2022 ACR Blockbuster: Denosumab Can Significantly Delay the Progression of Erosive Hand Osteoarthritis!

Background and purpose: Erosive osteoarthritis consists of a large class of arthritic diseases, all of which are accompanied by a certain degree of inflammation, synovial hyperplasia (angiogenesis), which is involved in the course of osteolytic changes in or around the joints, known as erosion, especially the small joints
of the hands and feet.
Erosive hand osteoarthritis (OA) is a disabling condition
with limited treatments.
Nuclear factor kappa-B ligand inhibitor receptor activator denosumab can affect bone resorption and osteoclast activity
.
The purpose of this clinical trial is to investigate the structural modification effect of denosumab in patients with erosive hand osteoarthritis and to explore the clinical efficacy and safety
of subcutaneous injection of denosumab 60 mg/3 months versus placebo.

Methods: In a single-center clinical trial lasting 48 weeks, 100 patients with erosive hand osteoarthritis were randomly assigned to placebo or denosumab, followed by an open-label extension to week 96
.
The primary imaging endpoint was change
in overall GUSS™ score at week 24.
GUSS™ (0-300) is a specially developed semi-quantitative scoring system that combines the scoring of two aspects of erosive hand-oa radiographic changes, namely erosive progression (decreased score) and signs of repair (increased score) (1), and is able to detect short-term changes (2).

The secondary endpoint was the percentage of
newly eroded joints at week 48.
To assess exploratory imaging (ultrasound) and clinical outcomes (pain, number of tender joints, number of swollen joints, grip strength, Australian-Canadian hand osteoarthritis index, and hand osteoarthritis function index).

Imaging and clinical changes
were measured after 96 weeks of treatment.
Safety outcomes including (serious) adverse events, laboratory changes, and changes in bone density by dual-energy radiogram densitometry were
recorded.
Initial efficacy analysis
was performed using intention-to-treat therapy.
Changes in GUSS™ were analyzed at the joint level using generalized estimation equations, using robust standard errors
.

Results: Denosumab was injected subcutaneously in 51 patients and placebo was injected subcutaneously in 49 patients
.
At week 24, the total change in GUSS was statistically higher in the denosumab group compared with placebo (mean GUSS™™ change = 8.
9 (95% CI: 1.
0 to 16.
9; p = 0.
024)) (Figure 1).

This difference increased further at week 48 (ΔGUSS™ = 14.
3 (95% CI: 4.
6 to 24.
0; P = 0.
003))
。 At 48 weeks, the incidence of neoerosive joint studies (1.
8%) was significantly lower in the denosumab group than in the placebo group (7.
0%) (OR = 0.
23 (95% CI: 0.
10 to 0.
50); p < 0.
001) (Figure 2).

After open-label treatment until week 96, both groups continued to rebuild, and pain and function improved significantly from baseline
.
There was no difference
in the incidence of adverse events between groups.

Figure 1: Radiographic changes in GUSS^TM, the primary endpoint of the 48-week placebo control period and the extension to 96 weeks

Fig.
2 Radiographic changes in 48-week placebo-controlled period and extension to 96-week duration, by percentage of newly eroded joints (secondary endpoint)

Conclusion: Compared with placebo, Denosumab has obvious structural modification effect on erosive hand osteoarthritis, and erosion progression is significantly reduced after 24 weeks of treatment, and the treatment effect is enhanced
after 48 weeks.
Symptomatic improvement
was observed after continued treatment.

Ruth Wittoek, August Verbruggen, Tine Vanhaverbeke, et al.
Effect of Denosumab on Structure Modification in Erosive Hand Osteoarthritis: Results of a 48-Week, Monocentric, Randomized, Placebo-controlled, Double-blind Phase 2 Study and Open Label Extension Phase.
ACR Convergence 2022.
October 18, 2022.