Biologics Use for Psoriasis during Pregnancy and Its Related Adverse Outcomes in Pregnant Women and Newborns: Findings from WHO Pharmacovigilance Study

Yi Deun Jeong; Hyesu Jo; Hanseul Cho; Wonwoo Jang; Jaeyu Park; Sooji Lee; Hayeon Lee; Kyeongmin Lee; Jiyeon Oh; Xuerong Wen; Lee Smith; Dong Keon Yon

doi:10.1159/000542217

Biologics Use for Psoriasis during Pregnancy and Its Related Adverse Outcomes in Pregnant Women and Newborns: Findings from WHO Pharmacovigilance Study

Int Arch Allergy Immunol. 2024 Dec 3:1-15. doi: 10.1159/000542217. Online ahead of print.

Authors

Yi Deun Jeong^{1

2}, Hyesu Jo^{1

3}, Hanseul Cho^{1

2}, Wonwoo Jang^{1

2}, Jaeyu Park^{1

3}, Sooji Lee^{1

2}, Hayeon Lee¹, Kyeongmin Lee^{1

3}, Jiyeon Oh^{1

2}, Xuerong Wen⁴, Lee Smith⁵, Dong Keon Yon^{1

2

3

6}

Affiliations

¹ Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
² Department of Medicine, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
³ Department of Regulatory Science, Kyung Hee University, Seoul, Republic of Korea.
⁴ Department of Pharmacy Practice and Clinical Research, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA.
⁵ Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK.
⁶ Department of Pediatrics, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea.

PMID: 39626647
DOI: 10.1159/000542217

Abstract

Introduction: The safety of biologics, other than TNF-α inhibitors, during pregnancy has not been sufficiently established. To assess the risk of pregnancy-related adverse outcomes of biologics used for psoriasis, compared to TNF-α inhibitors, we utilized the WHO global pharmacovigilance database (1968-2024).

Methods: We utilized the World Health Organization's global pharmacovigilance database from 1968 to 2024. From over 140 million reports from more than 170 countries, we extracted 6,518 reports of pregnancy-related adverse outcomes associated with the biologics of interest. These biologics included TNF-α inhibitors (e.g., etanercept, infliximab, adalimumab, certolizumab pegol), IL-12/IL-23 inhibitor (e.g., ustekinumab), IL-17 inhibitors (e.g., secukinumab, brodalumab, ixekizumab, bimekizumab), and IL-23 inhibitors (e.g., guselkumab, tildrakizumab, risankizumab). Each biologic was compared to TNF-α inhibitors and certolizumab pegol in two separate disproportionality analyses. The reporting odds ratio (ROR) was calculated for maternal, fetal, and neonatal outcomes, categorized into seven major groups. Multivariable and sensitivity analyses were conducted to validate the primary results.

Results: The disproportionality analysis showed that, compared to TNF-α inhibitors, most biologics had a lower frequency of pregnancy-related adverse outcomes, with the exception of brodalumab. Specifically, ROR and 95% confidence intervals (CIs) were as follows: ustekinumab (ROR, 0.27; 95% CI: 0.21-0.35), secukinumab (0.17; 0.13-0.22), brodalumab (0.20; 0.02-2.21), ixekizumab (0.05; 0.03-0.08), bimekizumab (0.10; 0.01-0.71), guselkumab (0.09; 0.05-0.15), tildrakizumab (0.02; 0.00-0.14), and risankizumab (0.38; 0.25-0.58). However, risankizumab was reported with a higher frequency of abortion and stillbirth (1.87; 1.32-2.63). These findings were consistent when compared to certolizumab pegol, as well as in multivariable and sensitivity analyses. Furthermore, when comparing other TNF-α inhibitors to certolizumab pegol, infliximab showed a lower frequency of pregnancy-related adverse outcomes (ROR, 0.71; 95% CI: 0.55-0.92), etanercept showed a comparable frequency (1.00; 0.77-1.31), and adalimumab showed a higher frequency (1.42; 1.11-1.81).

Conclusions: Biologics used for psoriasis, with the exception of brodalumab, exhibit a lower frequency of pregnancy-related adverse outcomes compared to TNF-α inhibitors and certolizumab pegol, suggesting their potential to be safe options during pregnancy. However, further studies are necessary to evaluate the safety of these biologics during pregnancy, accounting for confounding factors.

Keywords: Adverse outcomes; Biologic; IL-12/IL-23 inhibitor; IL-17 inhibitor; IL-23 inhibitor; Pregnancy; Psoriasis; Tumor necrosis factor-alpha inhibitor; VigiBase; WHO.