SAT0124 RISK OF SERIOUS INFECTION, MALIGNANCY, OR DEATH IN JAPANESE RHEUMATOID ARTHRITIS PATIENTS TREATED WITH A COMBINATION OF ABATACEPT AND TACROLIMUS: A RETROSPECTIVE COHORT STUDY
Authors: K. Tokunaga, K. Matsui, H. Oshikawa, T. Matsui, S. Tohma
Journal: Annals of the Rheumatic Diseases (2020)

Background: Both Abatacept (ABT) and Tacrolimus (Tac) suppress T cell immunity, but it is unknown whether combinations of these will increase the risk of adverse events. Objectives: To evaluate whether combining ABT and Tac increases the risk of infection and malignancy compared to their individual use in Japanese rheumatoid arthritis (RA) patients. Methods: We conducted a retrospective cohort study of RA patients using the multicenter database in Japan (NinJa). The dataset was clinical information at a certain point within each year, and the point was any point selected by a registered physician. RA was clinically diagnosed in the dataset. (1) We analyzed the data from RA patients registered in NinJa during the period from April 2010 to March 2019. In this study, we compared three groups who received Tac, ABT or a combination of both. We included patients who had just begun initiating treatment with ABT or Tac, and we excluded patients who used TNF inhibitors, IL-6 inhibitors, and Jak inhibitors in the first year. The primary outcome was defined the composite events including infections that require hospitalization, newly diagnosed malignancy, and death from any cause after initiation of ABT or Tac. We assessed whether the combination contributed to increase the risk of outcome by performing a Cox regression analysis. Results: Among the 27032 RA patients in the registry, 2009 patients were included. The Tac, ABT and combination groups consisted of 1328, 563 and 118 patients, respectively. (Figure 1) (Table 1) Primary outcomes occurred in 149 (13.4%), 62 (13.5%), 14 (13.9%) patients, of the Tac, ABT and combination groups, respectively. The incidence between groups was not significantly different (p= 0.638). (Figure 2) A Cox regression analysis was adjusted for the following parameters: age, sex, disease duration, modified health assessment questionnaire, disease activity score 28-CRP, CRP, use of prednisolone, and use of methotrexate. The analysis revealed no significant differences between groups. The hazard ratio (95% confidence interval) was as follows: Tac 1.00 (Ref), ABT 1.02 (0.74-1.40), and combination 1.15 (0.65-2.05). Table 1. baseline characteristics Tacrolimus Abatacept Combination p value N (person-year) 1328 (2505) 563 (944) 118 (193) age (median [IQR]) 69.00 [60.00, 76.00] 70.00 [61.00, 76.00] 67.00 [59.00, 74.00] 0.169* sex female (%) 1038 (78.2) 468 (83.1) 97 (82.2) 0.039† disease duration (yr) (median [IQR]) 9.00 [4.00, 18.00] 11.00 [5.00, 21.00] 11.00 [7.00, 20.00] 0.002* Steinbrocker stage (%) I 285 (23.5) 82 (15.6) 12 (12.1) &lt;0.001† II 361 (29.8) 125 (23.8) 25 (25.3) III 232 (19.1) 150 (28.5) 31 (31.3) IV 334 (27.6) 169 (32.1) 31 (31.3) mHAQ (median [IQR]) 0.25 [0.00, 0.75] 0.38 [0.00, 1.00] 0.50 [0.00, 1.13] &lt;0.001* DAS28CRP (median [IQR]) 2.58 [1.88, 3.40] 2.77 [2.09, 3.62] 3.01 [2.27, 3.98] &lt;0.001* CRP (mg/dL) (median [IQR]) 0.30 [0.10, 1.02] 0.35 [0.13, 1.10] 0.30 [0.14, 0.82] 0.590* RF positivity (%) 708/895 (79.1) 331/400 (82.8) 57/71 (80.3) 0.314† Tacrolimus (mg/d) (median [IQR]) 1.50 [1.00, 2.00] 0.00 [0.00, 0.00] 2.00 [1.00, 2.50] &lt;0.001* MTX use (%) 619 (46.6) 264 (46.9) 32 (27.1) &lt;0.001† PSL use (%) 749 (56.4) 299 (53.1) 71 (60.2) 0.253† Abbreviations: anti-CCP, anti-cyclic citrullinated peptide; mHAQ, modified Health Assessment Questionnaire; MTX, methotrexate; PSL, prednisolone; RF, rheumatoid factor * Kruskal-Wallis test; † chi square test; ‡ analysis of variance (ANOVA) Conclusion: The combination of ABT and Tac does not increase the risk of adverse events in patients with rheumatoid arthritis in Japan when compared to the use ABT or Tac alone. Further evaluation is needed. References: [1]Matsui T, et al. Ann Rheum Dis 2007;66:1221–6. Disclosure of Interests: Kenichiro Tokunaga: None declared, Kunihiko Matsui: None declared, Hideto Oshikawa: None declared, Toshihiro Matsui Paid instructor for: Chugai Pharmaceutical Co., LTD., Janssen Pharmaceutical K,K,, Shigeto Tohma: None declared