Iptacopan's effect on kidney decline in IgA nephropathy held through four years

Design

Open-label rollover extension of a phase 3 randomised trial

Population

368 adults with IgA nephropathy from APPLAUSE-IgAN (194 continuing iptacopan, 174 switching from placebo)

Primary outcome

Annualised eGFR slope and proteinuria to 48 months

Effect

eGFR slope −3.49 (−4.17 to −2.80); switchers −5.29 before vs −2.11 after; UPCR ratio 0.61 (0.50–0.75)

Kidney International published the open-label extension of APPLAUSE-IgAN on 22 October. In the randomised phase, iptacopan, an oral factor B inhibitor of the alternative complement pathway, slowed eGFR decline by about 3 mL/min/1.73 m² per year more than placebo over 24 months. In the extension, 194 patients continued iptacopan and 174 switched from placebo, all on supportive care.

In those treated for up to 48 months, eGFR declined by 3.49 per year, and proteinuria stayed about 39% below baseline. Those who switched from placebo had been losing 5.29 per year; after switching, the slope improved to 2.11 per year, and proteinuria fell. Safety over up to five years was consistent with what was known, with no new signals.

The switch data are the most informative part: the same patients declined more slowly once treated. Still, this is an uncontrolled extension, and patients who continue in extensions tend to be those doing well.

Iptacopan requires vaccination against encapsulated bacteria because it inhibits complement. Its availability and cost in India should be checked before discussion with patients.

• Consider complement inhibition for IgA nephropathy with persistent proteinuria despite optimised supportive care, where available.
• Keep RAS blockade and SGLT2 inhibition as the foundation of treatment.
• Ensure vaccination against encapsulated organisms before starting a complement inhibitor.
• Track eGFR slope and proteinuria to judge response over time.

Why it matters

It adds durability data for a targeted therapy in the commonest primary glomerulonephritis.

Don't overread it

The extension was open-label and uncontrolled; the slopes are not a randomised comparison.

The statistics, in plain English

An eGFR slope of −3.49 (95% CI −4.17 to −2.80) means kidney function fell by about 3.5 units a year on treatment. In switchers, the slope moved from −5.29 to −2.11, roughly halving the rate of loss. A proteinuria ratio of 0.61 means levels about 39% below where they started.

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