Denosumab achieves structural modification in erosive hand osteoarthritis
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PHILADELPHIA — Denosumab successfully induces structural modifications patients with active erosive hand osteoarthritis, according to data presented at ACR Convergence 2022.
“Hand osteoarthritis is a prevalent and mainly female disease,” Ruth Wittoek, MD, PhD, of the department of rheumatology at Ghent University Hospital, in Belgium, told attendees. “The erosive subtype has some specific disease characteristics. The patients experience a high clinical burden of disease.”
Wittoek added that patients with hand OA experience higher levels of pain and functional impairment than individuals with rheumatoid arthritis or psoriatic arthritis.
“There is a huge unmet need for these patients with erosive hand osteoarthritis,” she said.
The researchers investigated the use of denosumab (Prolia, Amgen), a receptor activator of nuclear factor kappa-b (RANK) ligand inhibitor, regarding structure modifying effects in a cohort of 100 patients. The drug was administered at a dose of 60 mg for 3 months and compared with placebo.
The initial placebo-controlled arm lasted 48 weeks, while an open-label extension period, with all patients treated with active therapy, lasted through 96 weeks. There were 51 patients in the initial active therapy arm and 49 patients assigned placebo.
The mean patient age was approximately 60 years, and the population was female and “slightly overweight,” with pain scores averaging approximately five out of 10, according to Wittoek. The average number of impacted joints in the hand was almost four.
“This is a fairly representative hand OA population,” Wittoek said.
Change in total Ghent University Scoring System at week 24 served as the primary endpoint. The scoring system assesses for erosive progression and indicators of repair. The researchers also examined safety endpoints.
“We believe that the goal of treatment in hand osteoarthritis should be more ambitious than only symptom modification and should go for structural modification,” she said. “So, therefore, we chose a radiographic endpoint as the primary endpoint at week 24.”
According to Wittoek, denosumab bested placebo in terms of total change in the Ghent University Scoring System at 24 weeks, with a difference of 8.9 points (P = .024). By week 48, the difference in change between denosumab and placebo was 14.3 points (P = .003).
Denosumab was also associated with a significantly lower number of new erosive joints than placebo — 1.8% vs. 7% (OR = 0.23; P < .001).
“As you can see, at week 24, the denosumab group showed positive changes indicating remodeling,” Wittoek said. “The placebo group showed negative changes, showing further erosive progression.”
At week 48, the remodeling in the denosumab group, and the erosion in the placebo group, each increased (HR for new erosive joints = 0.23; P < .001).
“The level of significance, of course, was stronger,” Wittoek said.
After open-label treatment with denosumab through week 96, both groups continued remodeling, while pain and function significantly improved compared to baseline, according to Wittoek.
Regarding safety, there were a total of 98 events in the denosumab group, compared with 125 among patients who received placebo. There were seven serious events and three events that led to discontinuation in both groups.
“We see no new safety concerns than what is known for denosumab in osteoporosis,” Wittoek said.
“This is the first proof-of-concept study to show that structural modification is an achievable goal in patients with erosive hand osteoarthritis,” she added. “This suggests that RANK ligand is a promising target in treating erosive hand osteoarthritis.”
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Wittoek R. Abstract L05. Presented at: ACR Convergence 2022; Nov. 11-14, 2022; Philadelphia (hybrid meeting).
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