Abstract Body

Antiphospholipid syndrome (APS) is an autoimmune disease mediated by the presence of antiphospholipd antibodies (aPL). These antibodies are able to provoke clotting episodes and pregnancy loss through the activation of different pathogenic pathways. Following this argument, the ideal treatment for the disease should aim to suppress or abrogate aPLs, like an immunosuppressive treatment can do. However, immediately from the 80s, it became clear that anticoagulation is the most effective treatment because it is able to directly impair the clotting of the blood, while aPLs seemed more resistant than other autoantibodies to the immunosuppressive treatments. During the following decades, the problems and difficulties linked to the prolonged anticoagulant therapy, the long term effects of the disease and of its various clinical manifestations (including catastrophic APS, CAPS, and the so-called "non-criteria manifestations") became evident. These observations prompted the scientific community to look for possible "disease-modifying drugs" as immunosuppressors distinct from the "symptomatic ones" like anticoagulants that impair the pathological process without removing the true causes of the process.

A good observation point is to look at Systemic Lupus Erythematosus (SLE) patients with APS that usually take combined immunosuppressive treatments because of their primary disease. Some of these patients were shown to become aPL negative and could withdraw anticoagulant treatment without thrombosis recurrence. At first, hydroxychloroquine (HCQ) was studied for its immunosuppressive effect on APS patients, probably taking advantage of its known antithrombotic effect, facilitating the physicians to prescribe it. HCQ was shown able to significantly decrease the aPL titers, but only in the long term (2-5 years). Belimumab is reported to decrease the aPL levels in SLE patients taking it for their disease, again after a long observation time. According to some case reports, Rituximab is effective in persistent aPL related thrombocytopenia.

Other observations on immunosuppressive treatment in APS, are related to the treatment of CAPS and microangiopathies associated to aPLs. In these conditions the use of corticosteroids and immunosuppressants (besides anticoagulants) is already included in the recommendations and guidelines. Lately also the inhibition of complement system by Eculizumab and the inhibition of the mTOR pathway by Sirolimus were suggested by experimental data and by some clinical reports.

Abstract Body

The treatment of patients with autoimmune rheumatic diseases during pregnancy is still a real challenge for the physicians because of 2 main opposite problems. In fact, the patients and their families often do not accept the drug administration during pregnancy. The future mothers sometimes even hide the disease signs to avoid treatments that they think could damage the future baby. On the other side, we now have solid evidence that disease activity during pregnancy can influence pregnancy outcomes increasing the rate of maternal and fetal complications.

In the last few years, several rheumatological national and international societies published guidelines and recommendations to help physicians in this hard task. These works, all done by internationally recognized experts, clarify that only a few drugs are clearly teratogenic (methotrexate, cyclophosphamide, and mycophenolate) and for some other drugs of recent introduction the experience in pregnancy is still limited, but most of the molecules used to treat autoimmune rheumatic diseases do not cause malformations. However, the experience of these years has shown that some drugs do not cause malformations but can cause pregnancy complications. As an example, the administration of corticosteroids at medium-high dosage particularly in the second/third trimester is linked to an increased rate of fetal growth restriction, preeclampsia, and preterm delivery and this observation has obviously conditioned the physician’s behavior. To update the existing recommendations with the inclusion of the new drugs and of the shared experience of these years in the use of old molecules, new task forces are now starting their work.