Bone erosions in response to inflammation in RA are driven by osteoclasts which are in turn activated by RANKL (Receptor Activator for Nuclear Factor κ B Ligand) binding to its receptor RANK. Inhibition of RANKL has the potential to retard bone erosions in RA patients, thereby limiting progressive joint damage and destruction. Results of a randomized, double-blind, placebo controlled, Phase II clinical trial of denosumab, a monoclonal antibody inhibitor of RANKL have been published (Cohen et al. Arthritis Rheum 2008; 58(5): 1299). The design and result of the study have been presented here from presentations at the 2007 EULAR and ACR Annual Scientific meetings.
This new agent represents a new approach to the treatment of erosive inflammatory arthritis. On the surface, using a drug with no effect on articular inflammation may not sound viable. However, it is compelling to contemplate combination regimens with denosumab that may result in control of articular signs and symptoms with concomitant suppression of erosions with little risk of additional toxic side effects. It is interesting to note that joint space narrowing was not suppressed by denosumab, suggesting that the mechanisms of cartilage destruction and erosions are distinct in RA. The efficacy of denosumab to treat post-menopausal osteoporosis is a potential added benefit.
