Denosumab -- a monoclonal antibody that binds RANKL, which is necessary for osteoclast development -- inhibits structural damage in rheumatoid arthritis patients, according to a report in the May issue of Arthritis & Rheumatism.
"This patient research validates the basic research regarding the role of RANKL/RANK/OPG in osteoclast activation/recruitment and subsequent joint erosion," Dr. Stanley B. Cohen told Reuters Health. "If further studies confirm this observation, this will provide us another tool to prevent joint damage."
Dr. Cohen from Metroplex Clinical Research Center, Dallas, Texas and colleagues in the Denosumab Rheumatoid Arthritis Study Group evaluated the ability of denosumab versus placebo every 6 months to decrease the progression of structural damage in a phase II study of 218 patients with rheumatoid arthritis who were receiving methotrexate.
The MRI erosion score changed significantly less from baseline to 6 months in the denosumab groups than in the placebo group, the authors report.
Just under 40% of the placebo patients had stable or improved MRI erosion scores at 6 months, compared with 51% of patients who received denosumab 60 mg and 64% of patients who received denosumab 180 mg.
Erosion scores increased more in the placebo group than in the 60-mg and 180-mg denosumab groups at 6 and 12 months, the researchers note, but there was no evidence of an effect of denosumab on the joint space narrowing score.
Denosumab treatment was also associated with a sustained decrease in markers of bone turnover and an increase in bone mineral density, the investigators say.
Rates of adverse events were comparable among the treatment and placebo groups.
"The impact on erosions should be similar to TNF inhibitors, as TNF stimulates RANK ligand, which denosumab blocks." Dr. Cohen explained.
"From the discovery of this pathway in the late 1990s it was only a decade until proof of concept in patients," Dr. Cohen added. "This points out how rapidly basic discoveries are translating into potential for improved patient outcomes."
Arthritis Rheum 2008;58:1299-1309.