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

Abstract

ObjectiveDescribe available data on birth defects and pregnancy loss in women with systemic lupus erythematosus (SLE) exposed to belimumab.MethodsData 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.ResultsAmong 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.ConclusionsObservations 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.

Expert Perspective on a Clinical Challenge: Lupus and Pregnancy

“…The neonatal Fc receptor (FcRn) actively transports IgG across the placenta during pregnancy, beginning in the second trimester and increasing throughout pregnancy. Although safety data for use in pregnancy are limited, they are largely reassuring, and these medications do not appear to be teratogenic 83,84 . Nonetheless, risk of persistent immunosuppression in the infant is of concern, 85 and live‐attenuated vaccinations may need to be delayed.…”

“…Although safety data for use in pregnancy are limited, they are largely reassuring, and these medications do not appear to be teratogenic. 83,84 Nonetheless, risk of persistent immunosuppression in the infant is of concern, 85 and live-attenuated vaccinations may need to be delayed.…”

Aktuelles zu Schwangerschaften bei entzündlich-rheumatischen Erkrankungen

“…Leider konnte das BEL-Schwangerschaftsregister (BPR) nur wenige Schwangerschaften rekrutieren (55 statt der angestrebten 500). Eine aktuelle Analyse fasst Daten aus klinischen Studien, dem BPR und Spontanmeldungen deskriptiv zusammen [16].…”

Systemic lupus erythematosus: one year in review 2024

“…Therefore, these data from real-clinical settings suggest a possible role of belimumab as add-on therapy in refractory lupus nephritis in patients of Asian ancestry. About belimumab exposure during pregnancy, a descriptive summary of data from clinical trials, belimumab pregnancy registry(69), and postmarketing/spontaneous reports has been published(70). Available records about birth defects and miscarriages in belimumab-exposed pregnancies were reported.…”