Disease-modifying therapy in multiple sclerosis during pregnancy and lactation

Abstract

Multipla skleroza (MS) je demijelinizacijska bolest središnjeg živčanog sustava te se najčešće dijagnosticira u žena reproduktivne dobi. Danas je poznato da sama bolest nije ograničavajući faktor za trudnoću budući da ne utječe na plodnost, mogućnost začeća kao ni na ishod trudnoće i zdravlje djeteta. Dapače, tijekom trudnoće kod nekih se žena simptomi bolesti poboljšaju, najčešće u zadnjem tromjesečju. S obzirom na pojavu sve širih terapijskih mogućnosti, postavlja se pitanje sigurnosti lijekova tijekom trudnoće i dojenja. Nove spoznaje se još uvijek prikupljaju, a zasad najraširenija preporuka je da trudnoća mora biti planirana i u skladu s terapijom koju bolesnica trenutno uzima. Imunomodulacijska terapija primjenjuje se tijekom trudnoće samo ako potencijalna korist za trudnicu opravdava mogući rizik za plod. Pokazano je kako pravovremeno uvođenje terapije i uspješna kontrola bolesti prije trudnoće omogućavaju njen sigurniji tijek i smanjuju mogućnost relapsa nakon poroda. Korištenje interferona beta (IFN-β) i glatiramer acetata (GA) moguće je tijekom cijelog perioda trudnoće. Teriflunomid se zadržava u organizmu otprilike osam mjeseci do čak dvije godine te ako se utvrdi trudnoća, bolesnica treba proći proces ubrzane eliminacije lijeka. Navedeni lijek kontraindiciran je tijekom trudnoće i dojenja. Primjena dimetilfumarata (DMF) se također prekida tijekom trudnoće i dojenja. Žena koja planira trudnoću treba prestati koristiti fingolimod barem dva mjeseca prije trudnoće, alemtuzumab četiri mjeseca, kladribin šest mjeseci dok je za okrelizumab potreban prekid od dvanaest mjeseci. S obzirom na to da se natalizumab koristi u žena s visoko aktivnom bolesti, nakon prekida terapije može se očekivati pogoršanje simptoma. Preporuka je koristiti ga do potvrde trudnoće ili do drugog tromjesečja te potom ponovno uvesti kratko nakon poroda. Dojenje se uvijek preporuča, ali ako je u bolesnice prisutna visoka aktivnost bolesti, trebalo bi uzeti u obzir i povratak na imunomodulacijsku terapiju. Trenutno je dojenje dopušteno kod liječenja IFN-β, a po nekim radovima sigurno je i kod žena liječenih GA. Ako postoji potreba za umjetnom oplodnjom, bolesnice bi trebalo savjetovati i upozoriti o mogućem pogoršanju bolesti, s obzirom na važnu ulogu hormona u regulaciji imunološkog odgovora kod osoba s autoimunim bolestima. Liječenje relapsa bolesti kortikosteroidima smatra se sigurnim tijekom drugog i trećeg tromjesečja te tijekom dojenja. Epiduralna i spinalna anestezija nisu kontraindicirane u oboljelih od MS-a.Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and is most commonly diagnosed in women of reproductive age. It is now known that the disease itself is not a limiting factor for pregnancy, it does not affect fertility, the possibility of conception or the outcome of the pregnancy, and the health of the child. Indeed, during pregnancy, some women's symptoms improve, most often in the last trimester. Due to the introduction of ever-widening therapeutic options, the question of drug safety during pregnancy and lactation arises. New information is still being gathered, and so far, the most widespread recommendation is that the pregnancy must be planned and following the therapy that the patient is currently taking. Disease-modifying therapy is used during pregnancy only if the potential benefit to the pregnant woman justifies the potential risk to the fetus. It has been shown that timely introduction of therapy and successful control of the disease before pregnancy enables its safer course and fewer relapses after childbirth. Interferon-beta (IFN-β) and glatiramer acetate (GA) can be used during pregnancy. Teriflunomide is retained in the body for approximately eight months to as long as two years, and if pregnancy is detected, the patient should undergo a process of accelerated elimination of the drug. It is contraindicated during pregnancy and lactation. Dimethyl fumarate (DMF) is also discontinued during pregnancy and lactation. Fingolimod should be discontinued at least two months before pregnancy, followed by alemtuzumab for four months, cladribine for six months, and ocrelizumab for twelve months. Since natalizumab is used in women with highly active disease, worsening of symptoms can be expected after discontinuation of therapy. It is recommended that it should be used until pregnancy is confirmed or until the second trimester and reintroduced as soon as possible after delivery. Breast-feeding is always recommended, but if the patient has high disease activity, a return to disease-modifying therapy should also be considered. Currently, breastfeeding is permitted with IFN-β, and according to some studies, it is safe in women treated with GA. If there is a need for medically assisted reproduction, patients should be advised and warned about the possible worsening of the disease, given that there is a possibility that hormones play an important role in regulating the immune response in autoimmune diseases. Treatment of relapse with corticosteroids is considered safe during the second and third trimesters and breastfeeding. Epidural and spinal anesthesia are not contraindicated in patients with MS