The Monoclonal Antibody Medications in inflammatory Arthritis: stopping or continuing in pregnancy (MAMA) trial

Research Question

In pregnant women with Autoimmune Inflammatory Arthritis (AIA) (population), does continuing biological disease modifying anti-rheumatic drugs (bDMARDs) (intervention), compared with stopping bDMARDs before the third trimester of pregnancy (comparator) result in better arthritis symptom control (outcome), during and up to six months after the end of pregnancy?

Background

AIAs are devastating, potentially joint destroying conditions, affecting 1-2% of people. AIA includes rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA) and juvenile idiopathic arthritis (JIA). These AIA conditions collectively affect many women during their reproductive years, and many women with these chronic conditions wish to plan pregnancy.

The Monoclonal Antibody Medications in inflammatory Arthritis (MAMA) trial is designed to address the significant uncertainty surrounding the effects of continuing or stopping bDMARDs during pregnancy. Aims and Objectives

Aim: To investigate whether continuing bDMARDs in pregnancy compared to stopping before the third trimester is clinically and cost-effective in women with AIA and their infants.

Primary objective: To compare the peak of disease activity from randomisation up to 6 months after the end of pregnancy in pregnant women with AIA randomised to continue bDMARDs versus those randomised to stopping bDMARDs before the third trimester of pregnancy. Secondary objectives:

• To compare peak of disease activity up to 12 months after the end of pregnancy, arthritis disease activity up to 6 months after the end of pregnancy, pregnancy outcomes up to hospital discharge after the end of pregnancy and neonatal outcomes in babies.

• To investigate infant and child outcomes, including key long-term outcome of child development at 24 months of age, infections up to 24 months of age, and immune function (including response to vaccines) at 2, 5 and 13 months.

• To examine using an economic evaluation, whether any additional benefits associated with continuing bDMARDs are justified by any additional health care resources needed up to 24 months after the end of pregnancy. Methods

Design: MAMA is a multicentre, pragmatic, two-arm, parallel-group, unblinded randomised controlled trial, with an internal pilot and an integrated health economic analysis, co-designed with lived experience contributors. Intervention: Continuing bDMARDs throughout pregnancy.

Comparator: Stopping bDMARDs before the third trimester (28 weeks) of pregnancy and restarting no earlier than 2 weeks after the end of pregnancy. Setting: 35 obstetric units with a maternal medicine service. Population: Pregnant women at less than 28 completed weeks’ gestation prescribed a regularly dosed bDMARD for AIA.

Outcomes

Primary outcome: Peak disease activity as measured by highest self-reported RAPID3 score post-randomisation up to 6 months after the end of pregnancy.

Secondary outcomes: Disease activity, pregnancy, neonatal and child outcomes, economic evaluation, and woman and clinician acceptability. Sample size: 328 women (164 per trial arm) individually randomised. Timeline

Trial duration of 72 months: 6 months set up; 48 month recruitment; 12 months follow up, 6 months data collection, analysis, reporting Impact and dissemination

This will be the first adequately powered trial to assess the safety and effectiveness of the use of bDMARDs in AIA in pregnancy, for women and their children. Regardless of the trial results, MAMA will lead to more evidence-based practice and cost effective care for women with AIA in pregnancy and will provide important data in infant immune responses after in-utero biologic exposure.

We will disseminate results through journals, conferences, co-designed materials, social media and free online conferences for patients, families and healthcare professionals.