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Introduction: STING-associated vasculopathy with onset in infancy (SAVI) is a prototypic type I interferonopathy caused by activating STING1/TMEM173 variants and frequently complicated by interstitial lung disease (ILD). Comparative treatment data remain limited.

Methods: We reviewed 133 published SAVI literature patients for treatment response across therapeutic classes and report one infant with genetically confirmed SAVI (STING1 p.Arg281Trp, homozygous) and severe early-onset ILD treated with ruxolitinib followed by add-on anifrolumab.

Results: Glucocorticoids provided mainly transient control with frequent steroid dependence, whereas conventional DMARDs and non-pathway-specific biologics were largely ineffective. Among targeted therapies, ruxolitinib showed 12/29 improved, 9/29 partial/mixed, and 8/29 failed responses. Baricitinib showed 12/27 improved, 9/27 partial/mixed, 3/27 failed responses, and 3/27 without sufficient information on the outcome. Tofacitinib was less consistent, with 6/16 improved, 4/16 partial/mixed, and 6/16 failed responses. Anifrolumab showed improvement in 6/6 reported exposures, although numbers remain small. Lung disease remained the most difficult organ manifestation, with stabilization more common than reversal once fibrosis was established. Our infant presented in the first year of life, before severe fibrosis had developed, with tachypnoea, increased work of breathing, failure to thrive, and nocturnal home oxygen dependence. Ruxolitinib started at 8 months and produced no measurable clinical improvement. After add-on anifrolumab, monocyte CD169/SIGLEC1 rapidly fell from ~8,600–13,000 antigen/cell to ~1,100, paralleled by improved respiratory rate, oxygen discontinuation, and catch-up growth.

Conclusion: Conventional immunosuppression is largely inadequate in SAVI, whereas pathway-directed treatment is required. Overall, baricitinib and ruxolitinib showed the strongest treatment signal, tofacitinib was less reliable, and IFNAR1 blockade emerged as a promising strategy. Our review and original case support further evaluation of anifrolumab, especially early, before fixed pulmonary fibrosis is established.