EULAR recommendations for the management of antiphospholipid syndrome in adults.

The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2-3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2-3 or INR 3-4 is recommended, considering the individual's bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3-4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.

An overlook on the current registries for rare and complex connective tissue diseases and the future scenario of TogethERN ReCONNET.

Background: Patient registries play a crucial role in supporting clinical practice, healthcare planning and medical research, offering a real-world picture on rare and complex connective tissue diseases (rCTDs). ERN ReCONNET launched the first European Registry Infrastructure with the aim to plan, upgrade and link registries for rCTDs, with the final goal to promote a harmonized data collection approach all over Europe for rCTDs. Methods: An online survey addressed to healthcare professionals and patients' representatives active in the field of rCTDs was integrated by an extensive database search in order to build a mapping of existing registries for rCTDs. Findings: A total of 140 registries were found, 38 of which include multiple diseases. No disease-specific registry was identified for relapsing polychondritis, mixed connective tissue disease and undifferentiated connective tissue disease. Discussion: This overview on the existing registries for rCTDs provides a useful starting point to identify the gaps and the strengths of registries on the coverage of rCTDs, and to develop a common data set and data collection approach for the establishment of the TogethERN ReCONNET Infrastructure.

The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET.

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies.

Management of thrombotic and obstetric antiphospholipid syndrome: a systematic literature review informing the EULAR recommendations for the management of antiphospholipid syndrome in adults.

Objective: To perform a systematic literature review (SLR) informing the European Lmmendations for the management of antiphospholipid syndrome (APS) in adults. Methods: A SLR through January 2018 was performed. Research questions were constructed using the Patient, Intervention, Comparator, Outcome (PICO) format. We included data from articles that reported on each relevant intervention. Summary effect estimates were calculated for direct comparison studies that matched the PICO question exactly, and for studies with the relevant intervention and comparator. When meta-analyses were available, we used these estimates. Results: From 7534 retrieved articles (+15 from hand searches), 188 articles were included in the review. In individuals with high-risk antiphospholipid antibody (aPL) profile without prior thrombotic or obstetric APS, two meta-analyses showed a protective effect of low-dose aspirin (LDA) against thrombosis. Two randomised controlled trials (RCTs) and three cohort studies showed no additional benefit of treatment with vitamin K antagonists at target international normalised ratio (INR) 3-4 versus INR 2-3 in patients with venous thrombosis. In patients with arterial thrombosis, two RCTs and two cohort studies showed no difference in risk of recurrent thrombosis between the two target INR groups. One open-label trial showed higher rates of thrombosis recurrences in triple aPL-positive patients treated with rivaroxaban than those treated with warfarin. RCTs and cohort studies showed that combination treatment with LDA and heparin was more effective than LDA alone in several types of obstetric APS. SLR results were limited by the indirect evidence and the heterogeneity of patient groups for some treatments, and only a few high-quality RCTs. Conclusion: Well-designed studies of homogeneous APS patient populations are needed.

Antiphospholipid syndrome: state of the art on clinical practice guidelines.

Antiphospholipid syndrome (APS) is a rare disease characterised by venous and/or arterial thrombosis, pregnancy complications and the presence of specific autoantibodies called antiphospholipid antibodies. This review aims to identify existing clinical practice guidelines (CPG) as part of the ERN ReCONNET project, aimed at evaluating existing CPGs or recommendations in rare and complex diseases. Seventeen papers providing important data were identified; however, the literature search highlighted the scarceness of reliable clinical data to develop CPGs. With no formal clinical guidelines in place, diagnosis and treatment of APS is largely based on consensus and expert opinion. Patients' unmet need refers to the understanding of the disease and its clinical picture and implications, the need of education for patients, family members and healthcare providers, as well as to the development of monitoring pathways involving multiple healthcare providers.