Safety and efficacy of subcutaneous abatacept (125 mg once weekly for 12 months) in adults with genetically confirmed CTLA-4 insufficiency or LRBA deficiency with at least one clinically significant organ manifestation, in a prospective open-label single-arm phase IIa trial.
Among 20 enrolled patients, the severe infection incidence rate was 0.27 per patient-year (5 episodes in 3 patients) — comparable to the pre-enrolment year — with no EBV or CMV reactivations. Abatacept reduced lymphoproliferation and immune activation and improved quality of life and GI symptom scores, but cytopenias and renal involvement were not sufficiently controlled; 4 patients (20%) discontinued.
Very small sample (n=20) with only 2 LRBA deficiency patients, limiting conclusions for that subgroup. Single-arm design with no control group makes it impossible to separate treatment effects from natural disease course. Study was limited to adults, so findings may not apply to children.
Subcutaneous abatacept appears safe and effective for lymphoproliferation and immune activation in CTLA-4 insufficiency, and can be considered as a structured therapy in these patients. Those with refractory cytopenias or progressive renal involvement likely need additional or alternative treatments beyond abatacept alone.
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