International Consensus Statement on an Update of the Classification Criteria for Definite Antiphospholipid Syndrome(APS)

The current treatment approach for systemic lupus erythematosus (SLE), as outlined in the recommendations by international medical associations including EULAR and the ACR, is mostly eminence-based rather than evidence-based. However, knowledge on SLE is growing quickly, and such new advances need to be translated into clinical practice. Questions remain regarding the choice and timing of drug administration and tapering until withdrawal, which both can affect the balance between the control of disease activity and damage to organs triggered by long-standing and/or disproportionate immunosuppression. Currently, the treating physicians of patients with SLE are required to weigh the present with the future situation of their patients in an optimized balance between therapeutic harm and benefit. In this Review, the available therapeutic strategies and main challenges in the approach to SLE treatment are discussed. Remission and low disease activity are desirable therapeutic goals. Although the drug armamentarium for SLE has not expanded much in the past few decades, there are nonetheless opportunities to make better choices and explore combination therapies; such opportunities offer the potential of a personalized medicine strategy. The treatment of systemic lupus erythematosus involves a balance between control of disease activity and prevention of therapeutic harm that requires careful optimization. In this Review, the authors discuss available and emerging therapeutic strategies that exploit the current drug armamentarium.

New therapeutic strategies in systemic lupus erythematosus management

OBJECTIVE Conventional treatment of systemic lupus erythematosus (SLE) and lupus nephritis (LN) is associated with damage accrual, hence increased morbidity rate. Off-label use of rituximab (RTX) has shown significant promise in this patient group; however, data are still controversial. We aimed to analyze the outcomes of RTX therapy in refractory lupus using a meta-analysis approach. METHODS Electronic search of the medical literature was conducted using a combination of relevant keywords to retrieve studies on the safety and efficacy of RTX in SLE and LN patients. Results were screened against our inclusion and exclusion criteria and two reviewers independently extracted the data for analysis. Comprehensive meta-analysis software was used to pool the data from individual studies and provide summary effect estimates. RESULTS Thirty-one studies that enrolled 1112 patients were finally eligible for the meta-analysis. The overall global, complete, and partial response rates to RTX therapy were 72%, 46%, and 32%, respectively. RTX significantly decreased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and British Isles Lupus Activity Group (BILAG) scores (p<0.001). Prednisone dose was significantly reduced after RTX treatment in both SLE and LN groups (p<0.001), and proteinuria was lowered in SLE (p<0.001) than in LN patients (p=0.07). Infection and infusion-related reactions were the most common side effects. CONCLUSION RTX therapy in refractory SLE and LN patients proved clinical efficacy and favorable safety outcomes. Larger well-designed randomized clinical trials are warranted.

Outcomes of rituximab therapy in refractory lupus: A meta-analysis.

The only case of idiopathic membranous glomerulonephritis seen out of 106 nephropathic patients biopsied in the two last years at the C. H. 20 de Noviembre, I.S.S.S.T.E., is reported. Twenty-six showed nephrotic syndrome not associated to systemic disease, including the present case, which gave us an incidence of 3.8% of this entity. We were impressed by the low frequency of this disease, so we made a statistical epidemiological analysis localizing it geographically based on the available medical literature. On comparing the results of these studies we confirmed that this disease is significantly low in our environment.

Idiopathic membranous glomerulonephritis

Systemic lupus erythematosus (SLE) is a systemic autoimmune condition characterised by a wide spectrum of clinical manifestations, partly related to the disease itself, but also linked to its comorbidities and drugs adverse reactions. Following the previous annual reviews, we focused on new insights in SLE clinical features, pathogenic pathways, biomarkers of specific organ involvement and therapeutic strategies. We finally concentrated on SLE aspects that could significantly influence patients' quality of life and that need to be investigated in detail through the development and validation of disease-specific patient-reported outcomes.

One year in review 2018: systemic lupus erythematosus.

APS is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for aPL. APS can be isolated (primary APS) or associated with other autoimmune diseases. The kidney is a major target organ in APS, and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal vasculature and renal veins). Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal involvement in patients with definite APS is treated with long-term anticoagulants as warfarin, but new treatments are being tried. The aim of this article is to review the links between primary APS and kidney disease.

Kidney disease in primary anti-phospholipid antibody syndrome.

Key Points Question Is the use of anakinra plus the standard of care effective compared with the standard of care alone in reducing the probability of requiring mechanical ventilation among patients with severe COVID-19 pneumonia? Findings In this randomized clinical trial with 179 patients, the proportion of patients not requiring mechanical ventilation up to day 15 was not significantly different between groups (77.1% for anakinra group vs 85.9% for standard of care group). Meaning This study did not find evidence of effectiveness of anakinra vs the standard of care in reducing the need for mechanical ventilation among patients with severe COVID-19 pneumonia, and future research should assess anakinra in patients with less-severe pneumonia.

/pdf/efficacy-and-safety-of-anakinra-plus-standard-of-care-for-3dij473n.pdf

Efficacy and Safety of Anakinra Plus Standard of Care for Patients With Severe COVID-19

263 The Use of Rituximab in Newly Diagnosed Systemic Lupus Erythematosus Patients: Long-Term Steroid-Saving Capacity and Clinical Effectiveness

Background Previous reports indicate that treating patients with lupus (SLE) at or close to the time of diagnosis successfully without using any, or minimal, corticosteroids by using B-cell depletion (BCD) is possible in the short-term. It is not however known whether using BCD is as effective or reduces corticosteroid use in the long-term. We report the long-term (up to 7 years) use of BCD with respect to its steroid-saving capacity and clinical effectiveness in newly diagnosed SLE. Methods Sixteen female patients with SLE were treated at, or shortly after diagnosis, with BCD therapy (BCDT) minimising the routine use of oral steroids. Post-treatment, most patients were given hydroxychloroquine (n=14) and azathioprine (n=10). The British Isles Lupus Assessment Group (BILAG) disease activity index was used for clinical assessment. Serum antidouble-stranded DNA (dsDNA) antibodies, complement (C3), erythrocyte sedimentation rate (ESR), circulating B lymphocytes (CD19 + ) and total inmmunoglobulins were tested every 2–6 months (average of 4.5 years) (SD 2) post-treatment. Disease activity and steroid requirement were compared with three patients with SLE treated conventionally, each matched for ethnicity, sex, age, clinical features, disease duration at diagnosis and follow-up period. Results All patients given rituximab achieved BCD. The mean number of flares during follow-up (new BILAG A or B) was 2.63 (SD 3) in the BCDT group and 4 (SD 3.6) in the controls (NS, p=0.14). Post-BCDT, mean anti-dsDNA antibody level fell from 1114 U/mL (SD 1699.3) to 194 (SD 346.7) at 18 months (p=0.043), mean serum ESR fell by >70% at 6 months maintained during follow-up and serum C3 level normalised in 8 patients. The mean cumulative prednisolone dose at 60 months for the patients who underwent BCDT (n=11) was 4745.67 mg (SD 6090 mg) vs 12 553.92 mg (SD 12 672 mg) for the controls (p=0.01). Conclusions Early treatment of patients with SLE with BCDT is safe, effective and enables a reduction in steroid use.

https://lupus.bmj.com/content/lupusscimed/4/1/e000182.full.pdf

The use of rituximab in newly diagnosed patients with systemic lupus erythematosus: long-term steroid saving capacity and clinical effectiveness

Identification of risk factors for permanent visual loss in patients with giant cell arteritis.

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