SAT0519 DRUG RETENTION RATES OF BIOLOGICAL AGENTS IN ADULT ONSET STILL’S DISEASE IN THE PRE-CANAKINUMAB ERA

Abstract

Background:Adult onset Still’s disease (AOSD) is a rare systemic inflammatory disease. Glucocorticoids represents first-line therapy and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) play a central role as steroid-sparing agents. Patients refractory to csDMARD may require the introduction of a biological DMARD (bDMARD). There is paucity of data about the efficacy and drug retention rate (DRR) of bDMARDs used in the treatment of AOSD.Objectives:To retrospectively evaluate DRR and reasons for discontinuation of five different bDMARDs in a monocentric cohort of AOSD patients in a real-world setting.Methods:AOSD patients followed at our Center who received at least one bDMARD were selected. Data about disease duration, number of bDMARDs, reasons for bDMARDs discontinuation, concomitant csDMARDs were collected. Survival curves were determined by the Kaplan-Meier method and compared using a stratified log-rank test. 24-month DRRs were then calculated. Hazard ratio (HR) for previous bDMARDs was also evaluated.Results:We identified 42 patients and 79 bDMARD-courses (Table 1). Anakinra (ANK, n = 41) was the most used bDMARD, followed by tocilizumab (TCZ, n=21) and Tumor Necrosis Factor inhibitors (TNFi, n = 17). At bDMARDs initiation, all patients were being given prednisone (mean dose, 23 ± 18 mg/day) and 76% were on concomitant csDMARD therapy. 36 (46%) treatment courses were stopped by 24 months; discontinuation causes are shown inTable 2. 14 treatment courses were started in the previous 24 months (ANK = 9, TCZ = 5), without being stopped before the study time but not reaching 2-year treatment duration. Overall retention rates at 24 months were the following: TCZ, 62.5%; ANK, 53.1%; TNFi, 11.8% (p = 0.021). Survival curves are shown inFigure 1. DRRs of ANK and TCZ were statistically comparable (p = 0.576), and they were both significantly higher than the DRR of TNFi (p = 0.015). Previous bDMARDs therapy showed no effect on DRR (HR 0.73, 95% CI = 0.40 - 1.31, p = 0.288).Table 1.Clinical characteristics at initiation of biologic agents in adult onset Still’s Disease. TNFi = Tumor Necrosis Factor inhibitorsAnakinra (n=41)Tocilizumab (n=21)TNFi (n=17)p - valueAge (years)38 ± 1643 ± 1938 ± 130.601Female sex (%)61%48%35%0.443Mean disease duration (months)49 ± 6072 ± 7561 ± 640.445Systemic disease (%)61%38%29%0.213C-reactive protein (mg/l)99 ± 84111 ± 10066 ± 520.445Erythrocyte sedimentation rate (mm/h)71 ± 3265 ± 2777 ± 410.617White blood cells (cells/ul)14640 ± 454014116 ± 372416870 ± 55040.361Ferritin (ng/ml)10114 ± 186576327 ± 80616295 ± 95730.591Previous therapy (%)100%100%100%1.000csDMARD (%)88%90%94%0.973bDMARD (%)22%81%59%0.003Mean prednisone dose (mg die)20.3 ± 18.115.8 ± 14.427.3 ± 14.40.252Concomitant csDMARD therapy (%)71%71%59%0.865Table 2.Causes of treatment discontinuation of biologic agents in adult onset Still’s Disease. TNFi = Tumor Necrosis Factor inhibitorsAnakinra (n=41)Tocilizumab (n=21)TNFi (n=17)Total (n=79)Inefficacy24%14%65%30%Adverse events10%10%24%13%Other reasons 2% 5% 0% 3%Total37%29%88%46%Figure 1.Kaplan-Meier curves comparing anakinra (ANK), tocilizumab (TCZ) and Tumor Necrosis Factor inhibitors (TNFi) at 24 months in adult onset Still’s disease.Conclusion:In our AOSD cohort, DRRs at 24 months of TCZ and ANK were not statistically different, and they were both significantly higher than the DRR of TNFi. Previous use of biologic agents was found to have no effect on bDMARDs retention probability.