AB0358 REDUCTION OF WHITE BLOOD CELL COUNT PREDICTS THE EFFICACY OF BARICITINIB, DOES NOT OF TOFACITINIB FOR RHEUMATOID ARTHRITIS.
Authors: M. Sugihara, N. Yokogawa, K. Shimada
Journal: Annals of the Rheumatic Diseases (2020)

Background: Pairing Janus kinase (JAK) 1/JAK3 signaling mediates lymphocyte proliferation and differentiation while pairing JAK2/JAK2 signaling is essential in myelopoiesis, erythropoiesis, and platelet production by facilitating signaling mediated by granulocyte-macrophage colony stimulating factor and erythropoietin. Tofacitinib (TOF) preferentially inhibits JAK1 and JAK3, while baricitinib (BAR) inhibits JAK1 and JAK2 in vitro (1). However, the difference in the efficacy and the clinical courses between TOF and BAR in patients with rheumatoid arthritis (RA) remains unclear. Objectives: The objective of this study was to compare TOF and BAR in efficacy and changes in peripheral blood cell counts. We hypothesized that the efficiency of BAR was related to the decline in the blood cell counts, but that of TOF was not in patients with RA. Methods: We conducted a multicenter, 24 week-retrospective observational study. All RA patients received TOF (n = 43) or BAR (n = 26) treatment at Tama-Hokubu Medical Center and Tama Medical Center from December 2013 to March 2019 were included. Results: Baseline characteristics were similar between both groups; age 59.1 and 65.0 years old, disease duration 164.1 and 111.7 months, C-reactive protein 1.98 and 2.22 mg/ml, rheumatoid factor positive 76.7 % and 84.0 %, anti-citrullinated peptide antibody positive 78.9 % and 78.8 %, methotrexate combination 81.4 % and 69.2 %, the number of previous treatment of biologic or targeted disease-modifying antirheumatic drugs were 2.7 and 2.8, for TOF and BAR, respectively (mean). Simplified Disease Activity Index (SDAI) at baseline were similar between the groups (TOF 20.77, BAR 19.15). There was no significant difference in efficacy between the both groups at week 24 (SDAI remission: TOF 3 (7%), BAR 6 (23.1%), p = 0.054, SDAI low disease activity (LDA): TOF 21 (48.8%), BAR 17 (65.4%), p = 0.181). Among those who achieved SDAI LDA at week 24 in the BAR group, significant decrement of white blood cell (WBC) counts at week 12 and 24 and of neutrophil counts at week 4, 12 and 24 were observed (p &lt; 0.05, Table). These decrements of cell count were not observed in patients who did not achieve LDA or in patients in the TOF group. Platelets and hemoglobin (data not shown) had no significant change in all groups. Conclusion: Clinical efficacy of TOF and BAR in RA was comparable in our cohort. A significant decrease of WBCs and neutrophils was associated with LDA achievement at week 24 in the BAR group. This could be explained by the inhibition of myelopoiesis through JAK2 signaling. References: [1]Winthrop, K. Nat Rev Rheumatol 13, 234–243 (2017) Table 1. Description of the three clusters tofacitinib baricitinib week LDA p not LDA p LDA p not LDA p White Blood Cells [/µl] 0 6821 ± 2402 6041 ± 2612 7994 ± 4309 7886 ± 2513 4 6247 ± 1905 .254 6465 ± 2440 .344 6706 ± 2499 .059 7143 ± 1526 .363 12 6480 ± 1949 .497 5871 ± 2070 .217 6470 ± 2867 .031 7383 ± 2963 .356 24 6733 ± 2297 .858 6450 ± 3001 .428 6418 ± 2875 .024 6833 ± 1021 .454 Neutrophils [/µl] 0 4888 ± 2399 3982 ± 2300 6221 ± 4085 6221 ± 4085 4 4243 ± 1655 .210 4298 ± 2100 .461 4548 ± 2578 .015 5923 ± 2716 .294 12 4261 ± 1843 .324 3617 ± 1869 .236 4542 ± 3062 .019 5429 ± 3055 .311 24 4487 ± 2243 .657 4547 ± 2847 .190 4225 ± 2900 .008 4474 ± 1396 .207 Lymphocytes [/µl] 0 1419 ± 651 1305 ± 489 1370 ± 416 1395 ± 485 4 1515 ± 544 .357 1502 ± 514 .039 1730 ± 659 .013 1530 ± 652 .484 12 1537 ± 555 .523 1327 ± 664 .996 1569 ± 572 .011 1453 ± 401 .832 24 1511 ± 598 .697 1143 ± 378 .092 1792 ± 699 .011 1836 ± 710 .109 Platelets [10 4 /µl] 0 26.9 ± 9.1 23.7 ± 6.6 30.3 ± 11.2 26.9 ± 7.4 4 25.5 ± 8.9 .291 23.8 ± 6.6 .940 30.5 ± 4.6 .940 27.3 ± 10.8 .798 12 24.7 ± 7.4 .261 25.6 ± 7.5 .209 33.1 ± 8.3 .209 27.0 ± 9.3 .905 24 26.3 ± 8.1 .930 23.3 ± 6.1 .961 33.4 ± 6.9 .961 33.0 ± 4.4 .063 Data are mean ± standard deviation. LDA: patients achieved SDAI LDA at week 24. not LDA: patients did not achieve SDAI LDA at week 24. Shown p values were calculated by t-test compared to week 0. Disclosure of Interests: None declared