乌鸦传媒

PHILADELPHIA -- The osteoporosis drug denosumab (Prolia) not only stopped structural progression in patients with erosive osteoarthritis of the hand, but showed signs of reversing the damage, according to findings from a small trial.

Patients receiving the drug during a had a mean increase of 10.1 points under the radiographic Ghent University Scoring System (GUSS) for joint erosion, indicating healthy remodeling, whereas mean scores declined 7.9 points in the placebo group, reported Ruth Wittoek, MD, of the University of Ghent in Belgium.

At the end of an open-label extension lasting another 48 weeks, in which all patients including those in the initial placebo group were given denosumab, the change from baseline in GUSS score reached 18.8 points for those originally assigned to the drug, and 17.0 among the former placebo participants, she reported in a presentation at the American College of Rheumatology (ACR) annual meeting.

But it was not all ponies and fudge sundaes for the study's 100 participants. Although the drug was clearly effective for radiographic outcomes, patient assessments of pain and functional impairment did not budge until the final evaluation at week 96, and then not by very much.

These results were indicative of osteoarthritis's complexity. Pain and functional disability do not correlate perfectly with structural damage, Wittoek said in response to an ACR attendee, and the long delay in seeing improvements in these patient-centered outcomes probably suggests that denosumab could never be a monotherapy for osteoarthritis. "Having to wait 2 years [for benefit in pain and function] is hard for our patients," she said.

Denosumab targets a molecule known as RANKL (receptor activator of nuclear factor kappa-B ligand), a cousin of tumor necrosis factor that plays an important role in bone dynamics. It's been available for many years to treat osteoporosis and (in a different formulation) to prevent bone-related adverse events (AEs) associated with certain cancers. Recent studies have implicated RANKL in the erosive effects of rheumatoid arthritis as well as osteoarthritis.

These considerations prompted Wittoek and colleagues to undertake the trial on their own initiative, approaching denosumab's manufacturer, Amgen, to provide the drug. They then enrolled patients and randomized them 1:1 to denosumab at 60 mg or placebo injected every 12 weeks. To be eligible, patients needed to have x-ray evidence of erosion in at least one hand joint as well as inflammatory signs (clinical or by ultrasound) in at least one joint.

Mean age for participants was about 61, and approximately 80% were women. Pain scores averaged 4.7 on a 10-point scale. Disability was scored using the 30-point Functional Index for Hand OsteoArthritis (FIHOA) system; the baseline mean was 10.4.

Besides change in GUSS score, the trial also assessed development of new erosive joints during treatment. In the denosumab group, the average was 1.8 at week 48, compared with 7.0 in the placebo group. After the switch to open-label denosumab in the extension phase, the result was a flat zero at week 96 in the original denosumab group and 0.7 for participants who had previously received placebo.

Mean pain scores, however, stayed stubbornly above 4.0 points at week 48 irrespective of treatment. They declined to 2.4 in the original denosumab group during the extension, and edged down to 3.5 for those switching from placebo. FIHOA scores increased slightly through week 48 (indicating more disability); at week 96, they averaged 8.5 points in the original denosumab group and 10.8 in the original placebo group.

AEs were as expected with denosumab treatment, Wittoek said.

She concluded that RANKL is "a promising target" in erosive hand osteoarthritis, with denosumab's relative safety and familiarity a plus. Whether the treatment can also restore damaged and lost cartilage awaits further analysis, she said.

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