Serum itaconate levels and treatment-related changes in polymyalgia rheumatica: a prospective observational study

Objectives Itaconate (ITA) is an immunometabolic regulator, but its circulating levels and treatment-associated changes in polymyalgia rheumatica (PMR) remain unclear. This study investigated serum ITA levels across treatment states and their longitudinal associations with inflammatory markers and glucocorticoid (GC) exposure. Methods This prospective observational study included 161 serum samples from 108 participants, comprising 20 healthy control (HC), 30 treatment-naïve (TN), and 111 treatment-exposed (TE) samples. Serum ITA was quantified by LC–MS/MS. Between-group differences were assessed using age- and sex-adjusted linear mixed-effects models. Paired changes were evaluated in 11 patients, and longitudinal associations were examined across 42 TE-to-TE intervals from 27 patients using regression models with patient-clustered robust standard errors. Results Adjusted geometric mean ITA concentrations were 4.170 ng/mL (95% CI, 3.132–5.553) in HC, 0.907 ng/mL (0.719–1.143) in TN, and 3.885 ng/mL (3.427–4.405) in TE. ITA levels were significantly lower in TN than in HC and TE (both P<0.001), whereas no significant difference was observed between TE and HC (P = 0.656). Among 11 paired patients, ITA increased in 10 at the first post-treatment follow-up, with median concentrations rising from 1.408 to 5.394 ng/mL (P = 0.0049). Across all 42 treated intervals, changes in ITA were not significantly associated with changes in ESR (P = 0.622). However, among 21 intervals involving abnormal ESR, an inverse association was observed after adjustment for concurrent GC dose changes (β=−0.601, 95% CI, −1.000 to −0.201; P = 0.006; Holm-adjusted P = 0.018). Conclusion Serum ITA was markedly reduced in TN PMR and increased following treatment initiation. Its exploratory inverse association with ESR changes in intervals involving abnormal ESR suggests treatment-associated immunometabolic variation that warrants further investigation.