Comparative effectiveness of budesonide EC and telitacicept in proteinuria and eGFR trajectories in IgA nephropathy: a retrospective cohort study.

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. However, the lack of direct comparative evidence between the emerging targeted therapies, budesonide enteric-coated (EC) capsule and telitacicept, creates uncertainty in clinical decision-making. This study aimed to conduct a head-to-head comparison of their efficacy in reducing proteinuria and preserving renal function, and to explore efficacy stratification based on baseline characteristics. Methods: We conducted a single-center retrospective cohort study at Henan Provincial People's Hospital, including 95 adults with biopsy-proven IgAN who initiated budesonide EC (n ;= ;46) or telitacicept (n ;= ;49) from January 2022 to December 2025. We assessed 6-month changes in 24-hour proteinuria and eGFR using linear mixed-effects models adjusted for prespecified baseline covariates-age, sex, time from biopsy to treatment, baseline proteinuria and eGFR, comorbidities, and concomitant medications. Findings were evaluated in six sensitivity analyses. Results: In this selected cohort of 95 patients with biopsy-proven IgAN, the effect of treatment on proteinuria reduction was modified by baseline proteinuria level (interaction P = 0.003), with greater relative benefit of telitacicept observed at mild-to-moderate baseline proteinuria. This interaction remained significant in a propensity score-matched (PSM) analysis (p = 0.003). Budesonide EC was associated with a higher mean eGFR during follow-up in the primary model (β = 4.090 mL/min/1.73 m²; p = 0.018), though this association attenuated and lost statistical significance in the matched cohort (β = 5.022 mL/min/1.73 m²; p = 0.085). Conclusions: The relative antiproteinuric effect of telitacicept versus budesonide EC may be modified by baseline proteinuria, with a possible trend toward greater benefit in patients with mild-to-moderate levels. In contrast, although budesonide EC was associated with higher mean eGFR during follow-up in the primary analysis, this difference attenuated after PSM and likely reflects baseline imbalance rather than a true differential effect on renal trajectory. These observations are limited by the retrospective design and residual confounding, and require confirmation in larger prospective studies.