EULAR recommendations for the management of systemic lupus erythematosus: 2023 update

Abstract

ObjectivesTo update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.MethodsAn international Task Force formed the questions for the systematic literature reviews (January 2018–December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.ResultsThe Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual’s risk for flares and retinal toxicity. GC are used as ‘bridging therapy’ during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.ConclusionThe updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.

Efficacy of Voclosporin in Proliferative Lupus Nephritis with High Levels of Proteinuria

“…Current guidelines for the management of lupus nephritis recommend targeting a UPCR of ,0.5-0.7 g/g within 12 months of initiating treatment. 15,26 In this study, 34% of participants in the voclosporin arm achieved a complete renal response (requiring UPCR reduction to ,0.5 g/g) at Median time to event (95% CI) calculated using Kaplan-Meier methods. Participants who did not achieve the event during the 12-month study period were censored on the day of their last available UPCR assessment.…”

“…[8][9][10] Nephrotic-range proteinuria, typically defined as urine protein-creatinine ratio (UPCR) $3 g/g, has been associated with a lower likelihood of achieving complete or partial renal response in patients with lupus nephritis and an overall worse prognosis. 4,[8][9][10][11][12][13][14][15][16] Furthermore, in lupus nephritis and in other inflammatory diseases leading to CKD, higher levels of proteinuria have been associated with significantly greater and more rapid decline in eGFR over time. 4,[17][18][19][20] Proteinuria remains one of the most commonly used surrogate markers of disease activity in lupus nephritis, and early reductions in proteinuria after treatment initiation have been shown to predict improved longterm renal outcomes.…”

“…13,[21][22][23][24][25] The current European League Against Rheumatism and the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for the management of lupus nephritis are focused on lowering proteinuria, with the European League Against Rheumatism recommending a goal of $50% reduction in UPCR by 6 months and 24-hour protein of ,0.5-0.7 g with near-normal eGFR by 12 months. 15,26 Voclosporin is a second-generation calcineurin inhibitor approved in the United States, Great Britain, the European Union, and Switzerland for the treatment of adult patients with active lupus nephritis in combination with background immunosuppressive therapy. Voclosporin was developed through the addition of a single carbon extension to the amino acid-1 position of cyclosporin A.…”

Interferon-Inhibition beim systemischen Lupus erythematodes

“…Basierend auf den positiven Studienergebnissen erhielt ANI 2021 die Zulassung in den USA und 2022 in Europa. Mit dem Update der EULAR-Recommendations zum Management des SLE 2023 wird der Einsatz von ANI nun auf einer Ebene mit der Initiierung von konventionellen Immunsuppressiva und/oder BEL bei unzureichendem Ansprechen auf Hydroxychloroquin empfohlen [18]. Zwar ist ANI zur Therapie des schweren SLE zugelassen, es muss jedoch betont werden, dass die Substanz bei schweren Organmanifestationen bislang nicht untersucht wurde, sodass sich der Einsatz im schweren SLE vornehmlich auf schwere Hautmanifestationen bezieht.…”

Excellent response to treatment with hydroxychloroquine in pediatric patients with SLE‐related immune thrombocytopenia

“…[19][20][21][22] Hydroxychloroquine (HCQ), originally an antimalarial drug, has various immunomodulatory effects and plays an essential role in the treatment of SLE. 23 HCQ's main mechanism of action is increasing the PH in the acidic lysosomes and therefore interfering with metabolic and immune pathways. 24,25 Besides being the mainstay of treatment for patients with SLE, HCQ is rarely used in ITP.…”