Abstract
BACKGROUND: This study aimed to evaluate the efficacy and safety of telitacicept versus mycophenolate mofetil (MMF) in high-risk progressive immunoglobulin A nephropathy (IgAN). METHODS: This retrospective, multicentre cohort study included patients with high-risk progressive IgAN who received telitacicept or MMF therapy, both combined with low-dose steroids. Clinical data were collected from treatment initiation to 12 months. RESULTS: A total of 104 patients were included, with 56 receiving MMF and 48 receiving telitacicept. The average age was 36.9 ± 11.8 years. Baseline characteristics were well balanced between groups, except for serum albumin, uric acid and tubular pathology based on the Oxford classification, which showed significant differences. At 12 months, telitacicept plus low-dose steroids demonstrated superior proteinuria reduction (-62.5% versus -52.9%, P = .041) and stabilized renal function (4.1% improvement in estimated glomerular filtration rate versus 5.3% decline with MMF, P = .085). Telitacicept plus low-dose steroids achieved higher complete remission rates (33.3% versus 16.1%; P = .04) and significantly lower non-response rates (29.2% versus 48.2%, P = .048) compared with MMF plus low-dose steroids. Cumulative remission rates (complete + partial) favoured telitacicept at all time points, with the largest difference at 12 months. Notably, telitacicept required substantially lower cumulative glucocorticoid doses (P < .001) and exhibited a superior safety profile, with significantly fewer adverse events (22.9% versus 42.9%, P = .032) and no serious complications reported. Multivariable analysis indicated telitacicept was associated with a higher likelihood of achieving 12-month complete remission [adjusted hazard ratio 6 (95% confidence interval 1.41-25.62). CONCLUSIONS: Telitacicept may offer better efficacy compared with MMF for proteinuria reduction in high-risk IgAN patients, while reducing combined glucocorticoid requirements and demonstrating a more favourable safety profile. These advantages position it as a promising therapeutic option, warranting further randomized validation.