Addressing the evidence gap: Arthritis treatment in pregnancy

The MAMA Study is designed to improve certainty around the treatment of inflammatory arthritis in pregnancy 

Inflammatory arthritis (IA), such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and juvenile arthritis, affects many women during their reproductive years. More women with arthritis are considering starting a family, since treatment with biologics means they are more able to manage their arthritis, with many living active lives with support from health professionals within the community.

Biologic drugs are considered safe to take in pregnancy, as the structure of biologics mean that they do not cross the placenta during the first trimester when the main foetal structural development is occurring, so there is no known association with increased miscarriages, stillbirth or abnormalities; however despite the good fetal safety profile of these medications, it remains uncertain whether biologics should be continued throughout the entire pregnancy, as many, but not all,  women find that their arthritis remains well controlled even without medication.

Should arthritis flare in pregnancy, it might mean that additional treatments, such as glucocorticoids, such as prednisolone, are needed, which also come with risks. It is also known that most biologics will cross the placenta in the third trimester, meaning that the newborn will have detectable levels of the drug. Because of this, certain vaccines, such as BCG, are contraindicated for the first 6 months of life. It is unknown whether there are any other effects on the infant immune system. 

With increasing safety evidence, in 2022, the British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids indicated that women can stay on biologics throughout pregnancy, should they or their doctors decide to continue them. Still, it’s currently unknown whether there is any benefit to this strategy in terms of arthritis disease control. Many women also remain hesitant as to whether they want to continue their medications in pregnancy if not absolutely needed. 

Women often describe anxiety around these difficult decisions. “…deciding to take medication in pregnancy made me feel guilty… it was hard feeling like I was putting my health before my baby’s…”, and “…managing RA is like walking a tightrope… it takes so long to find a drug combination that works… coming off a drug that helped me manage my symptoms was a huge decision. We were so worried about how I would manage flare-ups whilst also being pregnant. And if I came off the biologics, would I respond in the same way when I came back on them?” 

There is a lack of evidence on whether women should continue their biologic throughout the entire pregnancy or stop it at some point before the third trimester and restart it after they give birth. 

Dilemmas continue despite updated guidance, and there remains wide variation in practice across the UK. 

A 2022 national survey of obstetricians, rheumatologists, and maternal medicine specialists found only 8% of clinicians routinely continued biologics throughout pregnancy, with the exception of certolizumab (68% continue). Certolizumab is a pegolated TNF inhibitor and, as such, does not cross the placenta in any meaningful way.

Despite reassuring safety data for all five anti-TNF biologics and guidelines now suggesting that all anti-TNF biologics may be continued, the survey reported that only 38% and 42% of clinicians would prescribe etanercept or adalimumab in pregnancy, respectively. There is also variation in when rheumatologists would advise patients to stop biologics should they become pregnant, although many would “allow” their patients to continue the drug until at least the second trimester, stopping before week 28, to ensure that drug levels in the baby at birth were minimised.

Pregnancy prescribing practices for newer-generation biologic agents are still slightly guarded, given the more limited data on pregnancy outcomes with these drugs. That said, pregnant women are, however, increasingly seen at obstetric units with a maternal medicine service, taking newer generation biologics for other inflammatory conditions such as inflammatory bowel disease, with many continuing these drugs throughout pregnancy.  Therefore, there remain inconsistencies in the ways that biologics are being prescribed during pregnancy in women with arthritis in the UK.  

The Monoclonal Antibody Medications in Inflammatory Arthritis (MAMA) study is funded by the National Institute for Health and Care Research (NIHR) and designed to address this significant uncertainty and resulting variation in practice by filling the gaps in evidence. 

MAMA, aims to find out the effects of temporarily stopping or continuing biologics during pregnancy. Comparing whether women randomly allocated to continue their biologics throughout pregnancy have better arthritis control compared to those who are allocated to temporarily stop at the end of six months of gestation to restart after delivery, and assessing the impact on their pregnancy, their infant (including immune response), and the costs associated with this decision. 

MAMA is being supported by 35 NHS sites in the UK to recruit 328 women over a 48-month recruitment period. To allow all communities and regions the opportunity to take part, they are inviting all health professionals who support women who are on a biologic for inflammatory arthritis and planning a pregnancy or are pregnant, to signpost them to MAMA.

Please share these links to MAMA information with patients and colleagues:

Information for Health Professionals
Information for women

If you would like print and digital resources for your department, including posters, please complete this form.

All resources guide women to the MAMA website, where they can learn more about the study and how they can participate. Or, they can contact the MAMA Co-ordinating Team directly at mama@npeu.ox.ac.uk or on 01865 743859.

This study is funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) Programme (Reference Number NIHR153577). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Article kindly written by Professor Kimme Hyrich, Professor of Epidemiology and Honorary Consultant Rheumatologist.