Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency

LPS-responsive beige-like anchor (LRBA) deficiency (LRBA–/–) and cytotoxic T-lymphocyte–associated antigen-4 (CTLA4) insufficiency (CTLA4+/–) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown. Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up. The 98 patients (63 LRBA–/– and 35 CTLA4+/–) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies. The LRBA–/– patients exhibited a more severe disease course than did the CTLA4+/– patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA–/– patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival. Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation.