Denosumab inhibits joint destruction up to 3 years

Treatment with denosumab prevents the progression of joint destruction up to 36 months, results of a Japan study have shown. Higher dosing frequency at an earlier treatment stage may help optimize treatment, based on effects on bone erosion score (BES) progression.

This 12-month, randomized, double-blind, placebo-controlled, multicenter, phase III trial with an open-label extension period from 12 to 36 months evaluated 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).

Participants were treated with placebo for 12 months, followed by either denosumab Q6M or Q3M for 24 months (P/Q6M); with denosumab Q6M for 36 months (Q6M/Q6M); or with denosumab Q3M for 36 months (Q3M/Q3M). The investigators assessed efficacy using the van der Heijde modified total Sharp score (mTSS), BES, and joint space narrowing score.

Long-term treatment retained mTSS and BES suppression better in the P/Q3M and Q3M/Q3M than in the P/Q6M and Q6M/Q6M groups. Changes in total mTSS at 36 months from baseline were 2.8 and 1.7 vs 3.0 and 2.4, respectively, while corresponding changes in BES were 1.3 and 0.4 vs 1.4 and 1.1. No joint space narrowing effect was seen.

Bone mineral density consistently increased in all groups following denosumab initiation, regardless of concomitant glucocorticoid administration. Serum C-terminal telopeptide of type 1 collagen dropped quickly at 1 month after denosumab administration (in both the initial 12-month and long-term phases).

Of note, denosumab was well tolerated. Incidence of adverse events leading to treatment discontinuation was comparable across study groups.