Pos1192 Serum CRP and Il-18 Levels Are Useful in Predicting Prognosis in Patients With Adult Onset Still’s Disease

Background: Adult-onset Still's disease (AOSD) is a multisystem autoinflammatory disease with heterogeneous clinical features. IL-18 is mainly produced by activated macrophage lineage cells and plays a central role in the pathogenesis of this disease. However, little is known about factors associated with poor response to initial glucocorticoid and immunosuppressive therapy in patients with this disease, and there is little evidence that serum IL-18 levels are useful as a prognostic factor in AOSD. Objectives: The aim of this study was to identify prognostic factors for poor response to initial GC therapy and immunosuppressive therapy in AOSD and to clarify the role of IL-18 as a disease activity marker and prognostic factor in AOSD. Methods: We retrospectively reviewed the medical records of patients with AOSD diagnosed between January 2004 and October 2023 at Kurashiki Central Hospital (Kurashiki, Japan). Definitive diagnosis of AOSD was made according to the Yamaguchi criteria. Clinical and laboratory data, including serum IL-6 and IL-18 levels when measured, were collected retrospectively. Results: Complete clinical data were available for 46 adult patients diagnosed with AOSD. Twenty-five patients achieved remission after 4 weeks of oral GC with or without a single immunosuppressive drug. Refractory AOSD patients had higher levels of serum CRP, ferritin, AST and ALT than non-refractory AOSD patients. We performed ROC curve analysis to investigate the ability of serum CRP levels to predict refractory AOSD. The area under the ROC curve was 0.756 (95 %CI: 0.605-0.907, p=0.003) and analysis of the AUC showed that the best cut-off for serum CRP level was 10.23 mg/dl for predicting refractory AOSD with a sensitivity of 81.0% and a specificity of 72.0%. Serum IL-18 and IL-6 levels were measured in 25 and 16 patients with AOSD, respectively. IL-18 serum levels were significantly higher in AOSD patients than in other diseases with HPS. IL-18 levels remained high in AOSD patients even after resolution of clinical symptoms and other abnormal laboratory data, including serum CRP, ferritin and IL-6 levels. Those who had experienced flares at any time during their disease tended to have higher IL-18 than those who had not, even during clinically inactive disease. We experienced two episodes of MAS in two patients under tocilizumab (TCZ) treatment. The patient who developed MAS on TCZ had a significantly higher IL-18/CRP ratio at the start of TCZ (baseline) than other AOSD patients on TCZ. Conclusion: In this retrospective cohort of AOSD patients, higher CRP levels were a prognostic factor for poor treatment outcome at week 4. Changes in IL-18 may reflect increased disease activity, and IL-18 levels during the inactive phase of the disease may correlate with history of MAS, refractory disease and flares in AOSD patients. REFERENCES: [1] Yamaguchi M. et al Preliminary criteria for classification of adult Still's disease. J Rheumatol 19(3):4. [2] Holger Kudela. et al Comparative study of Interleukin-18 (IL-18) serum levels in adult onset Still's disease (AOSD) and systemic onset juvenile idiopathic arthritis (sJIA) and its use as a biomarker for diagnosis and evaluation of disease activity. BMC Rheumatol. 2019; 28: 3: 4. Acknowledgements: NIL. Disclosure of Interests: None declared.