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Denosumab in erosive hand arthritis: Structure repair of interphalangeal joints seems possible

Presented by
Prof. Ruth Wittoek, Ghent University Hospital, Belgium
ACR 2022
Phase 2
Denosumab significantly led to remodelling and reduced progression in erosive hand osteoarthritis (OA). The treatment with twice the dose typically used in osteoporosis did not raise safety concerns.

Exploring new treatment options for erosive hand OA, a Belgian team of investigators conducted a phase 2 trial (NCT02771860) to test the receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor denosumab for its potential in this setting [1].

In this proof-of-concept study, 100 adult patients with radiographically proven erosive hand OA were randomised to denosumab 60 mg every 12 weeks or placebo. Eligible patients needed to have radiographic evidence of erosions or joint space loss as well as inflammatory signs of interphalangeal joints. The primary endpoint consisted of the change in the Ghent University Scoring System (GUSS) at week 24. “Positive changes indicate remodelling or repair, while negative changes show erosive progression,” Prof. Ruth Wittoek (Ghent University Hospital, Belgium) clarified. After 48 weeks in the placebo-controlled period, participants could decide to enter an open-label extension up to week 96.

The study population was predominantly female (around 80%), the mean age was 61 years, and the mean disease duration was 6 years. The average observed number of affected interphalangeal joints in both hands was just under 4. Regarding the primary endpoint, the mean change in GUSS was higher with denosumab compared with placebo (6.0 in the denosumab arm and -2.8 in the placebo arm; P=0.024). This shows that the treatment group exhibited signs of remodelling, while the erosion progressed in the placebo group. This difference grew until week 48: 10.1 (denosumab) versus -7.9 (placebo), resulting in a stronger level of evidence (P=0.003). “During the open-label extension, the denosumab-treated patients continued to increase to show remodelling, while the former placebo-treated group, now also receiving denosumab, showed new signs of remodelling, so no more erosive progression,” Prof. Wittoek further elaborated. Among the secondary endpoints, the development of new erosive joints at week 48 also reflected the superiority of denosumab over placebo: 1.8% compared with 7.0% (P<0.001). The decrease in pain and functional impairment was not significant in the trial's first phase. However, differences between those who started on denosumab and those who switched from placebo at week 48 were present at week 96 (P=0.028 for pain reduction and P=0.025 for functional impairment).

The safety profile showed 125 adverse events in the placebo arm and 98 in the denosumab group. Serious adverse events occurred in 7 participants in both groups and led to discontinuation in 3 cases each. Overall, no new safety concerns came to light on the double-dosing regimen.

“This is the first proof-of-concept study that suggests that structure modification is an achievable goal in patients with erosive hand OA. RANKL is a promising target in treating erosive hand OA,” Prof. Wittoek concluded.


    1. Wittoek R. Effect of denosumab on structure modification in erosive hand osteoarthritis: results of a 48-week, monocentric, randomised, placebo-controlled, double-blind phase 2 study and open label extension phase. L05, ACR Convergence 2022, 10–14 November, Philadelphia, USA.


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