Table 5.

Published registries.

Reference	Objective	Methods	Results	Foetal outcome	Conclusions
Petri M, et al, 2023 23	To describe available data on birth defects and pregnancy loss in women with SLE exposed to belimumab	Data on birth defects and pregnancy loss (miscarriage or stillbirth) with belimumab exposures prior to or during pregnancy were collected from 18 belimumab clinical trials, the belimumab pregnancy registry (BPR, GSK study BEL114256; NCT01532310) and postmarketing/spontaneous reports from the argus database (which included searches of the US FDA adverse event reporting System and EV databases) up to 8 March 2020	A total of 586 pregnancy reports were identified 319 pregnancies with known outcomes excluding elective terminations were analysed: 126 were identified in clinical trials (n = 110 belimumab, n = 16 placebo); 56 (n = 48 prospective, n = 8 retrospective) were identified in the BPR; and 137 were postmarketing/spontaneous reports 223 ended in live births	Birth defects were identified − 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) − 0/4 belimumab-exposed pregnancies in the BPR retrospective cohort (enrolled after pregnancy outcome) − 1/92 (1.1%) in belimumab-exposed pregnancies from postmarketing/spontaneous reports There was no consistent pattern of birth defects across datasets 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 − 50% (4/8) in the BPR retrospective cohort −31.4% (43/137) of belimumab-exposed women from postmarketing/spontaneous reports	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
Ghalandari N, et al, 2022 24	To evaluate the number and nature of reported CMs after intrauterine exposure to non-TNF inhibitor biologics compared to CZP.	A search was performed in the EV database among pregnancy-related ADR reports (all reports until 11 March 2021)	There were 93 reports of pregnancies with belimumab	Of the 93 reports of pregnancies with belimumab, 17 (18.27%) involved CMs. Compared to CZP, belimumab had a statistically significantly higher crude and adjusted OR of CMs. The most reported CM were cardiac or neurological disorders, but no specific patterns were observed. It must be considered that previous reports have shown a risk ratio for CMs in neonates born to SLE patients comparable to the result of this study	No special safety signal was identified regarding the occurrence of CMs after exposure to belimumab
Ghalandari N, et al. 2023 25	To compare the reported foetal outcomes in SLE patients who stopped scheduled belimumab within the first trimester (group A) and those who continued (group B)	All belimumab-exposed pregnancy-related reports were extracted from the EV database until March 11th, 2021	87 pregnancies with 90 foetal outcomes were included (including three twin pregnancies) -Group A, n = 68 -Group B, n = 20	-Exposure to concomitant medications aimed for management of SLE (corticosteroids, NSAID, azathioprine, MTX and mycophenolate mofetil, were higher in group A -Reporting rates of preterm birth and low birth weight were higher – though not statistically different – in group A. -No statistical difference in foetal death was observed between groups	The positive results are supportive for the continuation of belimumab during pregnancy
Dernoncourt A, et al, 2023 26	To detect pharmacovigilance signals for foetal and neonatal adverse drug reactions (ADRs) to biologics taken by pregnant women with autoimmune diseases	A disproportionality analysis of VigiBase pharmacovigilance was performed The frequency of all identified ADRs for biologics of interest was compared with that of all other reports for all other drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval]	The total number of individual case safety reports with belimumab was 112	After the exclusion of reports with steroids, the ROR was significant for neonatal infections with belimumab (28.49 [5.75–141.25]) The RORs for musculoskeletal malformations was not elevated with belimumab	The reporting odds ratios were not elevated for musculoskeletal malformations but were significant for neonatal infections

CMs, congenital malformations; CZP, certolizumab pegol; EV database, EudraVigilance database; TNF, tumour necrosis factor.