Biološka terapija i trudnoća – iskustvo tercijarnog centra

Marija Bakula, Paula Kilić, Mislav Cerovec, Miroslav Mayer, Branimir Anić

Treatment of inflammatory rheumatic diseases and control of disease activity have considerably improved after the introduction of biologic therapy over a decade ago. The safety profile of biologic therapy in the preconception period as well as during pregnancy and lactation is neccessary to consider when planning the treatment of young female patients. Neither the Food and Drug Administration Agency nor the European Medicines Agency have declared biologic therapy safe during pregnancy. Both the European League Against Rheumatism and the British Society for Rheumatology proposed guidelines for the treatment of female rheumatology patients during pregnancy and lactation, and the American College of Rheumatology is currently developing guidelines for the therapeutic approach during pregnancy. On the other hand, there are numerous publications of pregnancy outcomes in patients treated with biologic therapy, with a small number of adverse effects. We analyzed the modalities of biologic therapy and pregnancy outcomes in patients treated at our Department, during planned and unplanned pregnancies. Our results do not differ from the literature published to date. Among the patients described here, 15 were treated with an inhibitor of tumor necrosis factor-α and one with an IL-6 inhibitor during or just before pregnancy. Only 2 patients stopped biologic therapy in compliance with the guidelines. Of the 16
aforementioned patients, 3 had to undergo medically-induced abortion; one patient because of a severe fetal malformation and the other two patients because they had been treated with conventional disease-modifying antirheumatic drugs, which are contraindicated during pregnancy.

Biološka se terapija primjenjuje u liječenju upalnih reumatskih bolesti posljednjih desetak godina čime se znatno unaprijedila kontrola aktivnosti bolesti. Sigurnost primjene biološke terapije u pretkoncepcijskom razdoblju te tijekom trudnoće i laktacije veoma je važna pri planiranju liječenja mladih bolesnica. Ni Američka agencija za hranu i lijekove ni Europska agencija za lijekove do danas nisu nijedan biološki lijek proglasile sigurnim u trudnoći. Europska liga protiv reumatizma i Britansko reumatološko društvo predložili su smjernice za liječenje reumatoloških bolesnica tijekom trudnoće i laktacije, dok Američko reumatološko društvo trenutačno izrađuje smjernice za terapijski pristup u trudnoći. S druge strane, objavljeni su mnogi radovi o ishodima trudnoća u bolesnica liječenih inhibitorima faktora tumorske nekroze i drugom biološkom terapijom, s malim brojem neželjenih ishoda. Cilj je ovog rada bila analiza primjene biološke terapije u bolesnica koje su planirano ili neplanirano zanijele za vrijeme liječenja u našoj ustanovi te ishoda tih trudnoća. Naši se rezultati ne razlikuju od dosad objavljene literature. Petnaest prikazanih bolesnica primalo je jedan od blokatora tumorske nekroze-α, a jedna bolesnica blokator interleukina-6 tijekom trudnoće ili neposredno prije začeća. Samo su dvije bolesnice poštovale preporučeni minimalni period od obustave terapije do začeća. Od navedenih 16 bolesnica 3 su imale medicinski indiciran prekid trudnoće: jedna zbog teške malformacije ploda, a dvije zbog terapije konvencionalnim lijekovima koji modificiraju bolest, a kontraindicirani su u trudnoći.