medwireNews: The addition of abatacept to standard therapy does not increase the rate of complete renal response among patients with lupus nephritis, phase III study findings show.
The study did show, however, that these patients achieved an earlier and more sustained complete response with the selective T-cell co-stimulation modulator, which was largely driven by a more rapid improvement in proteinuria levels.
A complete response was defined as the composite of a normal estimated glomerular filtration rate (eGFR) or no worse than 85% of baseline, a urine protein-to-creatinine ratio (UPCR) of below 0.5, absence of urinary casts, and a prednisone dose of 10 mg/day or below.
A total of 405 patients with active class III or IV lupus nephritis and a UPCR of 1 or above participated in the trial. Of the 202 patients who were randomly assigned to receive intravenous abatacept 30 mg/kg for 3 months followed by 10 mg/kg every 4 weeks in addition to mycophenolate and glucocorticoids, 35.1% achieved a complete response after 52 weeks of treatment.
This was not significantly different to the 33.5% rate among the 203 patients who received placebo in addition to standard therapy.
The driver for complete response was proteinuria, with about 40% of patients in either group achieving the criteria for that endpoint, said Richard Furie (Northwell Health, New York, USA), presenting the findings at the 2018 EULAR meeting in Amsterdam, the Netherlands.
“But the provocative finding is […] the time to first sustained complete renal response,” he highlighted. “You see an earlier and also a more robust response in the abatacept group.”
In all, 48% of patients in this group achieved a sustained complete response, defined as remaining in complete response for at least two consecutive visits approximately 4 weeks apart, at day 365, compared with 38% of patients in the placebo group.
“We also saw a more rapid decline in proteinuria in those treated with abatacept and that seemed to be sustained over the course of the study,” Furie noted.
A difference between the two groups was seen as early as day 85, at which point the UPCR had dropped an average of 2.50 versus 2.00 points among abatacept- and placebo-treated patients, respectively, from baseline values of 6.43 and 6.50. At day 365, the average UPCR was 1.33 in patients receiving abatacept and 1.53 in those receiving placebo.
There was about a 5–8% increase in eGFR in the two groups, but no significant difference in the number of patients achieving markedly lower eGFR.
Abatacept had a “profound” effect on serologies, Furie reported, including a greater reduction in anti-double stranded DNA antibodies and a greater increase in C3 and C4 complement levels.
Discussing the drug’s safety profile, Furie said that the 14 deaths were evenly split between the two treatment groups and while severe adverse event rates were slightly higher in the abatacept-treatment group in year one (24.3% vs 19.2% with placebo), this pattern reversed by year 2.
The serious infections rates at 1 year were 14.4% and 9.9% for patients taking abatacept and placebo, respectively, while those for severe herpes zoster infection were a corresponding 2.5% and 2.0%. But there were very few opportunistic infections observed in year 1.
“So this study failed to meet its primary endpoint of complete renal response at year 1,” acknowledged Furie, but he added that “there were some provocative findings that need additional analyses and the safety signals were really no different than what we knew about abatacept.”
By Lucy Piper
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