Progression of Bone Erosion Slows With Addition of Denosumab to DMARDs in RA

The addition of denosumab to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) may inhibit the progression of bone erosion and improve bone microarchitecture in patients with rheumatoid arthritis (RA), according to study findings published in Arthritis Research & Therapy.

Researchers in Japan conducted an open-label randomized parallel-group study among patients with RA to explore the difference in bone erosion inhibition between csDMARD therapy plus denosumab vs csDMARD therapy alone.

Patients who were randomly assigned to csDMARD plus denosumab group received 60 mg of subcutaneous injections every 6 months for 12 months, and those in the csDMARD only group continued their treatment for 12 months.

Researchers measured bone microarchitecture and other bone-related parameters, such as depth, volume, and width of bone erosion, using high-resolution peripheral quantitative computed tomography (HR-pQCT), at baseline and at 6 and 12 months after initiating therapy. The researchers also compared treatment-related adverse events between the 2 groups.

The primary endpoint was the change in depth of bone erosion in the second and third metacarpal heads after 6 months of therapy, as measured by HR-pQCT.

After 6 months of therapy, patients in the csDMARD plus denosumab vs csDMARD only group demonstrated reduced changes in the depth of bone erosion in the second and third metacarpal heads (-0.57 mm vs -0.22 mm; difference in change between groups, -0.35 mm; P =.2716). Width and volume of bone erosion changed by -0.20 mm (P =.4953) and -4.41 mm³ (P =.4379), respectively.

Between baseline and 12 months, bone erosion changes in depth, width, and volume differed between the 2 groups by -0.35 mm (P =.2251), -0.24 mm (P =.4364), and -3.07 mm³ (P =.5979), respectively.

The addition of denosumab to csDMARD therapy inhibited bone biomarkers in patients with RA, resulting in significant improvements to the bone microarchitecture. The researchers noted that denosumab did not effectively suppress matrix metalloproteinase-3, an enzyme that contributes to cartilage destruction, which may indicate that denosumab selectively suppressed bone destruction instead of cartilage destruction in RA.

Treatment-related adverse events occurred at similar rates in both the csDMARD plus denosumab and the csDMARD only groups (52.2% vs 56.5%). Serious adverse events also occurred at similar rates in both groups (4.3% vs 8.7%).

Study limitations included the relatively short observation period, the heterogeneity of the study population (some of whom already had osteoporosis), lack of smoking history assessment, and the restriction of bone erosions to the second and third metacarpal heads, leading to a much smaller sample size with positive bone erosion at these sites..

“Although the addition of denosumab to conventional treatment did not lead to a statistically significant improvement in bone erosion, numerical improvements in these parameters suggest that the addition of denosumab to csDMARDs may inhibit the progression of bone erosion,” the study authors said. “The results also showed improvements in bone micro-architecture parameters, which suggest the benefit of adding denosumab to conventional treatment for improving bone micro-architecture.”

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.

This article originally appeared on Rheumatology Advisor