Shifting Landscape, Role of Belimumab in SLE and Lupus Nephritis Explored

Treating patients who have systemic lupus erythematosus (SLE) can be challenging, given the heterogeneity of the disease, but a new review article notes that several treatments and treatment combinations are available for SLE and one of its most serious complications: lupus nephritis.

This new report was published in Human Vaccines & Immunotherapeutics.

The authors said lupus nephritis is associated with significant morbidity and mortality in patients with SLE. Standard treatment options include the antimalarial hydroxychloroquine and glucocorticosteroids, among others. For patients whose disease is refractory to treatment, biologics are recommended. Those include belimumab (Benlysta) and, in some cases, rituximab (Rituxan). However, newer therapies could be available soon, the authors noted.

One potential emerging therapy is anifrolumab (Saphnelo), a human monoclonal antibody that blocks the receptor for type 1 interferons and downstream pathogenic signaling pathways.

“The effects seem to be more pronounced in individuals with an increased interferon gene signature, which may be helpful as a biomarker of responsiveness,” the authors wrote.

The calcineurin inhibitor voclosporin (Lupkynis) is approved in the United States, but not yet in Europe, to treat adults with active lupus nephritis. The investigators said it has been linked with improved rates of complete renal response when used with mycophenolate mofetil (MMF; CellCept) and glucocorticosteroids.

Other studies are also underway that could expand the treatment options, the authors added.

For belimumab specifically, the investigators said the therapy would typically be used in cases where patients have active disease or failed to achieve remission despite therapy with glucocorticosteroids, antimalarials, and another immunosuppressive agents. They said belimumab has “excellent efficacy” in patients who have intolerable adverse effects from conventional antimalarials.

However, they added that it is important to consider patient history when using belimumab in patients with lupus nephritis, as this will affect dosing. The investigators said their approach in patients with lupus nephritis is to start remission induction therapy with methylprednisolone for 3 days (with doses between 250 and 1000 mg/d), and then taper in combination with MMF.

“The response is monitored every month for the first 3 months, then every 3 months for the first year,” they wrote.

If that approach fails to achieve at least a partial renal response, they add belimumab to MMF, since they said it is easy to use and does not have the toxicity concerns of cyclophosphamide. They noted, however, that other clinicians may have different approaches and that other combination therapies may be feasible in the future.

“Currently, most evidence exists for [belimumab/rituximab] combinations, but this constitutes an off-label use and should be reserved for refractory cases until more trials become available,” they wrote.

Turning their attention to commercial and access considerations, the authors said that while belimumab is the only biologic approved for SLE and lupus nephritis, many clinicians also use rituximab off label. However, they added, such cases can run into payment issues, since insurers prefer to pay for belimumab, the approved therapy. They added, however, that it is not yet entirely clear whether belimumab works equally well in all demographic groups and that other potential approvals could provide a broader range of choices for therapy.

The investigators concluded that the coming years will likely be full of change and excitement in SLE.

“It is expected that additional combination therapies will be tested and may allow for a considerable reduction of overall [glucocorticosteroid] doses and their well-known side effects,” they wrote. “However, drug development is expensive, and new drugs will be costly for several years.”

Reference

Plüß M, Piantoni S, Tampe B, Kim AHJ, Korsten P. Belimumab for systemic lupus erythematosus - focus on lupus nephritis. Hum Vaccin Immunother. Published online May 19, 2022. doi:10.1080/21645515.2022.2072143