03220nam a2200301   4500001000800000007000300008008004100011040000800052041000800060100003100068245005700099300002300156520228800179650001802467650002502485650003802510650003002548650003102578650002402609700002402633700002902657700002302686700002602709700002502735773011002760942003102870999001702901ESSALUDta      t        pe ||||| |||| 00| 0 spa d  aBMG  aspa  aBarratt, Jonathan  953827  aIptacopan in IgA nephropathy — Final 24-month data  apáginas: 465-477  aBackground: Overactivation of the alternative complement pathway contributes to IgA nephropathy and glomerular inflammation. In the 9-month interim analysis of this phase 3 trial, iptacopan, a complement factor B inhibitor, led to a significant reduction of 38.3% in the 24-hour urinary protein-to-creatinine ratio as compared with placebo and had an acceptable safety profile.
Methods: In this phase 3 trial, we enrolled adults who had IgA nephropathy, an estimated glomerular filtration rate (eGFR) of at least 30 ml per minute per 1.73 m2 of body-surface area, and a 24-hour urinary protein-to-creatinine ratio of 1 or higher (with protein and creatinine both measured in grams) despite supportive care. Patients were randomly assigned, in a 1:1 ratio, to receive oral iptacopan (200 mg) or placebo twice daily. The primary end point for the final analysis was the annualized total eGFR slope as estimated over a 24-month period. Secondary end points included a composite kidney-failure end point (i.e., a sustained decline in eGFR of ≥30%, a sustained eGFR of <15 ml per minute per 1.73 m2, the initiation of maintenance dialysis, receipt of kidney transplant, or death from kidney failure), assessed in a time-to-event analysis. Safety was also assessed.
Results: Among 477 patients included in the final analysis, 238 had been randomly assigned to iptacopan and 239 to placebo. The annualized total eGFR slope was −3.10 ml per minute per 1.73 m2 per year with iptacopan, as compared with −6.12 ml per minute per 1.73 m2 per year with placebo (difference, 3.02 ml per minute per 1.73 m2 per year; 95% confidence interval [CI], 2.02 to 4.01; adjusted P<0.001). A composite kidney-failure end-point event occurred in 21.4% of the patients in the iptacopan group, as compared with 33.5% of those in the placebo group (hazard ratio, 0.57; 95% CI, 0.40 to 0.81; adjusted P=0.003). The incidence of adverse events was 87.0% in the iptacopan group and 89.1% in the placebo group. Serious adverse events occurred in 12.2% of the patients who received iptacopan and in 11.7% of those who received placebo, and serious infections in 6.7% and 2.1%, respectively. No deaths occurred.
Conclusions: Iptacopan therapy led to a significantly slower decline in kidney function than placebo  aALERGIA97055  aINMUNOLOGÍA934121  aENFERMEDAD RENAL CRÓNICA932213  aMEDICINA CLÍNICA933681  aGASTROENTEROLOGÍA912562  aNEFROLOGÍA913133  aEren, Necmi 953828  aKashihara, Naoki 953829  aMaes, Bart 953830  aRizk, Dana V. 953831  aRovin, Brad  9538320 022717922638dMassachusetts NEJM GroupoNEJM005tThe New England Journal of Medicine wESSALUDx0028-4793  cARTICULOSe2026-07-31zSQB  c22753d22753