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 disease-modifying antirheumatic drugs (b/tsDMARDs) are increasingly used off‑label. OBJECTIVES: This review aimed to systematically evaluate the evidence for the efficacy of b/tsDMARDs in SAPHO. PATIENTS AND METHODS: A PRISMA‑guided search of PubMed database 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. As all the included studies were case reports or case series, the risk of bias was not assessed. Treatment responses were summarized using descriptive statistics. RESULTS: Of 1610 screened records, 106 studies comprising 385 instances of b/tsDMARD use met the inclusion criteria; no randomized controlled trials were identified. Tumor necrosis factor inhibitors (TNFis) were used in 203 patients, with complete skeletal and skin responses in 81% and 72%, respectively. The use of Janus kinase inhibitors (JAKis) in 77 patients was associated with complete response rates of 89% (skeletal) and 94% (skin). Other b/tsDMARD classes-including interleukin 17 (IL‑17), IL‑23, IL‑1, and IL‑6 inhibitors, as well as phosphodiesterase‑4 inhibitors-demonstrated variable and generally lower efficacy. CONCLUSIONS: Evidence for b/tsDMARD efficacy in SAPHO remains limited to low‑quality, uncontrolled studies with substantial heterogeneity and probable publication bias. TNFis and JAKis 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.