Dual BAFF/APRIL inhibition with telitacicept in systemic lupus erythematosus and IgA nephropathy: pharmacological rationale, clinical efficacy, and safety on female fertility preservation

Background Systemic lupus erythematosus (SLE) and IgA nephropathy (IgAN) are immune-mediated renal disorders characterized by aberrant B-cell activation. While SLE shows a striking female predominance, IgAN is more prevalent in males; nonetheless, both conditions typically peak the during reproductive years. Their pathogenesis involves distinct molecular drivers: SLE is mediated by specific autoantibodies, whereas IgAN is initiated by galactose-deficient IgA1 (Gd-IgA1) acting as a primary antigen that elicits immune complex deposition. Conventional immunosuppressive therapies are effective but limited by non-selective toxicity, particularly in women of reproductive age. Telitacicept, a first-in-class recombinant transmembrane activator and CAML interactor (TACI)–fragment crystallizable (Fc) fusion protein, simultaneously neutralizes B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), offering a targeted pharmacological strategy. Methods This narrative review synthesizes evidence from randomized controlled trials, real-world studies, and mechanistic investigations to evaluate the pharmacological rationale, clinical efficacy, and safety profile of telitacicept in SLE and IgAN, with particular attention to its steroid-sparing effects and endocrine safety. Results Dual inhibition of BAFF and APRIL by telitacicept suppresses pathological B-cell maturation and plasma cell survival, leading to marked reductions in antigen Gd-IgA1 and associated immune complexes, proteinuria, and disease activity, alongside stabilization of renal function. Clinical trials and real-world data demonstrate robust efficacy in both refractory IgAN and active SLE/lupus nephritis, with sustained complement recovery and favorable tolerability. Importantly, available clinical data indicate no direct gonadotoxic effects, with preserved ovarian reserve markers and hypothalamic–pituitary–gonadal axis function, distinguishing telitacicept from cytotoxic immunosuppressants. Conclusion Telitacicept represents a pharmacologically rational, targeted immunomodulator that combines effective disease control with a favorable safety profile. Its dual BAFF/APRIL inhibition and steroid-sparing properties support its potential role as a long-term therapeutic option for patients with SLE and IgAN, particularly women requiring sustained disease control who seek to minimize systemic toxicity and safeguard ovarian reserve.