AB0400 Open Labeled, Multicenter 24-Week Study To Assess The Efficacy and Safety of Tacrobell® in Active Rheumatoid Arthritis Patients
Authors: S.-J. Hong, J.-Y. Choi, S.-S. Kim, Y.S. Kim, S.-H. Kim, G.-T. Kim, S.J. Choi, M.S. Lee, J.-W. Hur
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Rheumatoid arthritis (RA) is chronic inflammatory disease characterized by persistent synovitis and structural joint damage with T cell-driven inflammation. Tacrolimus suppress activation of T cells through the inhibition of calcineurin. <h3>Objectives</h3> We evaluated the efficacy and safety of Tacrobell® (Tacrolimus from Chong Kun Dang Pharma Inc.) in Korean active RA patient who had inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) including Methotrexate (MTX). <h3>Methods</h3> During the study period from Aug. 2012 to Jun. 2015, in this open labeled, multicenter study, 111 patients were enrolled. Patients were in active disease state with Disease Activity Score28 (DAS28) ≥3.2 despite previously taken at least one conventional DMARD including MTX. Patients had wash out period with DMARDs, except MTX. Patients received Tacrobell® during 24 weeks. The initial dose was 1 mg once daily and was increased to 3mg once daily by 1mg, every 4 weeks. The disease activity was measured by the DAS28-ESR at 4, 8, 16, 24-week after the add on Tacrobell®. Simplified Disease Activity Index (SDAI), Korean Health Assessment Questionnaire (KHAQ)-20, Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP) and the safety was assessed. <h3>Results</h3> Data from 97 patients were evaluated in full set analysis. At week-24, EULAR response rate were 83.5% (81 of 97) with improvements from week-16 in 74.2% (72 of 97). Mean DAS28-ESR was continuously decreased of 5.64 at baseline, 4.14 (±1.22, <i>p</i>&lt;0.001) at week-16 and 3.66 (±1.39, <i>p</i>&lt;0.001) at week-24. Efficacy rates according to SDAI were 89.7% (87 of 97) and KHAQ-20 score decreased -2.42 (±4.37, <i>p</i>&lt;0.001) from baseline 7.27 (±4.59) at week-24. Mean ESR was decreased -10.97 (±24.16, <i>p</i>&lt;0.001) at week-16, -14.77 (±24.57, <i>p</i>&lt;0.001) at week-24 from baseline 46.05 (±23.22). Mean CRP was decreased from 2.86 (±7.85, <i>p</i>=0.0578) at baseline to 1.34 (±3.02, <i>p</i>=0.0367) at week-24. The most common adverse events were in gastrointestinal (18 of 108; 16.679%) and respiratory disorder (12 of 108; 16.67%). In serious adverse events (6 of 108, 5.56%), two cases (pneumonia, high glucose level) were related with Tacrobell® and recovered with treatment. At laboratory exam, no abnormal findings with increased BUN or Cr as known common Tacrolimus side effect. Systolic blood pressure increased 2.12 mmHg at week-8. <h3>Conclusions</h3> This study demonstrated the efficacy of add on Tacrobell® therapy to MTX in patients with active RA. <h3>References</h3> Tsutomu T., et al (2013) Post-marketing surveillance of the safety and effectiveness of tacrolimus in 3,267 Japanese patients with rheumatoid arthritis Mod Rheumatol.; 24(1):8–16 Takeyuki K., et al (2013) Long-term therapeutic effects and safety of tacrolimus added to methotrexate in patients with rheumatoid arthritis Rheumatol Int.; 33:871–877 Mariko K., et al (2013) Efficacy of adjunct tacrolimus treatment in patients with rheumatoid arthritis with inadequate responses to methotrexate Mod Rheumatol.; 23:788–793 Kawai S., et al. (2011) Efficacy and safety of additional use of tacrolimus in patients with early rheumatoid arthritis with inadequate response to DMARDs-a multicenter, double-blind, parallel-group trial Mod Rheumatol.; 21(5):458–68 <h3>Disclosure of Interest</h3> None declared