Sustained IFN Signature Suppression with Anifrolumab in a SAVI patient Refractory to JAK Inhibitor and Dazukibart Therapy.

To report the efficacy and safety of interferon-β (IFNβ) neutralizing monoclonal antibody (dazukibart), followed by treatment with anti-IFNAR1 antibody (anifrolumab), in a patient with STING-associated vasculopathy with onset in infancy (SAVI) who had vasculitic ulcers and systemic inflammation refractory to Janus kinase inhibition (JAKi). A SAVI patient with a de novo STING1 p.(Asn154Ser) mutation, a known pathogenic variant, and uncontrolled disease received twenty-one doses of dazukibart under a compassionate use investigational new drug (IND) protocol, followed by treatment with the anti-IFNAR1 antibody anifrolumab. Clinical and laboratory parameters, including wound healing, whole-blood type I interferon (IFN I) signature, and safety markers were closely monitored throughout both treatment periods. Despite initial reductions in C-reactive protein (CRP) levels and IFN I scores following dazukibart administration, the patient experienced rebound inflammation and recurrent vasculitic lesions. Dazukibart dose adjustments failed to sustainably control IFN I signaling. Subsequent combination therapy of baricitinib and tocilizumab proved partially effective. Treatment with anifrolumab, an IFNα/β receptor (IFNAR1) blocker, in conjunction with tocilizumab, led to sustained suppression of IFN I scores, allowed discontinuation of JAKi, and resulted in significant improvement in vasculitic wounds. This case underscores the challenges in treating SAVI patients and highlights the utility of IFN I scores as a theragnostic biomarker. While high-dose JAKi, and dazukibart failed to achieve sustained control of IFN I signaling, treatment with anifrolumab durably suppressed IFN scores and demonstrated promising efficacy, allowing investigation of the role of IFN I signaling in the disease pathogenesis of SAVI and other interferonopathies in future clinical trials.