Biologics considered safe for asthma during pregnancy
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Key takeaways:
- Asthma increases risks for poor outcomes in pregnancy.
- Omalizumab had no impact on live births, gestational age or congenital abnormality.
- Shared decision-making is recommended before initiating treatment.
BOSTON — The use of biologics to treat asthma during pregnancy “is very likely safe,” but the choice should follow shared decision-making, S. Shahzad Mustafa, MD, said during his presentation at the CHEST Annual Meeting.
“It’s a risk-benefit discussion between yourself, your patient in front of you, and the family,” Mustafa, chief of allergy, immunology and rheumatology at Rochester Regional Health, said. “Asthma, in and of itself, is a risk factor for poor outcomes in pregnancy.”
Compared with patients who are pregnant without asthma, risk ratios for poor outcomes among patients who are pregnant with asthma include 1.46 for low birth weight, 1.54 for preterm birth, 1.22 for small for gestational age and 1.54 for preeclampsia.
Other risk ratios include 1.39 for gestational diabetes, 1.31 for Caesarean delivery, 1.11 for congenital malformations, 1.25 for perinatal mortality and 1.5 for neonatal hospitalization.
“You have an exacerbation? That further increases your risk for these things,” Mustafa said.
Compared with patients who are pregnant with no exacerbations, odds ratios for poor outcomes among patients with exacerbations include 3.36 for low birth weight, 1.69 for preterm birth, and 1.26 for small for gestational age.
“If you have moderate to severe asthma, that further increases your risk,” he continued.
Odds ratios for poor outcomes among patients who are pregnant with moderate to severe asthma include 1.12 for low birth weight and 1.17 for small for gestational age, compared with patients who are pregnant with mild asthma.
Allergists may use systemic steroids to manage asthma, but progesterone increases during pregnancy, “and progesterone and steroids don’t get along very well,” Mustafa said. “You don’t want to be disrupting progesterone homeostasis, and that’s what steroids do.”
When progesterone and glucocorticoids are at disequilibrium, patients may experience a dysregulated endometrial immune profile, premature labor, mature activated protein C, inflammation, placental insufficiency and impaired immune ontogeny.
Although data are sparse, Mustafa continued, biologics offer safer options for patients who are pregnant. For example, the EXPECT Registry included 230 females with asthma who were treated with omalizumab (Xolair; Genentech, Novartis) while pregnant.
Compared with 1,153 pregnancies among females with asthma in the Quebec External Comparator Cohort (QECC) who did not use omalizumab, EXPECT had similar rates of live births (99.3% vs. 99.1%), gestational age (39 weeks vs. 39 weeks) and major congenital abnormality (8.9% vs. 8.1%).
Low birth weight rates included 13.7% for EXPECT and 9.8% for QECC. Small for gestational age rates included 9.7% for EXPECT and 15.8% for QECC. Premature birth rates included 15% for EXPECT and 11.3% for QECC.
“There’s really very little downside in using omalizumab,” Mustafa said. “For some of the outcomes, there’s actually some improvement.”
Mustafa advised physicians to be thoughtful when discussing treatment.
“We’re worried about risks with the medication, but there’s endogenous risks with the condition we’re treating also,” he said. “To hit that balance, I think that’s sometimes difficult to do in this space.”
Mustafa also noted a study of approximately 37,000 adverse drug reactions among patients with asthma who used dupilumab (Dupixent; Regeneron, Sanofi), including 36 involving pregnancy, puerperium and perinatal adverse drug reactions.
“There’s absolutely no safety signal, no increased odds risk, no relative risk, no increase in poor outcomes during pregnancy,” Mustafa said.
Odds ratios included 0.57 for spontaneous abortion, 0.27 for pre-eclampsia, 0.17 for ectopic pregnancy, 0.46 for neonatal jaundice, 1.12 for preterm premature rupture of membranes and 21.66 for heterotopic pregnancy.
Mustafa attributed the high odds ratio for heterotopic pregnancy to a single case.
“That threw off the confidence interval,” he said.
Additional case reports including three patients on mepolizumab (Nucala, GSK), two on benralizumab (Fasenra, AstraZeneca), and seven on dupilumab indicated acceptable outcomes with use during pregnancy as well.
Still, Mustafa said, physicians should be mindful that all biologics cross the placenta, although there has been no evidence of fetal harm in extensive animal models.
“These things do behave with linear kinetics, so they increase over time,” he said.
Mustafa also advised physicians to discuss biologics with all their female patients of childbearing age, not just those who are already pregnant.
“This is actually a conversation we should be having, maybe sooner than later,” he said.
Mustafa cited a consensus report in Lancet Respiratory Medicine agreeing that patients of childbearing age should have documented discussions with their providers about the risks and benefits of using biologics for asthma during pregnancy before beginning treatment.
“It’s all going to come down to shared decision-making,” he said.
Reference:
Naftel J, et al. Lancet Respir Med. 2024;doi:10.1016/S2213-2600(24)00174-7.