Effect of Denosumab on Joint Destruction in Subgroups of Patients with Rheumatoid Arthritis

Periarticular bone erosions are a diagnostic feature of RA and are detected using radiographic imaging.1,6 They result from progressive periarticular osteoporosis resulting from an imbalance between bone resorption and inadequate bone formation at the joint margins.7 On imaging, they appear as breaks in the cortical bone accompanied by loss of subchondral trabecular bone and bone marrow edema.1,6 Although bone erosions occur in healthy people or patients with other joint diseases, they are more severe in patients with RA.6 Bone erosions arise early in the course of RA (within a few weeks to a few months of onset in some patients).1,7 They most often affect metacarpophalangeal joints and predict more severe disease.1,7 Approximately 63% of patients with RA have erosions at diagnosis.1 Seropositivity and smoking increase the risk for bone erosions.1 Evidence suggests DMARDs and the nuclear factor-kB ligand inhibitor denosumab can prevent progression of bone erosions, but no treatment appears to repair erosions.1,2,7
Year long treatment with denosumab reduced the progression of joint destruction in patients with rheumatoid arthritis.

Treatment with denosumab may reduce the progression of joint destruction in patients with rheumatoid arthritis (RA) with risk factors for radiographic damage, according to study results published in Rheumatic & Musculoskeletal Diseases.

There are data supporting the benefits of denosumab to reduce the progression of joint destruction in patients with RA. The aim of the current study was to evaluate the effect of denosumab on progressive joint destruction in Japanese patients with RA and in subgroups of patients using data from the 12-month, double-blind, placebo-controlled DRIVE (phase II) and DESIRABLE (phase III) studies.

Patients with RA were randomized to denosumab 60 mg every 6 months, every 3 months or placebo. The van der Heijde-modified total Sharp score (mTSS), the modified Sharp erosion score (ES) and the joint space narrowing score (JSNS) were assessed in all patients. The changes from baseline in all 3 measures at 12 months were assessed in the pooled analysis of all patients, and changes from baseline in mTSS were assessed in the subgroup analyses, which stratified patients by risk factors for radiographic damage.

A total of 909 patients were included in the pooled analysis, including 302 patients treated with denosumab every 6 months, 301 treated with denosumab every 3 months and 306 in the placebo group.

At 12 months, treatment with denosumab every 6 or every 3 months significantly reduced the progression of mTSS (mean scores, 0.88, P = .0024 and 0.66, P = .0002), compared with placebo (mean score, 1.50), mainly due to ES reduction (mean scores, 0.44, P = .0006 and 0.20, P < .0001; compared with 0.98). However, denosumab had no effect on JSNS vs placebo in either treatment arm.

In the interaction analyses, researchers identified a significant interaction between anti-cyclic citrullinated peptide (CCP) antibodies, glucocorticoid use and baseline ES.

The changes in mTSS were significantly greater in patients with anti-CCP antibody-positive status, compared with those who were negative for the antibody. In the anti-CCP antibody-positive group, denosumab every 6 or every 3 months reduced progression of mTSS compared with placebo (mean 1.15, P = .0008 and 0.89, P < .0001 vs. 2.10, respectively). However, in patients with anti-CCP antibody-negative status,

there were almost no changes in mTSS in any groups, including the placebo group.

Significant reductions in progression of mTSS were seen in both denosumab dose groups than placebo, regardless of glucocorticoid use or baseline ES.

The study had several limitations, including the relatively small sample size in some subgroups, relatively short-term treatment, and inclusion of patients who had partially controlled disease activity.

“These results indicate that denosumab broadly reduces the progression of joint destruction in RA patients with risk factors for radiographic damage but is especially effective in patients who are anti-CCP antibody positive,” concluded the researchers.


Tanaka Y, Soen S, Ishiguro N, et al. Identifying the preferable rheumatoid arthritis subgroups for intervention with the anti-RANKL antibody denosumab to reduce progression of joint destruction. RMD Open. 2020;6(2):e001249. doi:10.1136/rmdopen-2020-001249