ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1325

Prevention of Joint Destruction in Patients with High Disease Activity or High C-Reactive Protein

Yoshiya Tanaka1, Masayoshi Harigai2, Tsutomu Takeuchi3, Hisashi Yamanaka4, Naoki Ishiguro5, Kazuhiko Yamamoto6, Yutaka Ishii7, Daniel Baker8, Nobuyuki Miyasaka9 and Takao Koike10, 1The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan, 2Dept of Pharmacovigilance, Tokyo Medical and Dental University, Tokyo, Japan, 3Keio University School of Medicine, Tokyo, Japan, 4Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, 5Department of Orthopedic Surgery, Nagoya University, Graduate School & Faculty of Medicine, Nagoya, Aichi, Japan, 6Department of Allergy & Rheumatology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan, 7Medical Affaires, Janssen Pharmaceutical K.K, Tokyo, Japan, 8Janssen Research & Development, LLC., Spring House, PA, 9Department of Medicine and Rheumatology and Global Center of Excellence Program, Tokyo Medical and Dental University, Tokyo, Japan, 10Sapporo medical center NTT EC, Sapporo, Japan

Meeting: ACR/ARHP Annual Meeting 2012

Keywords: ,

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy

Session Type: Abstract Submissions (ACR)

Prevention of Joint Destruction in Patients with High Disease Activity or High C-reactive protein

Background/Purpose: In Japan, 2 doses (50mg and 100mg) of golimumab (GLM) were approved for the treatment of rheumatoid arthritis (RA) patients (pts), used with methotrexate (MTX), based on the results from GO-FORTH study. However, differences in joint destruction between the GLM 100mg and 50mg groups remain unclear. In a sub analysis of the GO-FORTH study, we assessed the difference of suppression on joint destruction progression between 100mg and 50mg based on the baseline disease activity or CRP.

Methods: GO-FORTH is a multicenter, randomized, double-blind, placebo(PBO)-controlled study in pts with active RA despite MTX. Pts were randomized to SC PBO, GLM50 mg, or GLM100 mg q4wks. All pts received MTX 6-8 mg orally/wk. Pts with <20% improvement in SJC/TJC entered early escape(EE) at wk 16 so that PBO→GLM50 mg and GLM50 mg→GLM100 mg. Pts who did not enter EE continued initial therapy until wk 24. The DTSS and inhibition rates (IR, DTSS ≤ 0) on progression of joint destruction through wk 24 in MTX-resistant pts (n=261) by baseline DAS28ESR and CRP were compared. High disease activity pts (HDA) and high CRP pts were defined as DAS28ESR > 5.1 or CRP ≥ 1.5mg/dL, and moderate disease activity pts (MDA) and low CRP were defined as 3.2 < DAS28 (ESR) ≤ 5.1 or CRP < 1.5mg/dL.

Results: Mean DTSS (median) in placebo + MTX with HDA (n=57) or high CRP (n=40) were 3.48 (1.0) and 3.41 (1.0) which were higher than those in MDA (0.76 (0.0) (n=29)) and low CRP (1.76 (0.0) (n=48)), respectively (Table). In HDA and high CRP, mean DTSS in GLM 100mg + MTX was lower compared with GLM 50mg + MTX in HDA and high CRP individually, although MDA and low CRP were not. IR on progression in HDA and high CRP were 40.4% in placebo + MTX (n=57), 43.1% in GLM 50mg + MTX (n=51) and 69.8% in 100mg + MTX (n=53) by HDA, and 40.0% (n=40), 38.2% (n=34) and 61.5% (n=26) by high CRP, respectively. IR on progression in MDA and low CRP were 69.0% (n=29), 81.8% (n=33) and 70.6% (n=34) by MDA and 58.3% (n=48), 73.1% (n=52) and 73.8% (n=61) by low CRP, respectively. Group differences in IR were only observed between GLM 50mg + MTX and 100mg + MTX in HDA or high CRP. The suppression on joint destruction in GLM 50mg + MTX was effective in MDA or low CRP, however it was not effective in HAD or high CRP. Pts whose DTSS >0 in GLM 50mg + MTX with HAD or high CRP had short disease duration and small TSS as baseline characteristics in comparison with pts whose DTSS ≤ 0.

Conclusion: In the GO-FORTH study, joint destruction progression in RA pts with HAD or high CRP at baseline was more rapid than in RA pts with MDA or low CRP. GLM 100mg was more effective in preventing joint destruction than GLM 50mg, especially in RA pts with early and high disease activity or high CRP.

Table: Change from baseline in vdH-S through wk 24.

 

 

 

 

Placebo + MTX†

50mg + MTX

100mg + MTX

Overall

number of patients

88

86

87

 

Dtotal vdH-S score

 

 

 

 

mean (SD)

2.51 (5.52)

1.05 (3.71)

0.33 (2.66)

 

median (min, max)

0.25 [-8.5, 33.5]

0.00 [-6.3, 22.5]

0.00 [-3.5, 19.0]

 

p value

–

0.0203

0.0006

 

Change in vdH-S score £ 0

44 (50.0%)

51 (59.3%)

61 (70.1%)

 

p value

–

0.2179

0.0066

DAS28(ESR)

number of patients

29

33

34

>3.2 – ≤5.1

Dtotal vdH-S score

 

 

 

 

mean

0.76

-0.27

0.23

 

median (min, max)

0.00 [-1.5, 8.0]

0.00 [-3.5, 3.5]

0.00 [-3.5, 6.2]

 

p value

–

0.0257

0.1977

 

Change in vdH-S score £ 0

20 (69.0%)

27 (81.8%)

24 (70.6%)

 

p value

–

0.2384

0.8888

>5.1

number of patients

57

51

53

 

Dtotal vdH-S score

 

 

 

 

mean

3.48

1.94

0.39

 

median (min, max)

1.00 [-8.5, 33.5]

0.50 [-6.3, 22.5]

0.00 [-3.5, 19.0]

 

p value

–

0.1127

0.0012

 

Change in vdH-S score £ 0

23 (40.4%)

22 (43.1%)

37 (69.8%)

 

p value

–

0.7069

0.0019

CRP (mg/dL)

number of patients

48

52

61

<1.5

Dtotal vdH-S score

 

 

 

 

mean

1.76

-0.04

0.02

 

median (min, max)

0.00 [-1.5, 19.5]

0.00 [-6.3, 5.5]

0.00 [-3.5, 7.0]

 

p value

–

0.0010

0.0007

 

Change in vdH-S score £ 0

28 (58.3%)

38 (73.1%)

45 (73.8%)

 

p value

–

0.1200

0.0889

>1.5

number of patients

40

34

26

 

Dtotal vdH-S scor

 

 

 

 

mean

3.41

2.71

1.15

 

median (min, max)

1.00 [-8.5, 33.5]

1.00 [-4.5, 225]

0.00 [-2.0, 19.0]

 

p value

–

0.6021

0.1151

 

Change in vdH-S score £ 0

16 (40.0%)

13 (38.2%)

16 (61.5%)

 

p value

–

0.8768

0.0871

Data shown are number (%) of patients or mean ±SD, median [range].

 

 

P values derived from comparisons versus placebo+MTX. Dtotal vdH-S score was tested by van der Waerden normal scores. Changes in vdH-S score £ 0 was tested by chi-square test.

†Pts with <20% improvement in SJC/TJC entered early escape(EE) at wk 16 so that PBO→GLM50 mg and GLM50 mg→GLM100 mg.

 

Disclosure:

Y. Tanaka,

Janssen Research and Development, LLC,

9;

M. Harigai,

Janssen Research and Development, LLC,

9;

T. Takeuchi,

Janssen Research and Development, LLC,

9;

H. Yamanaka,

Janssen Research and Development, LLC,

9;

N. Ishiguro,

Janssen Research and Development, LLC,

9;

K. Yamamoto,

Janssen Research and Development, LLC,

9;

Y. Ishii,

Janssen Pharmaceutical K.K,

3;

D. Baker,

Janssen Research and Development, LLC,

3;

N. Miyasaka,

Janssen Research and Development, LLC,

9;

T. Koike,

Janssen Research and Development, LLC,

9.

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