Belimumab Decreases Flare Rates for Lupus Nephritis

Belimumab (Benlysta) is approved for active lupus despite standard therapy, but there is limited data available on the efficacy of the drug to treat lupus nephritis.

A team, led by Dr. Valentina Binda of Milan, Italy, tested the treatment in 17 female participants with lupus nephritis at a pair of Nephrology Italian Units. Each patient was followed for a median period of 36 months.

The investigators sought varying indications for the patient population, including were arthralgia (n = 3), cutaneous manifestations (2), residual proteinuria (8), and the need to reduce steroids for severe side effects (4).

One patient additionally began therapy during peritoneal dialysis and continued following a kidney transplantation because of non-responsive arthralgias.

Both arthralgia and skin manifestation resolved in all of the patients in the study, while proteinuria normalized in 3 patients and stabilized in all but 1 of the remaining patients. Steroids were indefinitely stopped in 6 patients (35%) and reduced to approximately 40% of the basal dosage in all the other patients.

During belimumab therapy, the investigators diagnosed 3 extrarenal and 1 renal systemic lupus erythematosus cases to account for a rate of renal flares of .02 per patient per year. There were no major adverse events leading to therapy withdrawal.

From a clinical standpoint, arthralgia resolved, immunological parameters, and prednisone could be reduced within a few months in the patient who started belimumab during peritoneal dialysis.

“Belimumab allows the achievement of complete response together with the withdrawal or the reduction of corticosteroids in almost all our patients,” the authors wrote. “Of interest its satisfactory use in a patient in peritoneal dialysis and after kidney transplantation.”

During the American Society of Nephrology (ASN) Kidney Week in Washington, D.C., Brad Rovin, MD, department director of Nephrology at The Ohio State University Wexner Medical Center, explained in an interview with HCPLive® some of the gaps in treatment of lupus nephritis and what is needed in the future to improve patient outcomes.

The results of a phase 2 trial presented at the American College of Rheumatology (ACR) 2019 Annual Meeting in Atlanta, GA, also showcased obinutuzumab, a type 2 anti-CD20 monoclonal antibody, as a promising treatment for proliferative lupus nephritis.

The randomized, double-blind, placebo-controlled NOBILITY trial evaluated the efficacy and safety of obinutuzumab in combination with mycophenolate mofetil in 125 patients and found use increased complete and partial renal responses compared to placebo in the treatment of proliferative lupus nephritis.

Of the 125 patients in the study, 63 were randomized to receive obinutuzumab and 62 were randomized to the placebo arm.

The primary outcome measure of the study was complete renal response at week 52, which investigators defined as achieving UPCR less than .5, normal serum creatinine not increased by more than 15% from baseline, urine red blood cells less than 10 HPF without red blood cell casts.

Secondary endpoint measures for the study included achievement of overall renal response (ORR), modified complete renal response without urinary sediment, and improvements in serologics markers of activity.

At 52 weeks, 34.9% of patients achieved the primary endpoint in the obinutuzumab group compared to 22.6% of the placebo group (12.3% delta; 80% CI, 2.1-22.6%; P = .115). In regard to ORR, investigators noted 55.6% of patients receiving obinutuzumab and 35.5% of patients receiving placebo achieved ORR at week 52 (20.1% delta; 80% CI, 8.9-31.3%; P = .025).

The study, “Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient),” was published online in the Journal of Nephrology.