ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1890

Consistent Inhibition of Bone Destruction By Denosumab in Important Subgroups of Japanese Patients with Rheumatoid Arthritis

Naoki Ishiguro1, Yoshiya Tanaka2, Hisashi Yamanaka3, Toshiyuki Yoneda4, Takeshi Ohira5, Naoki Okubo6, Harry K. Genant7, Desiree van der Heijde8 and Tsutomu Takeuchi9, 1Orthopaedic Surgery and Rheumatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2University of Occupational and Environmental Health, Japan, Kitakyushu, Japan, 3Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan, 4Indiana University School of Medicine, Indianapolis, IN, 5Daiich Sankyo Co. Ltd, Tokyo, Japan, 61-2-58, Hiromachi, Daiichi Sankyo Co. Ltd, Tokyo, Japan, 7University of California, San Francisco, CCBR-Synarc, Newark, Tiburon, CA, 8Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 9Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Imaging of Rheumatic Diseases: X-ray, MRI and CT

Session Type: Abstract Submissions (ACR)

Background/Purpose

Denosumab is a fully human monoclonal antibody (IgG2 subclass) that binds specifically to RANKL, inhibits osteoclast-induced bone resorption by preventing the binding of RANKL to RANK, and has been examined in the DRIVE Study to determine its efficacy and safety in Japanese patients with rheumatoid arthritis (RA). The primary endpoint was the change in the bone erosion from baseline to 12 months. Subgroup analyses were undertaken to understand whether denosumab was broadly effective upon progression of the bone erosion in RA patients.

Methods

The DRIVE Study was a 12-month, phase II, randomized, double-blind trial in RA patients receiving methotrexate (MTX) treatment. Patients were randomized to one of four treatment groups which were denosumab (60 mg every 6 months (Q6M), 60 mg every 3 months (Q3M) or 60 mg every 2 months (Q2M)) or placebo. Randomization was stratified by glucocorticoid use and rheumatoid factor (RF) status at screening. All patients basically continued the MTX treatment and a supplement of calcium and vitamin D throughout the study. The bone erosion score was assessed by the modified Sharp-van der Heijde method. Subgroup analyses were conducted according to the risk factors for radiographic damage: RA disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), RF status, anti-cyclic citrullinated peptide (anti-CCP) antibody, swollen joints (SWJ), and glucocorticoid use.

Results

The analysis was performed in 340 patients (88 in placebo, 85 in Q6M, 82 in Q3M and 85 in Q2M). Denosumab significantly inhibited the progression of bone erosion from baseline to 12 months compared to placebo. Changes from baseline in modified Sharp erosion score at 12 months (Mean ± SD) were 0.99 ± 2.69 in placebo, 0.27 ± 0.98 in Q6M (compared to placebo, p=0.0082), 0.14 ± 0.53 in Q3M (p=0.0036), and 0.09 ± 1.52 in Q2M (p<0.0001). The subgroups with risk factors for radiographic damage tended to show consistent results for the primary endpoint in total group.

Change of modified Sharp bone erosion score from baseline to 12 months in subgroups

Placebo

N = 88

Denosumab 60 mg

Q6M
N = 85

Q3M
N = 82

Q2M
N = 85

RA disease duration (years)

< 3

0.68±1.51

0.37±1.09

0.18±0.53

-0.13±0.57

≥ 3

1.65±4.20

0.03±0.64

0.04±0.55

0.59±2.63

CRP (mg/dL)

< 1.0

0.77±1.89

0.16±0.67

0.09±0.51

0.05±1.58

≥ 1.0

1.69±4.35

0.89±1.89

0.42±0.61

0.32±1.03

ESR (mm/hr)

< 28

0.46±1.23

0.07±0.50

 0.01±0.42

0.11±1.80

≥ 28

1.88±3.97

0.81±1.60

0.42±0.64

0.03±0.77

RF status

Positive

1.18±3.08

0.25±0.73

0.21±0.55

0.15±1.83

Negative

0.59±1.53

0.31±1.41

-0.02±0.46

-0.05±0.44

Anti-CCP antibody

Positive

1.30±3.04

0.26±0.75

0.16±0.57

0.09±1.73

Negative

0.07±0.23

0.33±1.73

 0.08±0.39

0.08±0.37

SWJ

< 10

0.59±1.55

0.07±0.63

0.03±0.37

0.14±2.04

≥ 10

1.50±3.61

0.71±1.40

0.25±0.64

0.03±0.53

Glucocorticoid use

Presence

1.37±3.74

0.33±1.24

0.23±0.57

-0.07±0.73

Absence

0.72±1.51

0.22±0.74

0.07±0.50

0.20±1.92

N = Number of patients who received ≥ 1 dose of investigational product and had a baseline and at least 1 post-baseline measurement of the radiograph score.

Data are mean ± SD.

RA=rheumatoid arthritis, CRP=C-reactive protein, ESR=erythrocyte sedimentation rate, RF=rheumatoid factor, Anti-CCP=anti-cyclic citrullinated peptide, SWJ=swollen joints

Conclusion

Denosumab significantly inhibited the progression of the bone erosion at 12 months in Japanese patients with RA. While some subgroups were small, denosumab also consistently inhibited the progression of the bone erosion in important subgroups. These results indicate that denosumab could inhibit the progression of bone destruction in RA patients with risk factors for radiographic damage.

Disclosure:

N. Ishiguro,

Daiichi Sankyo Company Ltd, Takeda Pharmaceutical Co Ltd, Hisamitsu Pharmaceutical Co Inc, Otsuka Pharmaceutical Co Ltd, Taisho Toyama Pharmaceutical Co Ltd, Kaken Pharmaceutical Co Ltd, Eisai Co Ltd, Janssen Pharmaceutical K.K, Bristol-Myers Squibb, Abbo,

5,

Takeda Pharmaceutical Co Ltd, Mitsubishi-Tanabe Pharmaceutical Co Ltd, Astellas Pharmaceutical Inc, Chugai Pharmaceutical Co Ltd, Abbott Japan, Bristol-Myers Squibb, Eisai Co Ltd, Daiichi Sankyo Company Ltd, Janssen, Kaken Pharmaceutical Co Ltd and Pfizer,

2;

Y. Tanaka,

Mitsubishi-Tanabe,

5,

Eisai,

5,

Chugai,

5,

Abbott Japan,

5,

Astellas,

5,

Daiichi-Sankyo,

5,

Abbvie,

5,

Janssen Pharmaceutica Product, L.P.,

5,

Pfizer Inc,

5,

Takeda,

5,

AstraZeneca,

5,

Eli Lilly Japan,

5,

GlaxoSmithKline,

5,

Quintiles,

5,

MSD,

5,

Asahi-Kasei,

5,

Bristol-Myers Squibb,

2,

Mitsubishi-Tanabe,

2,

Abbvie,

2,

Chugai,

2,

Astellas,

2,

Daiichi-Sankyo,

2;

H. Yamanaka,

AbbVie, Asahikasei Pharma, Astellas, Bristol-Myers-Squibb, Chugai, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, MSD, Nippon Kayaku, Pfizer, Santen, Taisho-Toyama, Takeda, Teijin Pharma,

2,

AbbVie, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Pfizer, Takeda, Teijin Pharma,

5;

T. Yoneda,

Daiichi-Sankyo,

5;

T. Ohira,

Daiichi-Sankyo,

3;

N. Okubo,

Daiichi-Sankyo,

3,

Daiichi-Sankyo,

1;

H. K. Genant,

Daiichi-Sankyo, Amgen, Lilly, Merck, Pfizer, Janssen, Novartis, Takeda, Servier, CCBR-SYNARC,

5;

D. van der Heijde,

AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi-Sankyo, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Vertex,

5,

Imaging Rheumatology bv,

3;

T. Takeuchi,

Abbott Japan Co., Ltd., Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Sanofi–Aventis K.K., Santen Pharmaceutica,

2,

Abbott Japan Co., Ltd., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Astellas Pharma, Diaichi Sankyo Co.,Ltd.,

8,

Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., Abbivie GK, Daiichi Sankyo Co.,Ltd.,

5.

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