Session Information
Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
Background/Purpose:
RANKL is an essential factor for osteoclast differentiation and activation. Denosumab, a fully human monoclonal IgG2 antibody, is a potent inhibitor of RANKL and osteoclastgenesis. In this study, the pathological effect of denosumab was investigated with efficacy on bone turnover and structural damage in Japanese patients with RA receiving MTX.
Methods:
The 12-month, multicenter, randomized, double-blind, placebo-controlled, phase II study included 4 treatment groups; denosumab 60 mg every 6 mos (Q6M), 3 mos (Q3M), or 2 mos (Q2M) or placebo. Daily supplements of vitamin D (≥400 IU) and calcium (≥600 mg) were taken concomitantly in all groups. Bone mineral density (BMD) of the lumbar spine (L1 to L4) and total hip (including the femoral neck) were measured by dual energy X-ray absorptiometry at 0, 6 and 12 mos. Serum CTX-I and P1NP, and urinary CTX-II were collected at 0, 1, 2, 3, 4, 6 and 12 mos. Bisphosphonates treatment was prohibited throughout the study.
Results:
Of the 350 pts enrolled, 346 pts received treatment and 35 pts were discontinued; placebo n=6; Q6M, n=8; Q3M, n=13; and Q2M, n=8. Demographic and clinical characteristics were comparable between groups (Table 1).
Significant increases of BMD in lumbar spine and total hip at month 12 were demonstrated in the RA pts treated with denosumab, including the pts with concomitant glucocorticoid use (Table 2).
Markers of bone resorption and bone formation, CTX-I and P1NP, respectively, were decreased by denosumab treatment. These results correspond with significant increases in BMD and suppression of progression of RA in patients treated with denosumab for 12 mos. Denosumab treatment rapidly reduced CTX-II with sustained levels in a dose dependent manner (Figure 1).
Figure 1. Percent change from baseline for CTX-II/creatinine
Conclusion:
Significant increases in BMD were observed after 12-mo denosumab treatment in comparison to placebo in patients with RA regardless of glucocorticoid use. Denosumab inhibits the activation and survival of osteoclasts, which leads to the reduced bone turnover and reduction of bone resorption. Furthermore, suppression was evident in marker of cartilage metabolism, CTX-II, suggesting an effect of denosumab on cartilage turnover.
Disclosure:
Y. Tanaka,
Bristol-Myers, Mitsubishi Tanabe Pharma, AbbVie, MSD, Chugai Pharmaceutical, Astellas Pharma, Daiichi Sankyo,
2,
Mitsubishi Tanabe Pharma, Eisai, Chugai Pharmaceutical, Abott Japan, Astellas Pharma, Daiichi Sankyo, AbbVie, Janssen Pharmaceutical, Pfizer Japan, Takeda Pharmaceutical, Astra Zeneca, Eli Lilly Japan, GlaxoSmithKline, Quintiles, MSD, Asahi Kasei Pharma,
5;
T. Takeuchi,
Abott Japan, Astellas Pharma, Bristol-Myers, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Mitsubishi Tanabe Pharma, Pfizer, Sanofi-aventis, Santen Pharmaceutical., Takeda Pharmaceutical, Teijin Pharma, AbbVie, Asahi Kasei Pharma, Taisho Toyama Pharma,
2,
Abott Japan, Bristol-Myers, Chugai Pharmaceutical, Eisai, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical, Astellas Pharma, Daiichi Sankyo, Astra Zeneca, Eli-Lilly Japan, Novartis Pharma, Asahi Kasei Pharma, AbbVie,
5;
N. Ishiguro,
Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Astellas Pharma, Chugai Pharmaceutical, Abott Japan, Bristol-Myers, Eisai, Janssen Pharmaceutical, Kaken Pharmaceutical, Pfizer Japan, Taisho Toyama Pharmaceutical, Otsuka Pharmaceutical, Daiichi Sankyo,
5;
H. Yamanaka,
Abott Japan, Bristol-Myers, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Pfizer Japan,
5;
T. Yoneda,
Daiichi Sankyo,
5;
H. K. Genant,
Amgen, Bristol-Myers Squibb, Eli Lilly & Co., Genentech, GlaxoSmithKline, Merck & Co., Novartis Pharmaceuticals, Pfizer, Roche Pharmaceutical, ONO Pharma USA, Servier, and Synarc,
5;
D. van der Heijde,
AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Centocor Biotech, Chugai Pharmaceutical, Eli Lilly & Co., GlaxoSmithKline, Imaging Rheumatology, Merck & Co., Novartis Pharmaceuticals, Pfizer, Roche Pharmaceutical, Sanofi-Aventis, Schering-Ploug,
5.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/estimation-of-the-effect-of-denosumab-on-bone-loss-from-the-results-of-the-12-month-phase-ii-study-in-patients-with-rheumatoid-arthritis-ra-on-background-methotrexate-mtx/