Exposure to biological therapies during conception and pregnancy: a systematic review. (14th December 2017)

• Record Type: Journal Article
• Authors: Pottinger, E.; Woolf, R.T.; Exton, L.S.; Burden, A.D.; Nelson‐Piercy, C.; Smith, C.H.
• Is Part Of: British journal of dermatology. Volume 178:Number 1(2018)
• Page Start: 95
• Page End: 102
• Publication Date: 2017-12-14
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.15802
• Languages: English
• ISSNs: 0007-0963

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. Abstract : What's already known about this topic? Psoriasis is common in young adults and may require treatment with a biological agent. Biologics are derivatives of human immunoglobulin G and are transported across the placenta in the second and third trimesters. Regulatory authorities state that there are no adequate studies to evaluate drug safety at conception or during pregnancy and advise against their use. What does this study add? We report a trend towards drug‐specific harm with tumour necrosis factor‐α inhibitor (TNFi) exposure in women with chronic inflammatory diseases, which manifested as increased risk of congenital malformations and preterm birth. This risk was low and did not reach statistical significance in all studies or across all outcomes. There is uncertainty over whether this risk is directly attributable to TNFi. Ongoing pharmacovigilance is required to accurately ascertain the potential effect of biologics on pregnancy outcomes specifically in women with psoriasis. Linked Comment: Hyrich. Br J Dermatol 2018; 178 :18–19 . Plain language summary available online