Denosumab achieved partial repair of erosions in patients with rheumatoid arthritis taking disease-modifying antirheumatic drugs, while erosion continued to progress in patients receiving alendronate, according to recent findings.
The study was a post hoc analysis of a single-center, open-label, randomized controlled trial (RCT) evaluating the efficacy of denosumab and alendronate on changes in volumetric bone mineral density (BMD) and microstructure in RA patients. The researchers enrolled 40 consecutive, ambulatory Chinese female patients seen at the rheumatology clinic of the Prince of Wales Hospital in Hong Kong. Eligible participants met the following requirements: RA based on the ACR/EULAR criteria, age 18 years or older, lumbar spine or total hip or distal radius T score less than 21 by dual x-ray absorptiometry, and no severe deformities in metacarpophalangeal joints that would affect longitudinal evaluation by HR-pQCT.
Researchers randomly assigned the 40 patients into groups undergoing treatment with either subcutaneous injection of denosumab 60 mg once (n = 20) or oral alendronate 70 mg weekly (n = 20). Baseline disease-modifying antirheumatic drug (DMARD) treatments were continued in all patients, with the dose of DMARDS adjusted as needed within approved doses. Glucocorticoids and/or NSAIDS were permitted at any point in the study.
Investigators evaluated patients at baseline, month 3, and month 6 by the same senior rheumatologist. At each visit, the clinician assessed 28 joints for tenderness and swelling, and measured C-reactive protein (CRP) levels. The Disease Activity Score in 28 joints (DAS28)-CRP level score was used to evaluate disease activity.
HR-pQCT was used to evaluate bone erosions in the second metacarpal head of the nondominant hand. Researchers documented the presence, number, and location of erosions at baseline, 3 months, and 6 months. The researchers also recorded the maximum depth of each erosion, erosion volume, and erosion depth. Also documented at baseline, 3 months and 6 months was the presence and degree of marginalized osteoporosis in the second metacarpal head of the nondominant hand.
Investigators identified 42 erosions at baseline. They found no significant baseline difference between the two groups in the mean width, depth and volume of bone erosions (P = .05 for all). At 3 months, researchers observed no significant change in erosion size in either group (P = .05). At 6 months, a significant reduction was seen in erosion width, depth and volume in the denosumab group (–0.23 mm, width reduction; –0.16 mm, depth reduction; all P < .01). However, these measures significantly increased in the alendronate group (0.19 mm, width increase; 0.32 mm depth increase, and 1.38 mm3 volume increase; all P < .01). The between-group differences in these measures were statistically significant between the groups at 6-month follow-up (all P = .01).
At baseline, the mean BMD of the margin around the erosion was comparable between both groups. At 6 months, quantitative analysis revealed a significant increase in mean marginal BMD only in patients treated with denosumab (19.75 mg/cm3; P < .05 for denosumab and –5.44 mg/cm3; P = .51 for alendronate; P < .05 for between-group differences).
“Inhibition of receptor activator of NF-kB ligand by denosumab can induce partial repair of erosions in patients with RA, while erosions continued to progress in patients treated with alendronate,” the researchers wrote. “This study provides important evidence that denosumab represents a new and safe treatment strategy that not only protects against bone-destructive aspects of the disease, but also increases the probability of healing of pre-existing erosions.” – by Jennifer Byrne
Disclosure: The researchers report no relevant disclosures.