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AMSTERDAM – Abatacept used on top of the standard of care did not improve the primary endpoint of a complete renal response versus placebo in the ALLURE phase 3 study.
Criteria for a complete renal response (CRR) at 1 year was met by 35.1% of abatacept-treated and 33.5% of placebo-treated patients (P = .73). CRR criteria included having a urine protein to creatinine ratio (UPCR) of less than 0.5, a normal estimated glomerular filtration rate (eGFR) or an eGFR of 85% or more of baseline values, no cellular casts, and a daily corticosteroid dose of 10 mg or less.
Sara Freeman/MDedge News
Dr. Richard A. Furie
“We also saw a more rapid decline in proteinuria in those people treated with abatacept, and that seemed to be sustained over the course of the study,” said Dr. Furie, professor of medicine at Hofstra University, Hempstead, N.Y., chief of the division of rheumatology at Northwell Health in Great Neck, N.Y., and a professor at the Center for Autoimmune, Musculoskeletal, and Hematopoietic Diseases in the Feinstein Institute for Medical Research in Manhasset, N.Y. After about 12 weeks, the adjusted mean change in UPCR from baseline was –2.5 for abatacept and –2.0 for placebo; the values at 1 year were a respective –2.95 vs. –2.68 and at 2 years were –3.13 vs. –2.72.
Renal function was not negatively impacted by treatment with abatacept, with about a 5%-8% increase in eGFR seen in both groups.
Furthermore, improvements in lupus-related biomarkers were more pronounced in patients treated with abatacept than placebo, Dr. Furie said. This included a greater decrease in anti–double-stranded DNA autoantibody titers and an increase in complement C3 and C4 levels.
Eric Morand, MD, who was not involved in the ALLURE study, commented during discussion that the main result of the study was “very sad.”
Dr. Morand of Monash University in Melbourne observed that the duration of renal disease at study entry was about 14 months and that around 38% had been previously treated with mycophenolate mofetil (MMF). So, could this have influenced the findings?
Dr. Furie was unable to answer the question but confirmed that MMF was one of two background medications given in the trial, at an oral dose of 1.5 g/day, alongside of oral prednisone up to 60-mg daily.
ALLURE was a 2-year randomized, double-blind study with an open-ended, blinded, long-term extension in 405 patients with active class III or IV lupus nephritis. The aim of the trial was to determine the efficacy and safety of abatacept versus placebo in the treatment of active proliferative lupus nephritis.
Abatacept was given intravenously, first at a dose of 30 mg/kg on days 1, 15, 29, and 57, and then at a dose of 10 mg/kg every 4 weeks.
In terms of safety, 14 deaths occurred during the course of the study and its long-term extension. Seven abatacept patients died in year 1, two of whom died more than 56 days after discontinuing the study drug. Five patients in the placebo group died in year 1, one in year 2, and one in the long-term extension. Rates of any or serious adverse events were similar among the groups, decreasing over time.
“The safety signals were really no different to what we already know about abatacept,” Dr. Furie said. As for the future, more analyses from the trial can be expected, he added.
The study was sponsored by Bristol-Myers Squibb. Dr. Furie disclosed receiving grant or research support from, and acting as a consultant to, the company. All but 3 of the study’s 12 authors had financial ties to many pharmaceutical companies, some of which included Bristol-Myers Squibb. Two authors are employees of Bristol-Myers Squibb. Dr. Monash was not involved in the ALLURE study but has received research support from Bristol-Myers Squibb, among other pharmaceutical companies.
