Antiphospholipid syndrome (APS) is a common complication of systemic lupus erythematosus (SLE). It is a thrombo-inflammatory disease characterized by persistent antiphospholipid antibodies (aPLs), which leading to thrombosis, recurrent pregnancy loss, thrombocytopenia, livedo reticularis, and valvular heart disease. Current treatment mainly relies on anticoagulation. Whether Telitacicept, a dual-target B-cell inhibitor, can effectively reduce aPLs and its mechanism of action in this context remain understudied. This study aims to investigate whether telitacicept can reduce aPLs levels and its effect on lymphocyte subsets in patients with APS secondary to SLE, providing a theoretical basis for its use in this population.

This multicenter, prospective, single-arm, self-controlled study enrolled patients receiving standard treatment for SLE and APS, with the addition of subcutaneous telitacicept 160 mg once weekly, followed for 6 months. Standard SLE treatment included glucocorticoids, hydroxychloroquine, with or without immunosuppressants. Standard APS treatment included anticoagulation and antiplatelet therapy. Patients had received conventional treatment for at least 1 month within the 6 months prior to enrollment. Primary outcome measures included the following aPLs: aCL (IgA, IgG, IgM), anti-β2GPI (IgA, IgG, IgM), and LA; B lymphocyte subsets; as well as new thrombotic events and adverse reactions occurring during the follow-up period. For outcome data analysis, paired t-tests were used for normally distributed data, and Wilcoxon signed-rank tests were used for non-normally distributed data. A P-value <0.05 was considered statistically significant. 

A total of 11 APS patients were enrolled; one patient did not complete the study, and one was lost to follow-up. All patients were female, with a mean enrollment age of 39.8 ± 8.6 years (range 29-55 years). At 6 months of treatment, aCL-IgA was lower than baseline but higher than at 3 months (non-significant); anti-β2GPI-IgA and LA were reduced (non-significant); aCL-IgG, aCL-IgM, anti-β2GPI-IgG, and anti-β2GPI-IgM showed significant reductions. Percentages and counts of total B lymphocytes, transitional B lymphocytes, and naive B lymphocytes decreased at the 6-month follow-up. Significant reductions were found in total B lymphocyte count, transitional B lymphocyte count, naive B lymphocyte percentage (of total B cells), and naive B lymphocyte count. Erythrocyte sedimentation rate (ESR) improved significantly at 6 months. No new thrombotic events or adverse drug reactions occurred during follow-up.

This study demonstrates that telitacicept effectively reduces aPLs levels with a favorable safety profile in patients with APS secondary to SLE. This effect may be mediated through reducing antibody production by impacting the levels of naive and transitional B lymphocytes, thereby contributing to the restoration of B-cell homeostasis. Larger, randomized controlled trials with longer follow-up periods are warranted to establish the long-term efficacy of telitacicept in treating SLE complicated by APS.