Yoshiya Tanaka1, Tsutomu Takeuchi1, Satoshi Soen1, Hisashi Yamanaka1, Toshiyuki Yoneda1, Sakae Tanaka1, Takaya Nitta1, Naoki Okubo1, Harry K Genant1, Désirée van der Heijde1. 1. First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; Department of Orthopedics and Rheumatology, Kindai University Nara Hospital, Ikoma, Japan; Director of Rheumatology, Sanno Medical Center, Tokyo, Japan; Department of Biochemistry, Osaka University Graduate School of Dentistry, Osaka, Japan; Orthopedic Surgery and Spinal Surgery, The University of Tokyo, Tokyo, Japan; Daiichi Sankyo Co., Ltd, Japan; Departments of Radiology, Medicine and Orthopedic Surgery, University of California, California, USA; Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. This study was funded by Daiichi Sankyo Co., Ltd. Address correspondence to Yoshiya Tanaka First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan. E-mail: tanaka@med.uoeh-u.ac.jp.
Abstract
OBJECTIVE: To evaluate safety and efficacy of long-term denosumab 60 mg every 6 (Q6M) or 3 months (Q3M) in rheumatoid arthritis (RA) patients. METHODS: This 12-month, randomised, double-blind, placebo-controlled, multicentre phase 3 trial with an open-label extension period from 12 to 36 months (DESIRABLE) enrolled Japanese RA patients treated withplacebo for 12 months then denosumab Q6M (P/Q6M) or denosumab Q3M (P/Q3M); denosumab Q6M for 36 months (Q6M/Q6M); or denosumab Q3M for 36 months (Q3M/Q3M). Efficacy was assessed by van der Heijde modified total Sharp (mTSS), bone erosion (ES), and joint space narrowing (JSN) scores. RESULTS: Long-term treatment better maintained mTSS and ES suppression in the P/Q3M and Q3M/Q3M versus P/Q6M and Q6M/Q6M groups; changes from baseline in total mTSS at 36 months were 2.8 (standard error 0.4), 1.7 (0.3), 3.0 (0.4), and 2.4 (0.3), respectively; corresponding changes in ES were 1.3 (0.2), 0.4 (0.2), 1.4 (0.2), and 1.1 (0.2). No JSN effect was observed. Bone mineral density consistently increased in all groups after denosumab initiation, regardless of concomitant glucocorticoid administration. Serum C-telopeptide of type I collagen decreased rapidly at 1-month post-denosumab administration (both in the initial 12- month [Q3M, Q6M groups] and long-term treatment [P/Q3M, P/Q6M groups] phases). Adverse event incidence leading to study drug discontinuation was similar across treatment groups. CONCLUSION:Denosumab treatment maintained inhibition of progression of joint destruction up to 36 months. Based on effects on ES progression, higher dosing frequency at an earlier treatment stage may be needed to optimise treatment. Denosumab was generally well tolerated.
RCT Entities:
OBJECTIVE: To evaluate safety and efficacy of long-term denosumab 60 mg every 6 (Q6M) or 3 months (Q3M) in rheumatoid arthritis (RA) patients. METHODS: This 12-month, randomised, double-blind, placebo-controlled, multicentre phase 3 trial with an open-label extension period from 12 to 36 months (DESIRABLE) enrolled Japanese RApatients treated with placebo for 12 months then denosumabQ6M (P/Q6M) or denosumab Q3M (P/Q3M); denosumabQ6M for 36 months (Q6M/Q6M); or denosumab Q3M for 36 months (Q3M/Q3M). Efficacy was assessed by van der Heijde modified total Sharp (mTSS), bone erosion (ES), and joint space narrowing (JSN) scores. RESULTS: Long-term treatment better maintained mTSS and ES suppression in the P/Q3M and Q3M/Q3M versus P/Q6M and Q6M/Q6M groups; changes from baseline in total mTSS at 36 months were 2.8 (standard error 0.4), 1.7 (0.3), 3.0 (0.4), and 2.4 (0.3), respectively; corresponding changes in ES were 1.3 (0.2), 0.4 (0.2), 1.4 (0.2), and 1.1 (0.2). No JSN effect was observed. Bone mineral density consistently increased in all groups after denosumab initiation, regardless of concomitant glucocorticoid administration. Serum C-telopeptide of type I collagen decreased rapidly at 1-month post-denosumab administration (both in the initial 12- month [Q3M, Q6M groups] and long-term treatment [P/Q3M, P/Q6M groups] phases). Adverse event incidence leading to study drug discontinuation was similar across treatment groups. CONCLUSION:Denosumab treatment maintained inhibition of progression of joint destruction up to 36 months. Based on effects on ES progression, higher dosing frequency at an earlier treatment stage may be needed to optimise treatment. Denosumab was generally well tolerated.
Authors: Bernardo D'Onofrio; Michele di Lernia; Ludovico De Stefano; Serena Bugatti; Carlomaurizio Montecucco; Laura Bogliolo Journal: J Clin Med Date: 2022-04-22 Impact factor: 4.964