British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: comorbidity medications used in rheumatology practice

Background
The rationale behind this update on the 2016 BSR guidelines on prescribing anti-rheumatic drugs in pregnancy and breastfeeding [1, 2] was described in detail in the guideline scope [3]. In brief, despite the existence of additional evidence-based guidelines on prescribing/managing rheumatic disease in pregnancy [4-7] the information contained within them requires continual review to include emerging information on the safety of new and existing drugs in pregnancy.

Chronic disease adversely affects pregnancy. Data from Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK (MBRRACE-UK), reports regularly from a national programme of work conducting surveillance and investigating the causes of maternal deaths, stillbirths and infant deaths [8]. Data from 2017-19, found that 8.8 women per 100,000 died during pregnancy or up to six weeks after childbirth or the end of pregnancy, and most women who died had multiple health problems or other vulnerabilities[8]. In all decisions regarding medication choices and changes, it is also important to consider the potential for deterioration in the mother's wellbeing through side effects or reduced disease control (and its adverse impact on the baby). Therefore, the exposure of the fetus to different drugs when switches are made must be balanced against possible fetal gains, and understanding the potential impact of reduced control of the medical disorder on a pregnancy is vital [9].

Need for guideline
Patients with inflammatory rheumatic disease (IRD) should be counselled to achieve and then maintain remission or low disease activity before/during pregnancy to reduce the risk of adverse pregnancy outcomes [10]. This goal is primarily achieved through adjustment of therapy to ensure disease control with disease modifying anti-rheumatic drugs (DMARDs) and/or immunosuppressive drugs that are compatible with pregnancy. These medications are reviewed in the BSR & BHPR guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids [11]. Many patients with IRD however, have an additional burden of pain and comorbid illness [12] that require treatment with other medications. The compatibility of various comorbidity medications relevant to rheumatic disease will be covered in this update. This updated information will provide advice for healthcare professionals and patients to ensure more confident prescribing in these scenarios and will highlight any medications that should be stopped and/or avoided in the reproductive age group unless highly effective contraception is used, in line with guidance issued by the Medicines and Healthcare Products Regulatory Agency (MHRA) and Faculty of Sexual and Reproductive Healthcare [13, 14].

Objectives of guideline
To update the previous BSR guidelines on prescribing in pregnancy in rheumatic disease for the following drug categories: pain management; Non-steroidal anti-inflammatory drugs (NSAIDs) and low dose aspirin; anticoagulants; colchicine; dapsone; bisphosphonates; anti-hypertensives; and pulmonary vasodilators. This revised guideline was produced by consensus review of current evidence to answer specific questions in relation to each drug as follows. Should it be stopped pre-conception? Is it compatible with pregnancy? Is it compatible with breastmilk exposure? Where possible recommendations are made regarding compatibility with paternal exposure.

Target audience
The primary audience consists of health professionals in the UK directly involved in managing patients with rheumatic disease who are (or are planning to become) pregnant and/or breastfeeding, men planning to conceive, and patients who have unintentionally conceived whilst taking these medications. This audience includes rheumatologists, rheumatology nurses/allied health professionals, rheumatology speciality trainees and pharmacists, as well as the patients themselves. The guideline will also be useful to obstetricians, obstetric physicians, renal physicians, dermatologists and general practitioners who may prescribe these medications to patients in pregnancy.

This guideline uses the terms “woman”, “maternal” or “mother” throughout. These should be taken to include people who do not identify as women but are pregnant or have given birth [15]. Where the term “breastfeeding” is used in this guideline it also refers to infant breastmilk exposure via other methods (e.g. expressed breastmilk, administered via a bottle).

The areas the guideline does not cover
This guideline does not cover the management of infertility or acute pain relief during labour, hence morphine was excluded. Other drug categories: antimalarials; corticosteroids; disease modifying anti-rheumatic and immunosuppressive therapies; and biologic drugs are considered in another guideline (REF for part I). All recommendations in this guideline were formulated by the working group on the basis of published evidence at the time of the systematic literature search, and do not necessarily refer to licensing information or Summary of Product Characteristics for individual medications.

Stakeholder Involvement
This guideline was commissioned by the BSR Standards, Guidelines and Audit Working Group. A Guideline Working group (GWG) was created, consisting of a chair (IG), alongside representatives from relevant stakeholders (Table 1). In accordance with BSR policy, all members of the GWG made declarations of interest, available on the BSR website.

Involvement and affiliations of stakeholder groups involved in guideline development
The GWG consisted of rheumatologists from a range of clinical backgrounds, various allied health professionals, other specialists in women’s health, lay members and representatives from the United Kingdom Tetralogy Information Service (UKTIS). All members of the working group contributed to the process for agreeing key questions, guideline content, recommendations and strength of agreement.