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

Comment on:Belimumab use during pregnancy: a summary of birth defects and pregnancy loss from belimumab clinical trials, a pregnancy registry and postmarketing reports“.
Petri M, et al. Ann Rheum Dis 2022;0:1–9. doi:10.1136/annrheumdis-2022-222505

Commented by: Angela Tincani, Rheumatology and Clinical Immunology, ASST-Spedali Civili and University of Brescia, Italy

Pregnancy is a hot problem in women affected by SLE because they are usually young and therefore often expecting to have a family but also because pregnancy can have an unsuccessful outcome and can be linked to disease flares. For these reasons, drugs to be used to control the disease without affecting the fetus development are today certainly an unmet need.

Belimumab is one of the few new drugs introduced in the SLE treatment and data on its use in pregnancy generate a great expectance.

The paper collects information on 319 belimumab exposed pregnancies: 110 from clinical trials (with additional 16 exposed to placebo), 56 from the Belimumab Pregnancy Registry (BPR), 137 from spontaneous post marketing reports. Birth defects were reported among livebirths and pregnancy losses data excluded the elective terminations.

Among the pregnancy occurring in clinical trials, malformations were reported in 4/72 (5.6%) Belimumab exposed and 0/9 placebo exposed women; pregnancy losses were 35/110 (31.8%) in the Belimumab arm and 7/16 (43.8%) in the placebo arm.

The BPR reported prospective and retrospective data in 48 and 8 pregnancies respectively. The malformation rate was 21.7% and 4.2% in the 2 categories, while the occurring pregnancy losses were 4.2% and 50.0%.

Among the 137 spontaneously reported pregnancies, malformations were reported in 1/92 (1.1%) and losses in 43/137 (31.4%).

Unfortunately, the lack of a comparable disease control group, the presence of concurrent medications, the different exposure time and the often-insufficient data on birth defects do not allow to draw conclusions on the eventual Belimumab responsibility in their occurrence. In addition, the list of described birth defects include one case of congenital heart block that is known to be linked to maternal anti Ro/SS-A and /or anti La /SS-B antibodies. Finally, a consistent pattern of birth defects could not be identified.

On the other hand, it is well known that SLE itself carries many risk factors for pregnancy loss. Among them the presence of antiphospholipid antibodies and disease activity (that also could require an effective treatment such as Belimumab) are the most frequent.   But the clinical data necessary to verify the disease related risk factors were not systematically collected in the exposed cases. Consequently, the paper cannot say if Belimumab administration per se is linked to an increase rate of pregnancy losses.

In conclusion, analyzing different available sources, the paper collects all the published pregnancies exposed to Belimumab up to 8 March 2020. Even if the scarcity and heterogeneity of data do not allow to draw recommendations about the use of the drug in pregnancy, at least this publication shows that several physicians decided to administer or to maintain Belimumab during pregnancy certainly considering the risk/benefit balance. This supports the need of proper studies designed to collect clinical data and pregnancy outcome of SLE patients exposed to drugs particularly if relatively new.