EFFECT OF DENOSUMAB ON STRUCTURE MODIFICATION IN EROSIVE HAND OSTEOARTHRITIS: RESULTS OF A 48-WEEKS, MONOCENTRIC, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND PHASE 2 STUDY AND OPEN LABEL EXTENSION PHASE
Authors: Wittoek R et al.
Erosive hand osteoarthritis (OA) is a disabling disease with limited therapeutic options. Denosumab, a Receptor Activator of Nuclear Factor kappa-β Ligand inhibitor affects bone resorption and osteoclast activity.
The purpose of this clinical trial was to study the structure modifying effect of denosumab in patients with erosive hand OA, and to explore the clinical benefits and safety of subcutaneous denosumab 60 mg every 3 months versus placebo.
One hundred patients with erosive hand OA were randomly allocated to placebo or denosumab in a monocentric clinical trial for 48 weeks, followed by an open-label extension phase through week 96. The primary radiographic endpoint was change in total Ghent University Scoring System (GUSS) at week 24. GUSS (0-300) is a semi-quantitative scoring system specifically developed to combine scoring of both aspects of radiographic changes in erosive hand OA, being erosive progression (decrease of score) and signs of repair (increase of score).
The secondary endpoint was the percentage of new erosive joints at week 48. Exploratory clinical outcomes (e.g., pain, tender joint count, swollen joint count, grip strength, the Australian-Canadian Hand Osteoarthritis Index and the Functional Index for Hand Osteoarthritis) were assessed. Radiographic and clinical changes after 96 weeks of treatments were measured.
51 and 49 patients received subcutaneous administration of denosumab or placebo, respectively. Total change GUSS was found statistically higher in denosumab compared to placebo at week 24 (mean change GUSS = 8.9). This difference further increased at week 48 (ΔGUSS = 14.3). Development of new erosive joints was significantly lower in denosumab (1.8%) compared to placebo (7.0%) at week 48. After open-label treatment through week 96, both groups continued remodeling and both pain and function significantly improved compared to baseline. Equal numbers of adverse events occurred in both groups.
This study demonstrates a significant structure and symptom modifying effect of Denosumab compared to placebo in patients with symptomatic erosive hand osteoarthritis: significantly less erosive progression occurs after 24 weeks treatment, and the treatment effect enhances after 48 weeks.
Thus, Denosumab could be a treatment option in patients with erosive hand osteoarthritis, especially in women with concomitant osteoporosis.