SLE Recommendations Continue to Evolve as Science Advances

A new review article outlines current agreements and disagreements between association guidelines, but notes the recommendations are likely to change more in the future.

Treatment of systemic lupus erythematosus (SLE) has evolved significantly in recent years, with the emergence of high-quality evidence and multiple sets of patient-management recommendations. Yet, those recommendations differ in some key aspects, including in how they deal with questions when only low-level evidence is available.

In a new review article in Rheumatic Disease Clinics, George Bertsias, MD, PhD, of the University of Crete Medical School, in Greece, synthesizes the latest research and its implications for clinical practice. He began by explaining some of the reasons obtaining consensus in SLE treatment has been difficult. First, the disease itself can manifest in many ways and affect multiple organs. Also, little evidence has historically been available to guide therapeutic choices, thus leading to wide variance in treatment practices.

“To further complicate matters, multiple medical disciplines (eg, general practitioners, nephrologists, hematologists) can be involved in the diagnosis and treatment of SLE, with often different preferences and practices regarding the selection of immunosuppressive agent, dosage of glucocorticoids, monitoring of treatment response, and assessment of disease outcomes,” Bertsias said.

The American College of Rheumatology published its first set of SLE treatment guidelines in 1999, followed by the European Alliance of Associations of Rheumatology in 2008. Other sets of recommendations have followed. Bertsias said an examination of those recommendations produces key differences.

One pertains to hydroxychloroquine dosing and specifically whether dosage should be limited to no more than 5 or 6.5 mg/kg per day. Similar disagreements surround the starting dose for glucocorticoids to manage active cases and flares. Not only is the dosage the subject of disagreement, but guidelines also differ on how to arrive at the dosage. The Asia-Pacific League for Associations of Rheumatology guidelines suggest the drug be used only for active renal and neuropsychiatric disease, whereas the British Society of Rheumatology guidelines base their dosing and administration on the degree of activity and severity.

Belimumab (Benlysta) is commonly recommended for many patients whose disease is active despite conventional therapy. Yet, Bertsias said, “the community is still struggling to define the subgroups of patients who may benefit the most from belimumab and thus maximize its cost-effectiveness.”

Bertsias next discussed the management of patients with lupus nephritis, noting both points of agreement and areas of disagreement, including with regard to which patients should get cyclophosphamide and the dosing of glucocorticoids.

He summarized the recommendations, however, by stating that active lupus nephritis should be initially treated either by mycophenolate or low-dose intravenous cyclophosphamide, with or without glucocorticoids.

“High-dose cyclophosphamide should be reserved for aggressive disease,” he added.

Bertsias closed by summarizing key points for clinicians. Among them, he said treatment ought to be based on severity and activity based on valid clinical instruments, and patients should be monitored throughout treatment for drug-related adverse events and comorbidities.

He said biologics are suitable for patients with persistent disease activity or frequent flares despite conventional therapy.

Looking forward, Bertsias said it is likely that recommendations for SLE treatment will continue to evolve as new therapies are approved. As that happens, he said it will be important for future expert panels to “build on the previously appraised evidence and gained experience to focus on areas of uncertainty with low evidence base and try to upgrade them, improve clarity where needed, and identify emergent topics of relevance to the disease, physicians, and patients.”


Bertsias G. Recommendations for systemic lupus erythematosus: balancing evidence and eminence to facilitate the medical care of a complex disease. Rheum Dis Clin N Am. doi:10.1016/j.rdc.2022.05.001

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