Exposure to Biological Therapies During Conception and Pregnancy

A Systematic Review

E. Pottinger; R.T. Woolf; L.S. Exton; A.D. Burden; C. Nelson-Piercy; C.H. Smith

Disclosures

The British Journal of Dermatology. 2018;178(1):95-102. 

In This Article

Methods

This systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.[18]

Selection Criteria

The aim of the review was to investigate outcomes in women exposed to biological therapies relevant to the treatment of psoriasis at conception and/or during pregnancy to assess the impact of such exposure. Relevant articles were identified using a predefined search strategy, with inclusion and exclusion criteria predefined as outlined in the study protocol (Table S1 and Table S2; see Supporting Information). Population-based cohort studies or clinical trial data were eligible for review which evaluated pregnancy outcomes in women exposed during conception or pregnancy to biological therapies relevant to the treatment of psoriasis. The primary outcome measures of adverse pregnancy outcomes that were predefined as critical for inclusion were: congenital malformations, live birth rate/still births, admission to neonatal intensive care and maternal death. Biologic included in the search strategy were TNFi (adalimumab, etanercept and infliximab), interleukin (IL)-12/23 antagonists (ustekinumab) and IL-17A antagonists (secukinumab and ixekizumab).

Included studies must have included a comparison cohort and undergone multivariate analyses of potential confounders. Unadjusted observational studies, case series or case reports were excluded. This was based on the difficulty of inferring an association between exposure and outcome with this type of data. Due to the paucity of studies with multivariate adjustment and the heterogeneity associated with the confounders included by each study, we included studies with any adjustment for appropriate confounders as defined by the study authors. This was a pragmatic decision in order to maximize the number of included studies without undermining our ability to make appropriate inferences regarding the association between biologics exposure and pregnancy outcome. Given the limited data regarding the use of biologics in pregnancy we included studies conducted in women with a range of other chronic inflammatory conditions (i.e. indirect populations) meeting these criteria.

Search Strategy and Study Screening

The search was conducted in PubMed, MEDLINE, Embase and Cochrane databases (from 1995 to August 2016) (Table S2). Duplicates were removed, titles reviewed and irrelevant studies excluded (L.S.E.). Studies reported in a language other than English were excluded. Selected articles were subsequently screened (titles and abstracts) independently using the predefined inclusion and exclusion criteria (Table S1; see Supporting Information) (C.H.S. and C.N-P.). The full-text articles were then obtained, read and re-checked against the protocol (L.S.E. and E.M.P.), with those that met the criteria distributed among the coauthors for detailed appraisal. In addition, relevant pharmaceutical companies were invited to share evidence from pharmacovigilence databases.

Quality Assessment, Data Extraction and Data Analysis

The methodological quality of the selected evidence was classified as 'very low', 'low', 'moderate' or 'high', using an adaptation of the grading of recommendations assessment, development and evaluation (GRADE) toolbox (E.M.P.).[19] This was based on an assessment of the risk of bias, inconsistency, indirectness of evidence, imprecision and publication or reporting bias. Data were extracted and summarized into tabular format using a standardized data extraction tool (E.M.P.) and subsequently verified by double extraction (R.T.W.).

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