Controversies in the Management of Antiphospholipid Syndrome.

ABSTRACT: Strategies to prevent thrombosis in antiphospholipid antibody (aPL)-positive patients are of the utmost importance. The risk of thrombosis in patients with aPLs varies, depending on additional venous thrombosis and cardiovascular risk factors, as well as associated comorbidities. Recurrent thrombosis despite treatment with vitamin K antagonists is relatively common in daily practice. In this context, the effectiveness of the new direct oral anticoagulants in antiphospholipid syndrome is debated, as well as that of low-dose aspirin for primary thromboprophylaxis. There is an urgent unmet need to recognize the subgroup of patients that may benefit from low-dose aspirin use. Here we also discuss different points of view on primary and secondary thrombosis preventions in aPL-positive patients, which were presented as a debate during the 2021 PANLAR Congress (Pan-American League of the Association of Rheumatology) and that was organized by GESAF (Argentine Society of Rheumatology APS Study Group). It is the intention of this article to provide a useful discussion to aid treatment decision-making in daily clinical practice.

Controversies in Systemic Lupus Erythematosus 2021: Changing the Paradigm in the Management of Lupus Nephritis.

ABSTRACT: Lupus nephritis (LN) affects about a third of patients with systemic lupus erythematosus. Although the use of conventional therapy has significantly improved the prognosis of LN, the response to treatment remains suboptimal, with high rates of relapse and the occurrence of end-stage kidney disease. The implementation of new diagnostic and treatment strategies aimed at improving these outcomes represents a necessary paradigm shift in the management of LN.Herein, we discuss different points of view regarding these still unresolved issues; these comments represent a debate that took place during the virtual congress of the Pan American League of Associations for Rheumatology (PANLAR) and which was organized by the PANLAR Lupus Study Group, GLADEL (Grupo Latino Americano De Estudio del Lupus) on August 15, 2021.

Controversies in Systemic Lupus Erythematosus: Are We Treating Our Patients Adequately?

ABSTRACT: Systemic lupus erythematosus (SLE) is characterized by great clinical heterogeneity. The objectives of its management are to make a timely diagnosis and to initiate treatment as promptly as possible so organ damage can be avoided while at the same time exposure to potentially toxic drugs is minimized so that its overall course and outcome improve. In reviewing the current literature, it became quite clear that there are specific topics in which controversies do exist. These include how to treat patients with incomplete lupus erythematosus, the real possibility of abandoning altogether the use of oral glucocorticoids, and the pros and cons of the use of cyclophosphamide and mycophenolate mofetil for the induction treatment of lupus nephritis. Herein we discuss different points of view regarding these still unresolved issues; these comments represent a debate that took place during the PANLAR Virtual Congress (Pan American League of Associations for Rheumatology) and that was organized by the PANLAR Lupus study group, GLADEL (Grupo Latino Americano De Estudio del Lupus) on September 19, 2020.

A longitudinal multiethnic study of biomarkers in systemic lupus erythematosus: Launching the GLADEL 2.0 Study Group.

Introduction: After more than 20 years of sustained work, the Latin American Group for the Study of Lupus (GLADEL) has made a significant number of contributions to the field of lupus, not only in the differential role that race/ethnicity plays in its course and outcome but also in several other studies including the beneficial effects of using antimalarials in lupus patients and the development of consensus guidelines for the treatment of lupus in our region. Methods: A new generation of "Lupus Investigators" in more than 40 centers throughout Latin America has been constituted in order to continue the legacy of the investigators of the original cohort and to launch a novel study of serum and urinary biomarkers in patients with systemic lupus erythematosus. Results: So far, we have recruited 807 patients and 631 controls from 42 Latin-American centers including 339 patients with SLE without renal involvement, 202 patients with SLE with prevalent but inactive renal disease, 176 patients with prevalent and active renal disease and 90 patients with incident lupus nephritis. Conclusions: The different methodological aspects of the GLADEL 2.0 cohort are discussed in this manuscript, including the challenges and difficulties of conducting such an ambitious project.

Glucocorticoids in Systemic Lupus Erythematosus. Ten Questions and Some Issues.

Since the discovery of glucocorticoids (GCs), their important anti-inflammatory effect, rapid mechanism of action, low cost, and accessibility have made them one of the mainstays of treatment for Systemic lupus erythematosus (SLE). Although their use has allowed controlling the disease and reducing acute mortality in severe conditions, the implementation of a scheme based on high doses for long periods has inevitably been accompanied by an increase in adverse effects and infections, including long-term damage. The objective of this review is to answer some important questions that may arise from its use in daily clinical practice, and to propose a paradigm based on the use of methylprednisolone pulses followed by medium-low doses and a rapid decrease of prednisone.

Adipokines, Cardiovascular Risk, and Therapeutic Management in Obesity and Psoriatic Arthritis.

Psoriatic arthritis is a chronic inflammatory disease with skin and joint pathology as the dominant characteristics. Scientific evidence supports its systemic nature and relevant relationship with obesity, metabolic syndrome, and associated conditions. Metabolic syndrome and obesity share common signaling pathways with joint inflammation, reinforcing the idea that adipose tissue is a major contributor to disease development and severity. The adipose tissue is not a mere energy store but also an endocrine organ participating in the immune response. In the search for the best therapeutic strategy for a patient, we should appraise the adipose tissue as an endocrine and immune organ responsible for mild chronic inflammation. Today, our challenge is not only to achieve disease remission but to control the associated comorbidities as well. In light of the high prevalence of obesity in psoriatic arthritis patients and the importance of the adipose tissue in the development of chronic inflammation, we aimed to identify the most relevant articles in this regard published in English until June 2020 using the PubMed database. Search terms included psoriatic arthritis, in combination with metabolic syndrome, obesity, adipokines, cardiovascular disease, and treatment. This review summarizes the current evidence regarding the role of adipose tissue as an adipokine-secreting endocrine organ, discussing its influence on disease development and severity, and ultimately in meeting successful disease management.

Repeated pulses of methyl-prednisolone with reduced doses of prednisone improve the outcome of class III, IV and V lupus nephritis: An observational comparative study of the Lupus-Cruces and lupus-Bordeaux cohorts.

OBJECTIVE: To compare the clinical course of patients with class III, IV and V lupus nephritis (LN) treated at Hospital Universitario Cruces (CC) and at Bordeaux University Hospital (BC). METHODS: The Lupus-Cruces nephritis protocol combines pulses of 125mg of methyl-prednisolone with each fortnightly pulse of cyclophosphamide and prednisone ≤30mg/day with tapering over 12-14weeks until 2.5-5mg/day. The BC followed international lupus nephritis guidelines, combining high-dose prednisone and either mycophenolate mofetil or cyclophosphamide, followed by maintenance therapy with low dose prednisone and immunosuppressive drugs. The main outcomes were complete renal remission (CR) and glucocorticoid toxicity. RESULTS: 44 patients from BC and 29 from CC were included. The mean maximum prednisone dose was 42.5 (BC) vs. 21mg/day (CC), p<0.001. The average 6-month prednisone dose was 21 (BC) vs. 8.3mg/d (CC), p<0.001.The mean number of methyl-prednisolone pulses was 3 (BC) vs. 9.3 (CC), p<0.001. HCQ was used by 64% (BC) vs. 100% (CC), p<0.001. CR rates were 30% (BC) vs. 69% (CC), p=0.001, and 42% (BC) vs. 86% (CC), p<0.001, at 6 and 12months, respectively. Patients from the CC more frequently achieved CR (adjusted HR 3.8, 95%CI 2.05-7-09). The number of pulses of methyl-prednisolone were associated with CR (adjusted HR 1.09, 95%CI 1.03-1.15). Patients in the CC had a lower risk of GC-related side effects (adjusted HR 0.19, 95%CI 0.04-0.89). CONCLUSION: The Lupus-Cruces nephritis protocol improves the outcome of LN. Repeated methyl-prednisolone pulses help reduce the dose of oral glucocorticoids and enhance clinical response.