Neuropsychiatric systemic lupus erythematosus (NPSLE), a severe and heterogeneous manifestation of systemic lupus erythematosus (SLE), poses substantial challenges in clinical management due to its diverse clinical presentations and high associated mortality rates. Although rituximab (RTX), a monoclonal antibody targeting CD20, has been widely used in NPSLE treatment through effective B cell depletion, the therapeutic efficacy and safety of telitacicept, a novel B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) dual inhibitor, in NPSLE remain insufficiently clarified. Therefore, this retrospective study aimed to evaluate the clinical outcomes of telitacicept, either as monotherapy or in sequential use after RTX treatment, in patients with NPSLE.

We retrospectively analyzed clinical data of 38 NPSLE patients recruited from two tertiary medical centers in China between a specified study period. These patients were divided into three groups based on their treatment regimens: the conventional therapy group (n=11, receiving standard immunosuppressants and glucocorticoids), the telitacicept monotherapy group (n=15), and the RTX followed by telitacicept sequential therapy group (n=12). The primary and secondary outcomes included event-free survival (EFS), self-care ability assessment, modified Rankin Scale (mRS) scores for neurological function, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and SLEDAI-neuropsychiatric (SLEDAI-NP) scores.

Compared with the conventional therapy group, both the telitacicept monotherapy group and the RTX plus telitacicept sequential group exhibited effective B cell depletion, significantly improved EFS rates, enhanced self-care ability, and reduced mRS scores, indicating better neurological function recovery. Notably, the RTX followed by telitacicept group achieved the most rapid tapering of glucocorticoid dosage, a key factor in reducing long-term steroid-related adverse effects. In terms of safety, infections in the telitacicept-based treatment groups were mild to moderate and manageable with appropriate interventions, whereas the conventional therapy group had a higher incidence of severe adverse events.

Telitacicept shows promising therapeutic potential in the treatment of NPSLE, both when used as monotherapy and in sequential combination with RTX induction therapy. Although this retrospective study confirms the preliminary efficacy and safety of telitacicept in NPSLE, further large-scale, prospective, controlled clinical trials are required to validate these findings and establish optimal treatment protocols.