Long-term efficacy and safety for the complement factor B inhibitor iptacopan in IgA nephropathy
Kidney International, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.kint.2026.09.017
- Dergi Adı: Kidney International
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
- Anahtar Kelimeler: clinical study, complement, estimated glomerular filtration rate, IgA nephropathy, proteinuria
- İstanbul Üniversitesi-Cerrahpaşa Adresli: Hayır
Özet
Introduction: Iptacopan, a factor B inhibitor, targets alternative complement pathway overactivation, a key driver of glomerular inflammation in IgA nephropathy. In the phase 3 APPLAUSE-IgAN trial (NCT04578834), iptacopan significantly slowed kidney function decline versus placebo over 24 months (difference in total estimated glomerular filtration rate [eGFR] slope: 3.02 ml/min per 1.73 m2 per year [95% confidence interval (CI) 2.02, 4.01; P < 0.001]). Methods: Patients who completed APPLAUSE-IgAN or the phase 2 iptacopan trial (NCT03373461) could enter an open-label rollover extension program (REP) (NCT04557462). Patients in this REP receive oral iptacopan 200 mg twice daily alongside supportive care. Patients from the phase 2 trial were not included in efficacy analyses. Results: Overall, 194 and 174 patients from the APPLAUSE-IgAN iptacopan and placebo arms, respectively, entered the REP. In patients who received iptacopan for up to 48 months, the total annualized eGFR slope was −3.49 ml/min per 1.73 m2 per year (95% CI −4.17, −2.80). Urine protein-to-creatinine ratio from first morning void (UPCR-FMV) reduction was sustained through 48 months with iptacopan (geometric mean ratio to baseline: 0.61 [95% CI 0.50, 0.75]). Before receiving iptacopan, the total eGFR slope over 24 months in APPLAUSE-IgAN placebo arm patients who entered the REP was −5.29 ml/min per 1.73 m2 per year (95% CI −6.09, −4.49). After switching to iptacopan, the total eGFR slope improved to −2.11 ml/min per 1.73 m2 per year (95% CI −3.08, −1.13) over the next 24 months. UPCR-FMV decreased after switching (geometric mean ratio to baseline at month 48: 0.74 [95% CI 0.59, 0.91]). Long-term safety up to 5 years (median treatment duration: 29.9 months) was consistent with the known profile of iptacopan. Conclusions: Long-term treatment with iptacopan led to sustained slowing in eGFR decline and proteinuria reduction that were also observed after switching from placebo. No new safety signals were observed. Trial Registration: Registered at ClinicalTrials.gov with study numbers NCT04578834 (APPLAUSE-IgAN), NCT03373461 (phase 2 trial of iptacopan in IgAN), and NCT04557462 (rollover extension program).