New therapies require a 'conceptual shift' in the treatment paradigm, say experts.
The American College of Rheumatology has released a summary of its new guideline for the screening, treatment and management of lupus nephritis.
This guideline represents the college’s first update on lupus nephritis since 2012, offering comprehensive, evidence-based recommendations for both adults and children. The full document is due to be published in 2025.
The summary document underscores the importance of collaborative care and shared decision-making between healthcare providers and patients to effectively manage lupus nephritis and its complications while minimising medication-related toxicities.
Professor Lisa Sammaritano, lead author on the guideline, presented the summary at ACR Convergence 2024 in Washington this week.
“At the time the ACR released its last lupus nephritis clinical practice guidelines, recommendations called for induction therapy with high-dose glucocorticoids plus immunosuppressant medications like mycophenolate mofetil or cyclophosphamide and endorsed mycophenolate for maintenance therapy,” said Professor Sammaritano, who is professor of clinical medicine at Weill Cornell Medicine, and an attending physician in the Hospital for Special Surgery Division of Rheumatology.
“Since then, belimumab and voclosporin have been approved by the US Food and Drug Administration for treatment, prompting a conceptual shift from induction and maintenance therapy to one of combination, ongoing therapy targeting different parts of the immune system.”
The goal of lupus nephritis treatments is to preserve kidney function and reduce morbidity and mortality of chronic kidney disease while minimizing medication-related toxicities.
Speaking on the college’s ACR on Air podcast, Professor Samaritano revealed a small army of almost 70 people had been working on the guideline since 2023.
“In another departure from the previous ACR lupus nephritis guideline, we really wanted to include all patients with lupus nephritis, whatever their age,” she said.
“So we feel that these recommendations apply to all patients, regardless of age. Understanding, though, that certain groups of patients have specific challenges, especially paediatric patients and also older patients.
“We do have some specific guidance in the manuscript regarding paediatric patients, especially in terms of, you know, maximal dose of glucocorticoids, monitoring growth and puberty development, trying to optimise transition from paediatrics to adult rheumatology.
“And we also have a good practice statement, as we call them, regarding taking a special care with older patients who are prone to the risks of polypharmacy and may have decreased GFRs related simply to age. So we really tried to encompass the whole population of lupus nephritis patients.”
The guideline summary provides 41 recommendations and good practice statements. Key recommendations include:
Screening
- Strong recommendation to screen at least every six to 12 months for protein in the urine (proteinuria) in patients with SLE without known kidney disease, or when experiencing extra-renal flares.
- Conditional recommendation to perform a kidney biopsy in patients with SLE who have high levels of protein in the urine (> 0.5 g/g) and/or impaired kidney function not otherwise explained.
Treatment
- Conditional recommendation for a triple immunosuppressive regimen in patients with active Class III & IV lupus nephritis: Triple therapy for Class III/IV lupus nephritis includes glucocorticoid, and one of three immunosuppressive combination regimens: mycophenolate plus belimumab, mycophenolate plus calcineurin inhibitor therapy, or low dose cyclophosphamide plus belimumab.
- Conditional recommendation for treatment with a specific “triple therapy” as the most desirable therapy for pure Class V lupus nephritis with proteinuria greater than 1 g/g: Triple therapy for Class V lupus nephritis includes glucocorticoid, mycophenolate, and calcineurin inhibitor therapy.
- Conditional recommendation for a lower dose glucocorticoid regimen (after initial intravenous pulse therapy) to minimize toxicity, starting at 0.5 mg/kg/day prednisone (maximum of 40 mg daily) with taper to a prednisone goal of less than or equal to 5 mg/day by six months of treatment.
Monitoring
- Strong recommendations to quantify proteinuria at least every three months in patients with lupus nephritis who have not achieved complete renal response and every three to six months in patients with sustained complete renal response.
Lupus nephritis manifests in close to half of SLE patients and carries a mortality rate of up to 30% at 10 years. It is estimated that 10-22% of patients with the condition will develop end-stage kidney disease.
“We also acknowledge that therapeutic decisions will vary depending on clinical presentation and patient preferences and may be limited by access to specialists, procedures, and medications,” said Professor Sammaritano.
“When recommended medications are unavailable, this guideline should not preclude using available traditional therapies.”
The guideline recommendations were based on systematic evidence reviews, values and preferences from a lupus nephritis patient panel, and input from adult and paediatric rheumatologists and nephrologists, and a rheumatology physician assistant.
The recommendations are intended to promote optimal outcomes for the most commonly encountered lupus nephritis scenarios. The guideline includes therapies available in the US in 2024 and applies to lupus nephritis in adults, children, and adolescents. This is the first time the ACR has included children and adolescents in their lupus treatment guidelines.
The full guideline manuscript will soon be submitted for peer review for inclusion in the ACR’s journals, Arthritis Care & Research and Arthritis & Rheumatology. The ACR expects to publish the manuscript in 2025.
