Denosumab slows progression of erosive osteoarthritis of hand

A new study conducted by Ruth Wittoek and team showed that denosumab clearly modifies the structure of erosive hand osteoarthritis (OA), resulting in considerably slower erosive development after 24 weeks of therapy and a stronger therapeutic impact after 48 weeks.

The findings of this study were presented in American College of Rheumatology Convergence 2022.

Osteoarthritis of the hands that is erosive has few effective treatments. The Receptor Activator of Nuclear Factor kappa-b Ligand inhibitor denosumab impacts osteoclast activity and bone resorption. This clinical trial's objectives were to investigate the therapeutic advantages and safety of subcutaneous denosumab 60 mg every three months versus placebo in patients with erosive hand OA and to investigate the structure-modifying impact of denosumab in those individuals.

In a monocentric clinical study spanning 48 weeks, 100 patients with erosive hand OA were randomized to receive denosumab or a placebo. Thereafter, an open-label extension phase continued through week 96. The change in the overall Ghent University Scoring System (GUSSTM) score at week 24 served as the main radiographic objective. GUSSTM (0-300) is a semi-quantitative scoring system that was created expressly to incorporate scoring of both erosive progression (reduction in score) and evidence of repair (increase in score) in radiographic changes in erosive hand OA and is capable of detecting changes over the short term. The percentage of new erosive joints at week 48 served as the secondary goal. Clinical results and exploratory imaging (ultrasound) were evaluated. After receiving treatments for 96 weeks, radiographic and clinical improvements were assessed. Bone mineral density alterations by dual-energy X-ray absorptiometry, laboratory changes, and (severe) adverse events were all documented as safety results. Intent-to-treat analyses of primary efficacy were carried out. Generalized estimating equations were used to analyze changes in GUSSTM at the joint level while taking within-patient clustering into account.

The key findings of this study were:

1. Denosumab and a placebo were administered subcutaneously to 51 and 49 individuals, respectively.

2. At week 24, it was discovered that denosumab had a statistically significant larger total change GUSSTM than placebo.

3. At week 48, this discrepancy became even further. At week 48, denosumab substantially reduced the development of new erosive joints (1.8%) compared to placebo (7.0%).

4. Both groups maintained remodeling following open-label therapy until week 96, and both pain and function considerably improved from baseline.

5. There was no difference in the frequency of negative occurrences between the two groups.

Reference:

Wittoek R, Verbruggen A, Vanhaverbeke T, Elewaut D. 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 [abstract]. In American College of Rheumatology. ACR Convergence 2022. Arthritis Rheumatol; 74 (suppl 9). November 14, 2022.