Reachout Orthopedics - Issue 2

data and guidelines were reviewed to develop a unified approach. Methotrexate and leflunomide are completely contraindicated at conception and in pregnancy. They require specific washout periods of 3 months recommended for methotrexate and 2 years for lefluno- mide [9, 10]. An elimination protocol using cholestyramine or activated charcoal may also be used when circumstances warrant more rapid drug elimination of leflunomide such as with pregnancy [10]. Thus, we care- fully consider whether to use these agents in women of childbearing age and always stress to women on these medications the impor- tance of adequate contraception during any period of use and the withdrawal period. Steroids are considered generally safe if required in pregnancy. Fetal risks with steroids include a slight increase risk of pre- termdelivery and a small risk of oral cleft with first trimester use. There is also of course the well-known side effect profile to the mother (including increased risk of infection). Thus, we aim to use the lowest effective dose for the shortest time possible in active disease. Non- fluorinated steroids, such as prednisolone or hydrocortisone, are generally preferred as they are metabolized by the placenta and have less fetal effects. NSAIDs can contribute to the infertility and subfertility seen in RA due to anovulation [11]. Their use in early pregnancy can be associated with increased risk of miscarriage. In the third trimester, they may cause premature closure of ductus arteriosus. Tumor necrosis factor (TNF) inhibitors may be safer than previously believed al- though we should not underestimate the risks. In 2010, a 4-month-old baby died from dis- seminated BCG [12]. His 28-year-old mother was treated with infliximab [TNF alpha inhib- itor] throughout pregnancy for inflammatory bowel disease. The previously healthy infant received his BCG at 3 months of age. Yet, there is now extensive experience and guidelines to support the use of biologics around and during pregnancy. Many rheu- matologists would continue their use for at least the initial stages of pregnancy. The updated BSR guidelines advise on timing of discontinuation of TNF inhibitors in pregnancy and breastfeeding. It is impor- tant to notice the differing timelines for the different biologic agents in these guidelines. Certolizumab pegol is compatible with all three trimesters of pregnancy and has reduced placental transfer compared with other TNF inhibitors. Infliximab may be continued until 16 weeks. Etanercept and adalimumab may be continued until the end of the second tri- mester. Golimumab is unlikely to be harmful in the first trimester. If these drugs are contin- ued later in pregnancy to treat active disease, then live vaccines should be avoided in the infant until 7 months of age [9]. There is little data available for the use of non-TNFi biologics in pregnancy or breastfeeding. BSR guidelines suggest stop- ping rituximab 6 months and tocilizumab 3 months prior to conception. Unintentional exposure to anakinra or abatacept in the first trimester is unlikely to be harmful. There are no data on the use of any of these agents in breastfeeding. EULAR guidelines suggest dis- continuing tofacitinib 2 months prior to con- ception and to avoid breastfeeding while on the medication. Lactation Guidelinesconsidernumerousanti-rheumatic drugs compatible with breastfeeding. Our approach is summarized in the chart. Results From reviewing previous studies and guide- lines, we have created a joint Saint Vincent’s University Hospital/National Maternity Hospital approach to medications for RA in women of childbearing age. The table sum- marizes our approach to managing RA in and around pregnancy. Conclusions Women with active RA might have increased subfertility and infertility. Patients should be encouraged to discuss their pregnancy plans with their healthcare providers at every consul- tation. Good disease control at all stages of re- production ensures best outcomes for mother and baby. RA tends to improve during preg- nancy and flare postpartum. Consideration should be given to the treatment of disease flares during pregnancy. There are now nu- merous anti-rheumatic drug options during pregnancy and breastfeeding with more wide- spread use of anti TNF agents in this group. Compliance with ethical standards Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent: Informed consent was not required as this study was a review of the relevant literature and guidelines on the topic. References available on request Healthcare.India@springer.com Source: Murray, K.E., Moore, L., O’Brien, C. et al . Ir J Med Sci (2019) 188: 169. https://doi.org/10.1007/s11845-018-1829- 7. © Royal Academy of Medicine in Ireland 2018. DMARDs Biologics Steroids Analgesics Before pregnancy Stop MTX 3 months prior to conception Continue TNF inhibitors None/as low as possible Stop NSAIDs if difficulties in conceiving Wash out leflunomide (two years) Consider HCQ/SSZ Stop other biologics before conception Use paracetamol During pregnancy Continue HCQ/SSZ, may taper Often stopped during trimester 2 None/as low as possible Avoid NSAIDs Consider certolizumab throughout pregnancy Use paracetamol After pregnancy Continue HCQ/SSZ Avoid leflunomide, MTX if breastfeeding Aim to restart biologics within 2 weeks (consider wound healing, infection, and breastfeeding) None/as low as possible Consider restarting NSAIDs, ideally ibuprofen if breastfeeding Use paracetamol DMARDs disease-modifying anti-rheumatic drugs, MTX methotrexate, with 5 mg folic acid weekly, HCQ hydroxychloroquine, SSZ sulfasalazine (with 5 mg folic acid daily), TNF tumor necrosis factor, NSAIDs non-steroidal anti-inflammatory drugs Compatible with breastfeeding Inadequate data about lactation Contraindicated while breastfeeding Corticosteroids TNF inhibitors Methotrexate NSAIDs Abatacept Leflunomide Hydroxychloroquine Anakinra Sulfasalazine a Rituximab Azathioprine Tocilizumab Tofacitinib a Concerns with prematurity, glucose-6-phosphate deficiency, and hyperbilirubinemia 11 reachOut Orthopedics