by Dr. C.H. Weaver M.D. 5/2019
Recent research suggests that combining Prolia (denosumab) with a conventional disease-modifying antirheumatic drug (DMARD) such as methotrexate shows promise for slowing radiographic damage in rheumatoid arthritis (RA) according to the recently published phase III clinical trial called DESIRABLE.
Prolia is a monoclonal antibody that inhibits the receptor activator of nuclear factor ΚB ligand (RANKL) that is used for the treatment of osteoporosis. Binding of RANKL suppresses bone resorption and may help slow the progression of bone erosions. Earlier clinical trials have demonstrated significant inhibition of bone erosions in patients with RA who were also given methotrexate.
Dr. Takeuchi and colleagues in Japan designed a clinical trial to test Prolia. In the clinical trial they enrolled 654 patients between 2013 to 2015 who were taking methotrexate or other conventional DMARDs but had not received previous treatment with biologics. Individuals were treated with different doses of Prolia or placebo and directly compared using radiographs of the hands and feet at the “Sharp” score obtained at baseline, 6 months, and 1 year.
At the one year evaluation patients who were treated with Prolia had an improvement from baseline in their total Sharp score, were less likely to exhibit radiographic changes consistent with joint erosion, and experienced improved bone mineral density at the lumbar spine.
The study results suggest that RANKL inhibition with Prolia can be adjunctive therapy to protect bone, but would not be a replacement for existing anti-inflammatory, disease-modifying, or biologic therapy. Additional research is ongoing to identify which patients are most appropriate for Prolia treatment and to determine the optimal duration of therapy.
Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial