IMUNOMODULATORNA REUMATOLOŠKA TERAPIJA I NESTEROIDNI ANTIREUMATICI PRIJE ZAČEĆA, U TRUDNOĆI I DOJENJU – PREGLED SMJERNICA

Kristina Frketić Marović

The course and outcome of pregnancy can be affected by the activity of the inflammatory rheumatic disease itself and by the drugs we use. Evidence on the safe use of drugs during pregnancy is largely lacking due to the observational nature of the studies conducted and the difficulty of conducting clinical trials in pregnancy. The current guidelines of the professional and scientific societies of rheumatology — the European Alliance of Associations for Rheumatology (EULAR), the American College of Rheumatology (ACR) and the British Society for Rheumatology (BSR) are analysed and consolidated in this review paper. Drugs like methotrexate, leflunomide, mycophenolate mofetil, cyclophosphamide and Janus kinase inhibitors (JAK inhibitors) are contraindicated in pregnancy and should be avoided during pregnancy planning and replaced by drugs that are compatible with pregnancy. Immunomodulators that are considered compatible with pregnancy are prednisone, hydroxychloroquine, sulfasalazine, azathioprine, cyclosporine, tacrolimus, colchicine, dapsone and most biologic drugs. When it comes to biologics, tumour necrosis factor inhibitors (TNF-inhibitors) are
the most studied drugs and all of them are safe to use in the first and second trimesters of pregnancy. Certolizumab is considered to be the safest due to almost no placental transfer. There is still insufficient evidence for other biologic drugs, and it is recommended to discontinue them before pregnancy/when pregnancy is confirmed. The use of all biologic drugs can be continued throughout the pregnancy if they are necessary to establish control over the activity of the mother’s severe/life-threatening disease. Effective drug treatment of an active inflammatory rheumatic disease is possible with reasonable safety for the mother and the foetus/child during pregnancy and lactation nowadays.

Upalne reumatske bolesti na različite načine mogu utjecati na tijek i ishod trudnoće, kako zbog aktivnosti same bolesti, tako i zbog lijekova koje primjenjujemo. Dokazi o sigurnoj upotrebi lijekova tijekom trudnoće uglavnom su manjkavi zbog opservacijske prirode studija i poteškoća u provođenju kliničkih ispitivanja u trudnoći. U ovom preglednom radu analizirane su i objedinjene aktualne smjernice reumatoloških stručnih društava – European Alliance of Associations for Rheumatology (EULAR), American College of Rheumatology (ACR) i British Society for Rheumatology (BSR). Metotreksat, leflunomid, mofetilmikofenolat, ciklofosfamid i inhibitori janus kinaze (JAK-inhibitori) kontraindicirani su u trudnoći te ih treba kod planiranja trudnoće isključiti i zamijeniti kompatibilnim lijekom. Imunomodulatorni lijekovi koji se smatraju kompatibilnima s trudnoćom jesu prednizon, hidroksiklorokin, sulfasalazin, azatioprin, ciklosporin, takrolimus, kolhicin, dapson te većina bioloških lijekova. Inhibitori faktora tumorske nekroze (TNF inhibitori) najbolje su proučeni i svi se smatraju sigurnima u prvom i drugom tromjesečju trudnoće, a certolizumab se smatra najsigurnijim i gotovo bez placentalnog prijenosa kroz sva tri tromjesečja. Za ostale biološke lijekove još uvijek nema dovoljno dokaza i preporučuje ih se prekinuti prije/kod potvrđene trudnoće. Svi biološki lijekovi mogu se nastaviti uzimati kroz čitavu trudnoću ako su potrebni za kontrolu aktivnosti teške/životno ugrožavajuće bolesti majke. Aktivnu upalnu reumatsku bolest danas je uglavnom moguće učinkovito liječiti uz razumnu sigurnost za majku i za plod/dijete tijekom trudnoće i dojenja.