AB0353 COMPARATIVE STUDY OF PATIENT BACKGROUND AND TREATMENT OUTCOME BY BARICITINIB DOSE UNDER REAL CLINICAL CONDITIONS.
Authors: T. Nishiume, N. Takahashi, T. Kojima, S. Asai, K. Terabe, N. Ishiguro
Journal: Annals of the Rheumatic Diseases (2020)

Background: Balicitinib (BAR) is one of the Janus kinase (JAK) inhibitors, which mainly inhibits JAK1 and JAK2 and has an anti-inflammatory effect on rheumatoid arthritis(RA). In Japan, it is necessary to use different doses of BAR depending on the RA patient’s estimated glomerular filtration rate (eGFR). The RA-BEACOM and RA-BUILD trials reported the treatment effects by BAR dose at 24 weeks and concluded that there was no difference in DAS(disease activity score)28CRP between BAR 2mg and 4mg. The patient background treated in these double-blind RCTs is uniform even at different BAR doses.There is uncertainty about the difference in the therapeutic effects of BAR dose under the real clinical setting where the patient background differs from that of the trial patients. Objectives: To compare patient backgrounds and treatment outcome by Baricitinib dose under real clinical setting. Methods: 113 RA patients taking BAR who were registered in the Nagoya University Orthopedic Surgery Multicenter Study (TBCR) were included in this study. Patient characteristics (such as age, illness duration, combined anti-rheumatic drugs, eGFR) and DAS28CRP, clinical and simplified disease activity index(CDAI, SDAI respectively) up to 24 weeks were compared between BAR 2mg and 4mg groups. The continuation rates, including the discontinuation due to ineffectiveness and adverse events (AEs), were also compared between the two groups. For these comparisons, Student’s t-test and Pearson’s chi-square test, Kaplan-Meier survival curve were used. Missing data due to discontinuation of BAR was complemented by LOCF method and analyzed statistically. The significance level was set to less than 0.05. Results: There were 39 subjects (8 males and 31 females) in BAR2mg group and 74 patients (17 males and 57 females) in BAR4mg group. There was a significant difference in mean age (73.5 vs. 62.3 years old, p &lt;0.001), average eGFR (65.1vs 84.8ml / min / 1.73m 2 , p &lt;0.001), methotrexete(MTX) use rate (28 vs 58%, p &lt;0.01), average MTX dose (3.0 vs 5.5mg, p &lt;0.01),glucocorticoid(GC) use rate(51.3 vs 33.8%, p &lt;0.01) between the two groups(Table). DAS28CRP improved from week 0 (3.2 vs 3.5) to week 24 (2.5 vs 2.4), and no significant difference was observed between the two groups at each time point (Fig.1-A). The same was true for CDAI and SDAI(Fig.1-B,-C). The rate of DAS28CRP remission and low disease activity was not significantly different at 24 weeks (0.64 vs. 0.69, Fig.1-D). The same was true for CDAI and SDAI(Fig.1-E,-F). Kaplan-Meier analysis showed that there was no difference in discontinuation rate due to ineffectiveness in the two groups. The same was true for the discontinuation rate due to AEs (Figure 2-B,-C). The total continuation rate including discontinuation due to ineffectiveness and AEs was significantly lower in BAR2mg group (0.691 vs 0.843, p &lt;0.05, Fig.2-A). Conclusion: BAR2mg group under real clinical setting was older and had lower eGFR than BAR4mg group. Although the treatment effect for 24 weeks was similar, safety management was considered more important because the discontinuation rate due to AEs tended to be higher in BAR2mg group. References: [1]Taylor PC, (2017) The New England journal of medicine. 376(7), 652. [2]Takeuchi T, Ann Rheum Dis 2019;78:171–178. [3]Keystone EC, Ann Rheum Dis 2015;74:333–340 Table 1. ITT outcomes at week 13 BAR2mg (n=39) BAR4mg (n=74) p value Age, years old 73.5±9.7 62.3±12.6 &lt;0.001 Female 31(79) 57(77) 0.767 Disease duration, year 13.7±11.3 14.2±15.4 0.857 Stage(1/2/3/4) 6/17/8/8 15/24/14/21 0.473 ACPA &gt;4.5U/ml 29(74.4) 59(79.7) 0.629 eGFR, ml/min/1.73m 2 65.1±27.7 84.8±23.2 &lt;0.001 MTX dose, mg/week 3.03±4.83 5.54±5.48 0.018 MTX use 11(28.2) 41(55.4) 0.003 GC dose, mg/day 1.91±2.36 1.32±2.20 0.191 GC use 20(51.3) 25(33.8) 0.007 DAS28CRP 3.42±1.04 3.52±13.0 0.689 CDAI 12.6±7.6 15.1±10.9 0.222 SDAI 14.7±9.7 16.2±11.4 0.279 Values are the mean±SD or the number (%). Disclosure of Interests: Tsuyoshi Nishiume: None declared, Nobunori Takahashi Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Ono, Pfizer, Takeda, and UCB Japan, Toshihisa Kojima Grant/research support from: Chugai, Eli Lilly, Astellas, Abbvie, and Novartis, Consultant of: AbbVie, Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda, Shuji Asai Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Janssen, Takeda, and UCB Japan, Kenya Terabe: None declared, Naoki Ishiguro Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi-Sankyo, Eisai, Kaken, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and Zimmer Biomet, Consultant of: Ono, Speakers bureau: Astellas, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, and Taisho Toyama