Study validates the superiority of denosumab over bisphosphonates in managing rheumatoid arthritis

Multi-joint inflammation noted in RA patients increases the risk of fractures, thereby limiting the quality of life of affected subjects. Though several conventional synthetic and biologic DMARDs are available to alleviate joint inflammation and destruction, their joint protective effects are very minimal. Moreover, such treatments are associated with serious adverse events and the risk of infections since they suppress the immune system.

A recent systematic review and pooled analysis of randomized or matched data have reported that denosumab treatment helps in improving the BMD and reducing the progression of joint destruction in RA patients when compared to bisphosphonates.

The study considered 1758 patients and the results of the pooled analysis demonstrated that the denosumab treatment contributed to a significant increase in the bone mineral density of the lumbar spine, total hip and femoral neck as opposed to controls.

In addition, the treatment resulted in a substantial reduction in modified total Sharp score and modified Sharp erosion score. Subgroup analysis indicated the superiority of denosumab over bisphosphonates for improving bone mineral density and the reduction of joint destruction.

Denosumab is a fully-humanized monoclonal antibody, which acts specifically by binding to human receptor activator of nuclear factor kappa B ligand (RANKL). RANKL contributes to bone resorption and bone loss through decreased survival and activity of osteoclasts.

Denosumab is recognized as a safe and effective antiresorptive agent for the treatment of postmenopausal osteoporosis and metastatic cancers. Previous studies have shown that denosumab treatment assists in significant suppression of osteoporosis, increasing bone mineral density and preventing joint destruction.

Though initial studies could not prove any benefit by denosumab, later the focus was shifted to the management of osteoporosis. The present study is the first of the systematic review and pooled analysis evaluating the efficacy of denosumab in patients with RA. However, the present findings need confirmation in large randomized clinical trials.

References: Hu Q, Zhong X, Tian H and Liao P (2022) The Efficacy of Denosumab in Patients With Rheumatoid Arthritis: A Systematic Review and Pooled Analysis of Randomized or Matched Data. Front. Immunol. 12:799575.