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ABACHAI phase 2 clinical trial: Safety and efficacy of subcutaneous abatacept in patients with CTLA-4 insufficiency or LRBA deficiency

Year: 2026

Type: article

Abstract: BACKGROUND: Heterozygous germline mutations in CTLA4 (CTLA-4 insufficiency) and biallelic mutations in LRBA (lipopolysaccharide-responsive beige-like anchor protein [LRBA] deficiency) cause immune dysregulation with autoimmunity, lymphoproliferation, and immunodeficiency. For treatment, abatacept has been used successfully and is increasingly being used off-label; however, prospective clinical trial data are missing. OBJECTIVE: We evaluated the safety and efficacy of abatacept in patients with CTLA-4 insufficiency or LRBA deficiency. METHODS: ABACHAI was a prospective, open-label, single-arm phase 2a trial. Adult patients with genetically confirmed CTLA-4 insufficiency or LRBA deficiency and at least one clinically significant organ manifestation received 125 mg abatacept subcutaneously once a week for 12 months. The primary end point was safety, defined as the number of episodes of failed infection control. Secondary end points included additional safety parameters, efficacy outcomes, and patient-reported quality of life. RESULTS: Twenty patients were enrolled (18 with CTLA-4 insufficiency and 2 with LRBA deficiency). Three patients had 5 severe infections during treatment (incidence rate, 0.27 per patient-year), comparable to the year before enrollment. No Epstein-Barr virus or cytomegalovirus reactivations occurred. Abatacept reduced lymphoproliferation and immune activation and improved patient-reported quality of life and gastrointestinal symptom quality. Cytopenias and renal involvement were not sufficiently controlled. Four patients (20%) discontinued therapy, 3 because of unrelated serious adverse events and 1 because of noncompliance. CONCLUSION: ABACHAI was the first prospective interventional trial examining abatacept treatment in CTLA-4 insufficiency and LRBA deficiency. Abatacept demonstrated a favorable safety profile and organ-specific efficacy, with strongest responses in lymphoproliferation and immune activation. Patients with refractory cytopenias or progressive organ involvement may require additional or alternative therapeutic strategies.

Source: Journal of Allergy and Clinical Immunology

DOI: 10.1016/j.jaci.2026.09.007