TY - JOUR
T1 - Efficacy of denosumab with regard to bone destruction in prognostic subgroups of Japanese rheumatoid arthritis patients from the phase II DRIVE study
AU - Ishiguro, Naoki
AU - Tanaka, Yoshiya
AU - Yamanaka, Hisashi
AU - Yoneda, Toshiyuki
AU - Ohira, Takeshi
AU - Okubo, Naoki
AU - Genant, Harry K.
AU - Van Der Heijde, Désirée
AU - Takeuchi, Tsutomu
N1 - Funding Information:
Funding: This work was supported by Daiichi-Sankyo Co., Ltd. The sponsor was involved in the study conception, design, conduct, data collection and data analyses.
Funding Information:
Disclosure statement: T.O. and N.O. are employees of Daiichi Sankyo. N.I. has received research grants from Abbott, Astellas, Bristol-Myers-Squibb, Chugai and Daiichi Sankyo and has served on speakers’ bureaus for Hisamitsu, Janssen, Kaken, Mitsubishi Tanabe, Taisho Toyama and UCB. Y.T. has received research grants from AbbVie, Astellas, Chugai, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, Kyowa Hakko Kirin, Mitsubishi Tanabe, MSD, Ono, Pfizer and Takeda, and has received personal fees from Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer, Sanofi, UCB and YL Biologics. H.Y. has received research grants from AbbVie, Astellas, AYUMI, BMS, Chugai, Daiichi Sankyo, Eisai, Kaken, Mitsubishi Tanabe, MSD, Nippon Shinyaku Ono, Pfizer, Takeda, Teijin, Torii and UCB, and has received consulting fees from Astellas, BMS, Chugai, Daiichi Sankyo, Mitsubishi Tanabe, Nippon Kayaku, Pfizer, Takeda, Teijin and YL Biologics. T.Y. has received Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT #17H04377) and has received consulting fees from Daiichi Sankyo. H.K.G. has received consulting fees from Amgen, Agnovos, Bioclinica, Biomarin, Clementia, Daiichi Sanyo, Eli Lilly, Janssen, Medimmune, Merck, Novartis, Pfizer, Regeneron, Servier and Takeda. D.v.d.H. has received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB, and is the director of Imaging Rheumatology BV. T.T. has received research grants from AbbVie, Asahi Kasei, Astellas, AYUMI, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer and Takeda, and has received personal fees from AbbVie, Astellas, Astra Zeneca, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer, Sanofi, Taiho, Taisho Toyama, Takeda, Teijin and UCB.
Publisher Copyright:
© The Author(s) 2019.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Objectives. To evaluate the efficacy of denosumab for progressive bone erosion in risk factor subgroups of Japanese RA patients. Methods. This study included 340 RA patients on MTX from the dose-response study of Denosumab in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE study-a 12-month, multicentre, randomized, double-blind, placebo-controlled, phase II study). The patients were randomized to receive placebo or denosumab 60 mg every 6 months, 3 months or 2 months. Subgroup analyses involved baseline RF, ACPA, swollen joint count, CRP level, RA duration, ESR and glucocorticoid use. Results. Patients with risk factor positivity generally showed consistent results for the primary endpoint of the change in the modified Sharp erosion score at 12 months from baseline. In the placebo, every 6 months, every 3 months and every 2 months groups, the mean changes in the erosion score, according to the RF status (RF-positive vs -negative subgroups), were 1.18 vs 0.59, 0.25 (P = 0.0601 vs placebo) vs 0.31 (P = 0.0827), 0.21 (P = 0.0422) vs 0.02 (P = 0.0631) and 0.15 (P = 0.0010) vs 0.05 (P = 0.0332), respectively, while the mean changes in the erosion score, according to the ACPA status (ACPA-positive vs -negative subgroups), were 1.30 vs 0.07, 0.26 (P = 0.0142) vs 0.33 (P = 0.2748), 0.16 (P = 0.0058) vs 0.08 (P = 0.7166) and 0.09 (P < 0.0001) vs 0.08 (P = 0.8939), respectively. Conclusion. Denosumab is a potentially useful treatment option for RA patients who are positive for RF, ACPA and other possible risk factors. Trial registration.
AB - Objectives. To evaluate the efficacy of denosumab for progressive bone erosion in risk factor subgroups of Japanese RA patients. Methods. This study included 340 RA patients on MTX from the dose-response study of Denosumab in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE study-a 12-month, multicentre, randomized, double-blind, placebo-controlled, phase II study). The patients were randomized to receive placebo or denosumab 60 mg every 6 months, 3 months or 2 months. Subgroup analyses involved baseline RF, ACPA, swollen joint count, CRP level, RA duration, ESR and glucocorticoid use. Results. Patients with risk factor positivity generally showed consistent results for the primary endpoint of the change in the modified Sharp erosion score at 12 months from baseline. In the placebo, every 6 months, every 3 months and every 2 months groups, the mean changes in the erosion score, according to the RF status (RF-positive vs -negative subgroups), were 1.18 vs 0.59, 0.25 (P = 0.0601 vs placebo) vs 0.31 (P = 0.0827), 0.21 (P = 0.0422) vs 0.02 (P = 0.0631) and 0.15 (P = 0.0010) vs 0.05 (P = 0.0332), respectively, while the mean changes in the erosion score, according to the ACPA status (ACPA-positive vs -negative subgroups), were 1.30 vs 0.07, 0.26 (P = 0.0142) vs 0.33 (P = 0.2748), 0.16 (P = 0.0058) vs 0.08 (P = 0.7166) and 0.09 (P < 0.0001) vs 0.08 (P = 0.8939), respectively. Conclusion. Denosumab is a potentially useful treatment option for RA patients who are positive for RF, ACPA and other possible risk factors. Trial registration.
KW - Anti-cyclic citrullinated peptide antibody
KW - Bone erosion
KW - Denosumab
KW - Rheumatoid arthritis
KW - Rheumatoid factor
KW - Subgroup analysis
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U2 - 10.1093/rheumatology/key416
DO - 10.1093/rheumatology/key416
M3 - Article
C2 - 30602032
AN - SCOPUS:85066492621
VL - 58
SP - 997
EP - 1005
JO - Rheumatology and Rehabilitation
JF - Rheumatology and Rehabilitation
SN - 1462-0324
IS - 6
ER -