SAT0519 DRUG RETENTION RATES OF BIOLOGICAL AGENTS IN ADULT ONSET STILL’S DISEASE IN THE PRE-CANAKINUMAB ERA
Authors: N. Farina, A. Tomelleri, C. Campochiaro, G. De Luca, G. Cavalli, E. Baldissera, L. Dagna
Journal: Annals of the Rheumatic Diseases (2020)

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 in Table 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 in Figure 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 inhibitors Anakinra (n=41 ) Tocilizumab (n=21 ) TNFi (n=17 ) p - value Age (years) 38 ± 16 43 ± 19 38 ± 13 0.601 Female sex (%) 61% 48% 35% 0.443 Mean disease duration (months) 49 ± 60 72 ± 75 61 ± 64 0.445 Systemic disease (%) 61% 38% 29% 0.213 C-reactive protein (mg/l) 99 ± 84 111 ± 100 66 ± 52 0.445 Erythrocyte sedimentation rate (mm/h) 71 ± 32 65 ± 27 77 ± 41 0.617 White blood cells (cells/ul) 14640 ± 4540 14116 ± 3724 16870 ± 5504 0.361 Ferritin (ng/ml) 10114 ± 18657 6327 ± 8061 6295 ± 9573 0.591 Previous therapy (%) 100% 100% 100% 1.000 csDMARD (%) 88% 90% 94% 0.973 bDMARD (%) 22% 81% 59% 0.003 Mean prednisone dose (mg die) 20.3 ± 18.1 15.8 ± 14.4 27.3 ± 14.4 0.252 Concomitant csDMARD therapy (%) 71% 71% 59% 0.865 Table 2. Causes of treatment discontinuation of biologic agents in adult onset Still’s Disease. TNFi = Tumor Necrosis Factor inhibitors Anakinra (n=41) Tocilizumab (n=21) TNFi (n=17) Total (n=79 ) Inefficacy 24% 14% 65% 30% Adverse events 10% 10% 24% 13% Other reasons 2% 5% 0% 3% Total 37% 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. References: [1]Efficacy and safety of biological agents in adult-onset Still’s disease; Cavalli et al; Scand J Rheumatol. 2015;44(4):309-14. Disclosure of Interests: Nicola Farina: None declared, Alessandro Tomelleri: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Giulio Cavalli Speakers bureau: SOBI, Novartis, Pfizer, Elena Baldissera Speakers bureau: Novartis, Pfizer, Roche, Alpha Sigma, Sanofi, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI