Jonathan Barratt, MD: Matching-Adjusted Indirect Comparisons of eGFR slopes for IgAN Treatments

A matching-adjusted indirect comparison of eGFR slopes from the PROTECT trial, the NefIgArd trial, and the RaDaR registry is offering new insight into the effects of sparsentatn and irbesartan against standard of care alone and standard of the car plus optimized RASI.

Despite the desires of clinicians across medicine, the field seldom witnesses prospective randomized trials comparing therapies in a head-to-head fashion. With this in mind, investigators designed a matching-adjusted indirect comparison of eGFR slopes among patients receiving sparsentan, irbesartan, or placebo from the PROTECT study, the RaDaR registry, and the NefIgArd trial, respectively.

From PROTECT, investigators obtained information related to 202 patients receiving sparsentan and 202 patients receiving irbesartan. From the NefIgArd trial and the RaDaR registry, investigators identified 717 patients receiving placebo therapy or standard of care for inclusion in the study’s control group.

The primary outcome measured was the annualized 2-year decline in estimated glomerular filtration rate (eGFR), with matching-adjusted 2-year eGFR total slopes for irbesartan and sparsentan cohorts estimated from PROTECT and compared with those from the RaDaR and NefIgArd trials.

Prior to matching, patients in the PROTECT trial were older, had lower SBP, lower eGFR levels, and a longer duration since biopsy compared to the controls within the RaDaR registry. In contrast, the PROTECT trial had older patients with higher blood pressure, a higher proportion of baseline diabetes, longer duration since biopsy, lower eGFR levels, and lower urine protein levels than those in the NefIgArd trial,

After weighting, effect modifiers and prognostic factors were balanced between cohorts. Findings showed a slower decline in kidney function in sparsentan-treated patients as well as irbesartan-treated patients compared to those from RaDaR and those receiving optimized RASI in NefIgArd.

The difference in 2-year eGFR slope was 1.12 ml/min/1.73 m² per year for irbesartan (P = .0239) and 1.89 ml/min/1.73 m² per year for sparsentan (P = .0004) compared to the controls within the RaDaR trial. When compared to those receiving optimized RASI in NefIgArd, results pointed to a difference of 1.30 ml/min/1.73 m² per year with irbesartan (P = .0395) and 2.26 ml/min/1.73 m² per year with sparsentan (P = .004).

Check out our interview with study investigator Jonathan Barratt, MD, of the University of Leicester, for more insight into this study and how it can help inform care of patients with IgA nephropathy.

Relevant disclosures of interest for Barratt included Argenx, Calliditas Therapeutics, Chinook Therapeutics, Galapagos NV, GSK, Novartis, and Travere Therapeutics.

References:

Gong W, Diva U, Bensink, M, et al. Matching-Adjusted Indirect Comparisons of eGFR slopes in the PROTECT study with UK RaDaR IgA Nephropathy population and the control arm of NefIgArd. Abstract presented at 61st European Renal Association Congress. Stockholm, Sweden. May 23-26, 2024.