Abatacept may drive earlier, sustained response in lupus nephritis

The selective T cell costimulation modulator abatacept can lead to a rapid improvement in proteinuria, which induces earlier, sustained complete response compared with placebo in patients with active class III or IV lupus nephritis, although the rate of complete response is similar between groups, suggests a study presented at the EULAR 2018 Congress.

“Novel treatment strategies for active class III or IV lupus nephritis aim to improve renal response rates as well as the speed, robustness, and durability of responses,” according to lead author Dr Richard Furie from the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, US.

In the phase III, double-blind, multicentre trial, 405 patients (mean age 33 years) with active proliferative lupus nephritis were randomized to placebo or intravenous abatacept 30 mg/kg for 3 months, followed by abatacept ~10 mg/kg Q4W on a background therapy of glucocorticoids and mycophenolate. [EULAR 2018, abstract OP0253]

At 1 year, the primary endpoint of a complete response — a composite of glomerular filtration rate maintenance, urine protein-to-creatinine ratio (UPCR) ≤0.5, prednisone ≤10 mg/day, and absence of urinary cellular casts — occurred in 35.1 percent of patients receiving abatacept and 33.5 percent receiving placebo (p=0.73).

Although complete response rate was not significantly different between the two groups, a sustained complete response (in two consecutive visits) was achieved earlier and more frequently in the abatacept arm than the placebo arm — as indicated by a divergence of the Kaplan-Meier plot of the two treatment arms on time to first sustained complete response, in favour of abatacept.

“These benefits were driven by improvement in proteinuria which was seen as early as day 85,” noted Furie. UPCR decreased by 2.50 with abatacept and by 2.00 with placebo, and the change was sustained beyond year 2 (adjusted mean change, -3.13 vs -2.72; difference, -0.41, 95 percent confidence interval [CI], -0.79 to -0.03).     

According to the researchers, improvements in pharmacodynamic markers related to systemic lupus erythematosus such as C3, C4 and anti-dsDNA* autoantibody were also more sustained in patients treated with abatacept.

Renal function, as assessed by eGFR**, was not negatively affected by the active drug.

The safety profile of abatacept was consistent with what was already known, with few nonrenal lupus flares adjudicated as BILAG*** A or B events occurring in year 1 (13 and 12 in the abatacept and placebo arms, respectively).   

Serious adverse events were reported in 24 percent of patients in the abatacept arm and 19 percent in the placebo arm within the first year, and improved to 6 percent and 13 percent, respectively in the second year.

“There was a favourable safety profile extending beyond 2 years of treatment,” observed Furie, who suggested that further analyses and investigations be conducted to explore the potential of abatacept in lupus nephritis.