Anti-CCP positivity associated with denosumab response in RA patients
medwireNews: Denosumab may reduce the risk for mTSS worsening among patients with rheumatoid arthritis (RA) who have risk factors for radiographic progression, particularly those with anti-cyclic citrullinated peptide (CCP) antibody positivity, researchers report.
“Denosumab, a fully human monoclonal antibody […] that inhibits bone resorption by inhibiting RANKL, has been proven to prevent the progression of joint destruction, although it has no effect on cartilage and does not improve RA disease activity,” explain Yoshiya Tanaka (University of Occupational and Environmental Health, Kitakyushu, Japan) and co-researchers.
They add that “identifying the patient subpopulation in which denosumab is most effective is important in the clinical setting.”
The team conducted a pooled analysis of the phase 2 DRIVE and phase 3 DESIRABLE trials, including a total of 909 RA patients, aged an average of approximately 57 years, with a median disease duration of around 2 years.
As reported in RMD Open, the 302 patients receiving denosumab 60 mg every 6 months and the 301 receiving denosumab 60 mg every 3 months experienced significantly less worsening of mTSS over 1 year than the 306 patients given placebo, with average increases of 0.88 and 0.66 versus 1.50 points, respectively. There was a similar pattern of results for bone erosion score (ES), but denosumab did not affect joint space narrowing score in either treatment arm.
In their subgroup analysis, Tanaka and team found that “most subgroups with specific baseline disease activity markers associated with bone erosion progression showed consistent efficacy of denosumab with respect to mTSS and ES,” but “there were differences among subgroups depending on the presence or absence of some prognostic baseline factors.”
The greatest difference in denosumab efficacy was seen between patients who did and did not have anti-CCP antibodies. In the anti-CCP-positive group, the average change in mTSS was significantly smaller in patients treated with denosumab every 6 months or every 3 months relative to placebo (1.15 and 0.89 vs 2.10 points), but there were no significant between-group differences in the anti-CCP-negative group.
The investigators also report a significant interaction between baseline ES or glucocorticoid use and denosumab efficacy, but they say that “[c]hanges in mTSS versus placebo were observed in all denosumab dose groups, regardless of glucocorticoid use and baseline ES.”
And they conclude that “in future clinical practice, RA patients who are anti-CCP antibody positive may be the best candidates for denosumab treatment.”
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