Updated guidance for the management of systemic lupus erythematosus (SLE) reflects the rapid development of new therapies in recent years, notably the approval of the biologic anifrolumab, according to new recommendations issued by the European Alliance of Associations for Rheumatology (EULAR).
“In the case of systemic lupus, several new drugs have been recently approved, and therefore guidance to clinicians is needed,” Richard Furie, MD, told MedCentral. Dr. Furie served as a member of the EULAR Task Force for creating the guidelines and is chief of the division of rheumatology at Northwell Health in Great Neck, NY.
“New therapies approved since the previous recommendations, such as belimumab, voclosporin, and anifrolumab, are discussed in the new recommendations, and older therapies are mentioned as well,” he noted. “For example, the value of hydroxychloroquine in the management of patients with SLE is emphasized. Steroids have been the foundation of medical care for decades, but in the new recommendations, it is suggested that 5 mg of prednisone daily (or less) be the target dose,” he noted. (More on prescribing recommendations below.)
The EULAR international task force reviewed literature from January 2018 to December 2022 to develop the updated recommendations, which included the use of hydroxychloroquine (HCQ), glucocorticoids (GCs), immunosuppressive drugs (ISDs), calcineurin inhibitors (CNIs), and biologics. The guidelines were published online in the Annals of the Rheumatic Diseases.
Guidelines Identify Five SLE Management Principles
The task force identified five overarching principles to guide the management of SLE, starting with the consideration of SLE as a multidisciplinary condition that requires an individualized approach with shared decision-making between clinicians and patients.
The core principles include:
an assessment of SLE disease activity at each clinic visit, with evaluation of organ damage at least once a year
consideration of the role of nonpharmacological interventions
the use of pharmacological interventions based on a variety of factors including patient characteristics, patient preferences, the nature of organ involvement, treatment-related adverse events, comorbidities, and the risk for progressive organ damage
The final principle emphasizes the importance of early SLE diagnosis. Early diagnosis and intervention should include screening for organ involvement, initiating prompt treatment, and monitoring for strict treatment adherence – all with the goal of preventing organ damage and flares, as well as improving prognosis and quality of life.
SLE Medication Maintenance and Intervention Timing
Two important changes in the new recommendations involve maintenance prednisone and the potential for earlier introduction of immunosuppressives, Michelle Petri, MD, MPH, a member of the task force, told MedCentral.
In the current recommendations, “the goal for maintenance prednisone, if it is absolutely necessary, is 5 mg or less,” Dr. Petri said. “The guidelines also make it crystal clear that achieving this goal often means earlier introduction of immunosuppressives and biologic agents.”
Other Prescribing Recommendations and Considerations for SLE
Notably, HCQ is recommended for all individuals with SLE at a target dose of 5 mg/kg of real body weight/day, with consideration of the patient’s risk for flares and retinal toxicity.
The task force also recommends minimizing the use of glucocorticoids to 5 mg/day or less of prednisone equivalent, and that GCs should be withdrawn if possible. Explained Dr. Furie, “Clinicians and patients need to constantly think about the hazards of steroids and therefore keep tapering the dose as manifestations allow.”
The EULAR recommendations further note that the addition of ISDs, such as methotrexate, azathioprine, or mycophenolate, and/or biological agents, such as anifrolumab or belimumab, should be considered for disease control and GC reduction in patients who do not respond to HCQ or who are unable to reduce GC to the recommended level.
For individuals with organ-threatening disease and refractory disease, clinicians should consider cyclophosphamide (CYC) and rituximab, respectively, according to the task force.
The task force also acknowledged the impact of new drugs on the market for lupus nephritis (LN). Their consensus for individuals with active LN calls for GC and mycophenolate or low-dose intravenous CYC initially, with the addition of belimumab or CNIs if needed. Specifically, noted Dr. Furie, “With the approval of several new therapies in recent years, including belimumab and voclosporin for lupus nephritis and anifrolumab for systemic lupus, it is important for the lupus community to become familiar with the use of these drugs,” he said.
Other recommendations addressed in the guidelines include cutaneous, neuropsychiatric, and hematological disease, SLE-associated antiphospholipid syndrome, and kidney protection. Treatment strategies and therapeutic targets, including combination and sequential therapies, how to assess patient response, taper, and prevent infections, are also described.
Hydroxychloroquine and Glucocorticoids Changes in Practice
“The EULAR recommendations are timely amidst newly approved agents in lupus nephritis (LN), and newly published ACR SLE quality measures and guideline projects that are underway,” said Christie M. Bartels, MD, chief of the division of rheumatology at the University of Wisconsin, Madison. “I was excited to see that the EULAR recommendations resonate with our ACR-endorsed lupus quality measures published in Arthritis Care & Research 2023,” she noted.
Dr. Bartels, who was not part of the EULAR task force, also highlighted the importance of changes related to HCQ and GCs compared to previous EULAR recommendations. Specifically, she pointed to “EULAR’s call for HCQ dosing at 5mg/kg, and second, glucocorticoid reduction to prednisone equivalent of 5 mg/day or below vs 7.5 mg prior… Experts agree that prolonged steroids should be minimized, and aiming for a prednisone threshold of 5 mg vs 7.5 mg has evidence for harm reduction,” she explained. “The 5 mg/kg HCQ threshold aligns with ophthalmology recommendations, though several recent studies show higher flare risk at that level. Emerging data and use of HCQ level testing could tailor dosing to maximize benefit over risk.”
As for the takeaway message for practicing clinicians, Dr. Bartels emphasized “the existence of strong evidence to maximize use of HCQ in all eligible patients with lupus, and to minimize prolonged prednisone use.” Moreover, she noted, “it is important to regularly revisit evidence-based care in lupus and LN amid new therapeutic options.”
Looking ahead, areas that need more research are comparative effectiveness and tailored recommendations for SLE and LN treatments, and implementation science on how to deliver evidence-based lupus care, according to Dr. Bartels. “The latter could help us implement guideline-concordant care. This also includes more disparities research on how to overcome barriers like adverse social determinants using multidisciplinary care innovation and data-informed policy,” she said.
Added Dr. Furie, “Although progress has been made in the area of drug development, we still need to increase response rates and reduce toxicity of current interventions in order to improve long-term outcomes.”
Disclosures: Dr. Bartels reported no financial conflicts. Dr. Furie’s and other Task Force members’ disclosures are reported in the EULAR guidelines publication.
