conclusions: Observations reported here add to limited data published on pregnancy outcomes following belimumab exposure. Low numbers of exposed pregnancies, presence of confounding factors/other biases, and incomplete information preclude informed recommendations regarding risk of birth defects and pregnancy loss with belimumab use.
Competing Interests: Competing interests: KG, MKh, RAL, AL, RM, MBC, KW, JHNH, HQ, PJ and DAR are employees of GSK and hold shares in the company. KG is a previous employee of Novartis and holds shares in the company. At the time of the study, MKu, PM and JMP were employees of GSK and hold shares in the company. MP received grant support from GSK and is a member of the BPR Scientific Advisory Committee. HL received royalties/licences from UpToDate Inc (Wolters Kluwer Health), has received consulting fees from AMAG Pharmaceuticals and is a member of the BPR Scientific Advisory Committee. KS is employed by the University of North Carolina at Chapel Hill to assist GSK with research. HT is a member of the BPR Scientific Advisory Committee and a GSK retiree. MEBC received grants from GSK and UCB, and acted as a consultant to GSK and UCB. RAL is the guarantor.
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