Biological and targeted synthetic treatment of SAPHO syndrome: systematic literature review.

INTRODUCTION: SAPHO syndrome is a rare autoimmune/autoinflammatory disorder with no approved therapies or standardized management guidelines. Biologic and targeted synthetic DMARDs (b/tsDMARDs) are increasingly used off-label. OBJECTIVES: This review systematically evaluates the evidence for their efficacy in SAPHO. PATIENTS AND METHODS: A PRISMA-guided search of PubMed was conducted through March 31, 2025. Studies of any design reporting outcomes of b/tsDMARDs in patients with SAPHO fulfilling the modified Kahn criteria were included. Exclusion criteria were non-English language, inaccessible full text, and insufficient treatment details. Data on patient characteristics, drug class, follow-up duration, and treatment response were extracted. Because all included studies were case reports or case series, the risk of bias was not assessed. Treatment responses were summarized using descriptive statistics. RESULTS: Of 1,610 screened records, 106 studies comprising 385 instances of b/tsDMARD use met the inclusion criteria; no randomized controlled trials were identified. TNF inhibitors were used in 203 patients, with complete skeletal and skin responses in 81% and 72%, respectively. JAK inhibitors (77 patients) were associated with reported complete response rates of 89% (skeletal) and 94% (skin). Other b/tsDMARD classes-including IL-17, IL-23, IL-1, and IL-6 inhibitors, as well as PDE4 inhibitors-demonstrated variable and generally lower efficacy. CONCLUSIONS: Evidence for b/tsDMARDs in SAPHO remains limited to low-quality, uncontrolled studies with substantial heterogeneity and probable publication bias. TNF and JAK inhibitors are among the most consistently effective therapies reported in the available literature, but high-quality research, including randomized trials or prospective registries, is urgently needed to inform evidence-based management.