Exposure to biological therapies during conception and pregnancy: a systematic review

Abstract

Summary Background Biological therapies are effective treatments for psoriasis and are often prescribed to women of child‐bearing age. Objectives To evaluate the safety of biological therapy in conception and/or pregnancy. Methods We performed a systematic review of PubMed, MEDLINE, Embase and Cochrane databases for multivariate‐adjusted studies of women exposed to biologics relevant to the treatment of psoriasis during conception and/or pregnancy. Results We identified four population‐based cohort studies involving 1300 women exposed to tumour necrosis factor (TNF)‐α inhibitors (TNFi) 3 months prior to or during the first 3 months of pregnancy. These studies showed a trend towards drug‐specific harm with TNFi exposure in women with different inflammatory diseases, with an increased risk of congenital malformations [three studies; odds ratio (OR) range 1·32–1·64] and preterm birth (one study; OR 1·69, 95% confidence interval 1·10–2·60). This trend did not reach statistical significance in all studies; study heterogeneity, variation across comparator cohorts, inadequate adjustment for important confounding variables such as co‐therapy, and an absence of a common constellation of malformations means there is uncertainty about the causal role of TNFi. No studies specifically addressed the effect of TNFi exposure in psoriasis during conception and/or pregnancy, or of interleukin (IL)‐17 and IL‐12/23 antagonists in any indication. Conclusions When counselling women these findings must be balanced against the potential impact of untreated severe psoriasis on conception and/or pregnancy and maternal wellbeing; ongoing pharmacovigilance via registries remains essential to address this evidence gap.

Drug safety in pregnancy: review of study approaches required by regulatory agencies

“…This data-quality discussion may apply to studies on other diseases, and the authors cite examples of successful disease pregnancy registries for other conditions. An unrelated research group advocated for a disease registry as the best-positioned design to collect information on the preconceptional course and severity of underlying chronic inflammatory diseases for studies on drug safety in pregnancy [17]. On the other hand, another group of researchers expressed the need for an international multiproduct pregnancy exposure registry for monoclonal antibodies for any indication [18]; this registry would include some but not all treatments for MS. Our group conducted a literature review that identified studies on the safety of MS treatments in pregnancy and identified 43 publications from product-specific pregnancy exposure registries, disease registries, database studies and studies with other approaches [19].…”

The Use and Safety of TNF Inhibitors during Pregnancy in Women with Psoriasis: A Review

“…Until recently, there has been no clear evidence found of increased adverse pregnancy and birth outcome in women with psoriasis [ 10 ]. Unfortunately, these studies did not stratify for drug use, thus the effect of medication on pregnancy outcomes were not considered [ 7 , 10 ].…”

“…Most TNFi safety studies have been conducted in indirect populations, such as women with IBD and rheumatoid arthritis, consequently no studies specifically address TNFi potential risk of harm in pregnant women with psoriasis or the outcomes in their infants [ 7 ].…”

“…The most recent systematic review found a trend towards drug-specific harm with increased risk of major congenital malformations and preterm birth in infants of women with other chronic inflammatory diseases than psoriasis exposed to TNFi [ 7 ]. Supporting these findings, a Scandinavian register-based cohort study found a non-significantly higher risk of congenital malformations among women with IBD treated with TNFi.…”

“…Knowledge of safety of TNFi during pregnancy is limited but expanding [ 7 ]. It is ethically unsound to include pregnant women in randomized controlled trials investigating drug safety.…”