Antiphospholipid syndrome (APS) is a thrombo-inflammatory disease caused by the persistent presence of antiphospholipid antibodies (aPLs), leading to manifestations such as thrombosis, recurrent pregnancy loss, thrombocytopenia, livedo reticularis, and cardiac valve lesions. It frequently occurs secondary to systemic lupus erythematosus (SLE). Current treatment primarily relies on anticoagulation. This study aims to investigate the effect of telitacicept, a dual-target B-cell inhibitor, on reducing aPLs and modulating B lymphocyte subsets in patients with APS secondary to SLE, providing a theoretical basis for immunotherapy in this condition.

This was a multicenter, prospective, single-arm and self-controlled study. Patients meeting the diagnostic criteria for SLE (2012 SLICC criteria) and APS (2006 revised Sapporo criteria) were enrolled. Telitacicept (160 mg) was administered subcutaneously once weekly for 6 months, in addition to their standard treatment for SLE with secondary APS (including glucocorticoids, hydroxychloroquine, immunosuppressants, anticoagulation and antiplatelet therapy). The primary outcomes were changes in aPLs level, including IgA/IgG/IgM isotypes of anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (anti-β2GP1), lupus anticoagulant (LA), and B lymphocyte subsets, as well as the occurrence of new thrombotic events and adverse reactions. Statistical analysis was performed using the Wilcoxon signed-rank test.

A total of 9 patients completed the follow-up, all female, with a mean age of 39.8±8.6 years. Compared to baseline, levels of aCL-IgG, aCL-IgM, anti-β2GP1-IgG, and anti-β2GP1-IgM were significantly reduced after 3 months of treatment (P<0.05). After 6 months of treatment, these parameters remained significantly decreased, with statistical significance. LA levels showed a decrease but without statistical difference. At 6 months, the total B-cell count, transitional B-cell count, and the percentage and count of naive B cells were significantly decreased compared to baseline (P<0.05). Furthermore, the erythrocyte sedimentation rate (ESR) was significantly reduced at 6 months compared to baseline [19 (16, 28) vs. 10 (6, 19), P=0.042]. During the follow-up period, no patient experienced new thrombotic events or significant adverse drug reactions.

Telitacicept can effectively and safely reduce aPLs levels in patients with APS secondary to SLE. This effect may be mediated by reducing antibody production through modulation of naive and transitional B-cell levels, thereby remodeling B-cell homeostasis. Larger, randomized controlled trials with longer follow-up periods are needed to determine the long-term efficacy of telitacicept in treating SLE with secondary APS.