ACR2014 in Bostonでの発表ポスター。イグラチモドをテーマにしました。名大関連TBCRのデータです。

1. Influences of Disease Activity at the Initiation of Iguratimod, a Small Molecule Antirheumatic
Drug, on Efficacy of Iguratimod in Patients with Rheumatoid Arthritis
Yuji Hirano1, Toshihisa Kojima2, Yasuhide Kanayama3, Shinya Hirabara1, Nobunori Takahashi2, Atsushi Kaneko4 and Naoki Ishiguro2
Background
1Toyohashi Municipal Hospital, 2Nagoya University Graduate School of Medicine, 3Toyota Kosei Hospital, 4Nagoya Medical Center
Iguratimod (IGU), known as T-614, is a small-molecule
antirheumatic drug developed in Japan
and used in Japanese clinical practice since June
in 2012. IGU is an oral tablet drug and sold as
Careram® from Eisai co. Ltd. or Kolbet® from
Taisho Toyama Pharmaceutical Co. Ltd. in Japan.
IGU is known to inhibit nuclear factor-kappa B
activation in cultured human synovial cells.
Although biological agents (BIO) have good
efficacy to treat rheumatoid arthritis (RA), they
costs very much. IGU is not comparatively
expensive and used as monotherapy or
combination therapy with methotrexate (MTX).
Data in clinical practice is lacking and necessary
for the best use of IGU. This retrospective study
investigated efficacy of IGU in RA patients with
focus on disease activity at initiation of IGU using
data from the Japanese multicenter registry
(Tsurumai Biologics Communication Registry plus).
Methods
~ a Multicenter Registry Study TBCR ~
Results
Figure 4: Continuation rate for 24w and reasens of stopping IGU
Figure 5: Comparison of improvement between two groups
Mann-Whitney U-test was used for statistical analysis.
Conclusion
78 cases (62 female and 16 male) with RA from
9 institutes in Japan were treated with IGU and
were included in this study. IGU was prescribed as
25mg/day in 4 weeks and 50mg/day after 4weeks
in most patients according to Japanese regulation.
These patients were divided into two groups (high
disease activity group; HG and moderate and low
disease activity group; MLG) using DAS28-CRP at
initiation of IGU. IORRA definition was used as
thresholds of DAS28-CRP. 42 cases were included
in HG (DAS28-CRP>4.1) and 36 cases were
included in MLG (DAS28-CRP ≦ 4.1). Patients’
characteristics, time course of disease activity
using DAS28-CRP and SDAI, drug retention rate at
24 weeks and absolute value of change and
percentage improvement in disease activity
parameters from 0w to 24w were compared with
each other.
Table 1: Baseline characteristics at the initiation of IGU
HG (n=42) MLG (n=36)
Mean Age (years old)
Female/Male (case)
Mean RA duration (month)
Mean Body Weight (kg)
Stage (I/ II/ III/ IV)
Class (1/ 2/ 3/ 4)
RF>15IU/ml (%)
Concomitant MTX (%)
Mean MTX dose in all (mg/week)
MTX dose in Only MTX-treated
Concomitant PSL (%)
Mean PSL dose (mg/day)
DMARDs numbers including IGU
Biologics-concomitant (case)
Mean DAS28-CRP
Mean SDAI
Tender joint counts
Swollen joints counts
Patients’ global assessment (mm)
Physicians' global assessment (mm)
Mean CRP (mg/dl)
Mean ESR (mm/hour)
MMP-3 (ng/ml)
Health Assessment Questionnaire
P value
68.3
33/9
147
51.3
6/7/12/17
5/15/21/1
92.3
52.4
4.7
9.0
46.3
2.5
2.0
2
4.99
27.9
9.0
4.6
60.1
56.0
2.7
57.5
301.8
1.17
65.7
29/7
94
51.8
11/5/13/7
11/20/5/0
88.6
63.9
5.2
8.1
42.9
1.8
1.8
1
3.24
11.8
2.1
2.1
35.8
29.3
1.1
36.2
185.8
0.64
0.677
0.829
0.062
0.644
0.584
0.305
0.601
0.393
0.761
0.395
0.452
<0.0001
<0.0001
<0.0001
0.0049
<0.0001
<0.0001
<0.0001
0.001
0.0049
0.003
Mann-Whitney U-test or Chi-square test was used for statistical analysis.
DAS28-CRP SDAI
Figure 1: Time course of disease activity (DAS28-CRP & SDAI)
Wilcoxon signed-rank test was used for statistical analysis.
There were statistically significant difference between two groups
at all time point.
*: p<0.05 vs. baseline (0w).
HG MLG
Figure 2: Time course of disease activity criteria using DAS28-CRP
Cut-off value was 4.1-2.7-2.3 according IORRA criteria in Japan.
HG MLG
Figure 3: Time course of disease activity criteria using SDAI
Cut-off value was 26-11-3.3.
More treatment options other than
sufficient MTX and BIO are needed in RA
patients with concomitant disease such as
lung disease or renal dysfunction. High
cost of BIO is another issue to inhibit
improvement of signs and symptoms in RA
patients. This study suggests that IGU is
one of the options in RA patients not only
treated with sufficient MTX but also treated
with insufficient MTX.
Careram® from Eisai co. Ltd. and Kolbet® from Taisho Toyama Pharmaceutical Co. Ltd.
First Author’s Disclosure: Speeking fee from Tanabe Mitsubishi pharma, Pfizer, Eisai, Abbie, Chugai pharmaceutical, Bristol-Myers Squibb, Astellas, UCB Japan, Santen pharma
Corresponding Author: Yuji Hirano from Department of Rheumatology, Toyohashi Municipal Hospital, Toyohashi, Japan, E-mail: yu-hr@sf.commufa.jp