Effects of Denosumab in Japanese Patients With Rheumatoid Arthritis Treated With Conventional Antirheumatic Drugs: 36-month Extension of a Phase III Study.

Abstract

OBJECTIVE:

To evaluate the safety and efficacy of long-term denosumab 60 mg every 6 months (Q6M) or every 3 months (Q3M) in patients with rheumatoid arthritis (RA).

METHODS:

This 12-month, randomized, double-blind, placebo-controlled, multicenter, phase III trial with an open-label extension period from 12 to 36 months (DESIRABLE) enrolled Japanese patients with RA treated with placebo (P) for 12 months followed by either denosumab Q6M (P/Q6M) or denosumab Q3M (P/Q3M) for 24 months; 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 score (mTSS), bone erosion score (BES), and joint space narrowing (JSN) score.

RESULTS:

Long-term treatment better maintained mTSS and BES suppression in the P/Q3M and Q3M/Q3M vs P/Q6M and Q6M/Q6M groups; changes from baseline in total mTSS (standard error) at 36 months were 2.8 (0.4) and 1.7 (0.3) vs 3.0 (0.4) and 2.4 (0.3), respectively, and corresponding changes in BES were 1.3 (0.2) and 0.4 (0.2) vs 1.4 (0.2) and 1.1 (0.2), respectively. No JSN effect was observed. Bone mineral density consistently increased in all groups after denosumab initiation, regardless of concomitant glucocorticoid administration. Serum C-terminal telopeptide of type I collagen decreased rapidly at 1 month postdenosumab administration (in both the initial 12-month [Q3M and Q6M groups] and long-term treatment [P/Q3M and 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 BES progression, higher dosing frequency at an earlier treatment stage may be needed to optimize treatment. Denosumab was generally well tolerated. (ClinicalTrials.gov: NCT01973569).

• Authors: Yoshiya Tanaka, Tsutomu Takeuchi, Satoshi Soen, Hisashi Yamanaka, Toshiyuki Yoneda, Sakae Tanaka, Takaya Nitta, Naoki Okubo, Harry K Genant, Désirée van der Heijde
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 48 Issue 11 Pg. 1663-1671 (Nov 2021) ISSN: 0315-162X [Print] Canada
• PMID: 33858976 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2021 by the Journal of Rheumatology.

Chemical References

• Antirheumatic Agents
• Bone Density Conservation Agents
• Denosumab

Topics

• Antirheumatic Agents (adverse effects)
• Arthritis, Rheumatoid (drug therapy)
• Bone Density
• Bone Density Conservation Agents (pharmacology, therapeutic use)
• Denosumab (adverse effects)
• Double-Blind Method
• Humans
• Japan
• Treatment Outcome