New effective therapies during the last 15 years have improved outcome and quality of life in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA). More female patients consider pregnancy. However, adjustements of therapy before and during pregnancy are required. Classical disease modifying drugs (cDMARDs), prednisone, and non-steroidal anti-inflammatory drugs (NSAIDs) remain valid options for treatment of pregnant patients because their safety profile in regard to the fetus is known. Among cDMARDs antimalarials, sulfasalazine, azathioprine, and cyclosporine are compatible with use throughout pregnancy. Methotrexate and cyclophosphamide are teratogenic and must be discontinued before a planned pregnancy. In spite of no indication for teratogenicity in humans, child safety has still not been established for leflunomide, so a washout procedure should be completed before conception. Prolonged and high doses (>7.5 mg/day) of prednisone carry risk for side effects in mother and fetus and should be avoided during pregnancy.
In contrast to cDMARDs, child safety is a concern for new biologics with no or little pregnancy experience, and for combination therapies which include methotrexate or leflunomide. TNFα – inhibitors (TNFi) are the best studied biologics. Related to their differences in structure transplacental passage varies with high amounts of transfer in late pregnancy for monoclonal TNFi that posess a Fc part of IgG1. TNFi with either small affinity to the fetal Fc receptor or with no Fc part show low transplacental passage to the child. TNFi can be given before conception and during the first and early 2nd trimester of pregnancy. When possible Fc containing TNFi should be avoided in the third trimester. Studies that investigate child health, particularly infection rate in the first year after antenatal exposure to TNFi are in progress and will provide answers how best to use TNFi in pregnant patients.
For most other biologicals data on human pregnancy exposure are sparse. Decisions for treatment during pregnancy in regard to biologics targeting B-cells, T cell activation or cytokines like IL-6, IL-23, IL-17 or IL-1β must be based on the severity of maternal disease and have to be reserved for cases where no other safe options are available. Publications on fetal side effects or long term outcomes of in utero exposed children for rituximab, abatacept, tocilizumab, ustekinumab and anakinra are few and cannot guarantee safety for the child. They are therefore best avoided during pregnancy. In order to prevent unintended pregnancy exposure to insufficiently studied biologicals, often in combination with MTX, family planning should be discussed and counseling given on contraception to patients of fertile age.
Østensen, M, Förger, F. Management of RA medications in pregnant patients. Nat. Rev. Rheumatol 2009; 5: 382–390.
Disclosure of Interest None declared