Biological agents in pregnancy

Key points

• Biologic agents are frequently used to treat inflammatory conditions in women of childbearing age.
• All biologics cross the placenta and can therefore affect the fetus.
• There is reassuring data regarding the safety of anti-TNF biological therapies in pregnancy, however there is little data around the safety of new biologics.
• Research is needed to assess the maternal and fetal outcomes of pregnancies in which the woman received non-TNF biologic agents.

Surveillance period

1st May 2022 – 31st October 2024

Background

Biological therapies are increasingly used for a wide variety of rheumatological, respiratory, neurological, dermatological and gastroenterological conditions. Biologics are commonly used to treat young women of childbearing age with a variety of inflammatory conditions. All biologics cross the placenta and can therefore affect the developing fetus(1,2). Lack of evidence has resulted in significant differences in the advice given on the use of biological agents in pregnancy and preconception, depending on speciality. Whilst there is increasingly reassuring data regarding the safety of the use of anti-TNF biological therapies in pregnancy(3-5), there remains very limited data about the safety of new biologics(6). Given that obstetricians and obstetric physicians are seeing women in antenatal clinics who are pregnant on these newer biological agents, there is a pressing need to evaluate the outcome of these pregnancies. This study will enable us to describe the incidence of pregnancies occurring in women who are on biologic therapies and the outcomes for women and their babies exposed to these agents in pregnancy. It is hoped that the study findings will inform future guidance.

Objective

To use the UK Obstetric Surveillance System (UKOSS) to describe the incidence, risk factors and outcomes of pregnant women and their babies exposed to biological therapies.

Research questions

• What is the incidence of pregnancies in which women are using non-TNF biologic agents?
• What are the outcomes of using biologic agents in pregnancy for both mother and infant?

Case definition

All pregnant women identified as having taken one of the following biological agents* for the indication of treatment of an inflammatory disorder in pregnancy**:

Natulizumab, Duplilimab, Mepolizumab, Ustekinumab, Belimumab, Rituximab, Secukinumab, Ixekizumab, Tociluzumab, Canakinumab, Anakinra, Sarilumab, Abatacept, Guselkumab, Omalizumab, Dupilumab, Mepolizumab, Vedolizumab, Rinsakizumab, Anifrolumab, and 'other' novel biological agent (excluding Etanercept, Adalimumab, Infliximab, Certolizumab and their biosimilars).

*Biological agents are special types of disease modifying drugs used for chronic medical conditions. They are agents produced by biological rather than chemical processes using biotechnology, and including proteins, sugars, nucleic acids or complex combinations of these substances.

**Any of the following conditions: Rhueumatoid arthritis, psoriatic arthritis, Still's disease or juvenile idiopathic arthritis, spondyloarthritis, inflammatory polyarthropathy, systemic lupus erythematosus, psoriasis, uIcerative colitis, Crohn's disease, severe asthma, eczema, multiple sclerosis, takayasu arteritis, microscopic polyangiitis, granulomatosis with polyangiitis (formerly Wegener's granulomatosis), eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), polyarteritis nodosa, Kawasaki disease, other systemic vasculitis.

Excluded: Any pregnant woman who was received biological agents for the indication of severe Covid-19 infection.

Funding

This study is funded through unrestricted research funding to Cathy Nelson-Piercy.

Ethics committee approval

This study has been approved by the London - Brent REC (Ref. Number: 10/H0717/20).

Lead investigators

Dr Kate Duhig, University of Manchester,

Prof Cathy Nelson-Piercy, Guys and St Thomas' Hospital NHS Trust.

Sample Data Collection Form

UKOSS Biological agents in pregnancy DCF

References

1. Tsao NW, Lynd LD, Sayre EC, Sadatsafavi M, Hanley G, De Vera MA. Use of biologics during pregnancy and risk of serious infections in the mother and baby: a Canadian population-based cohort study. BMJ Open 2019;9:e023714.
2. Kane SV, Acquah LA. Placental transport of immunoglobulins: a clinical review for gastroenterologists who prescribe therapeutic monoclonal antibodies to women during conception and pregnancy. Am J Gastroenterol 2009;104:228-33.
3. Verstappen SMM, King Y, Watson KD, Symmons DPM, Hyrich KL. Anti-TNF therapies and pregnancy: outcome of 130 pregnancies in the British Society for Rheumatology Biologics Register. Annals of the Rheumatic Diseases 2011;70:823-6.
4. Mozaffari S, Abdolghaffari AH, Nikfar S, Abdollahi M. Pregnancy outcomes in women with inflammatory bowel disease following exposure to thipurines and antitumor necrosis factor drugs: a systematic review with meta-analysis. Hum Exp Toxicol 2015;34:445-59.
5. Nieslen OH, Gubatan JM, Juhl CB, Streett SE, Maxwell C. Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2020.
6. Povlsen K, Skov K, Storgaard L, Andersen SE. [Biological disease-modifying anti-rheumatic drugs for pregnant and lactating women or male partners]. Ugeskr Laeger 2021;183.