Treatment with denosumab 60 mg and 180 mg, with background methotrexate, reduces the progression of bone erosion according to results of a 227 patient-Phase II trial presented today at EULAR 2007, the Annual European Congress of Rheumatology in Barcelona, Spain.
Denosumab is a fully human monoclonal antibody which binds to and inhibits the RANK Ligand. The RANK Ligand is the essential mediator of osteoclast formation, function, and survival and thereby plays a key role in rheumatoid arthritis (RA) associated bone erosions (osteoclasts are the cells responsible for the break down of bone material).
Bone status in patients? hands and feet was assessed by radiographs at initiation of trial, six and 12 months to assess the capacity of denosumab to reduce progression of RA associated bone erosion. Researchers gathered data on erosion score (a measure of damage to joints), joint space narrowing (a measure of reduced space between bones in each joint) and derived the van der Heijde modified Total Sharp Score (TSS) (see Editors note).
Professor D?sir?e van der Heijde of Leiden University Medical Center and lead author of the study commented, ?These data show the significant potential of denosumab, revealing that patients receiving denosumab experienced a reduced progression of erosions compared to control. Most significant was the difference observed between the control group and the group receiving denosumab 180mg. The reduction in progression of erosions was already present in this group as early as 6 months.?
In the double-blind, placebo-controlled, phase II study, 227 patients were randomly assigned to receive subcutaneous denosumab injections or placebo at initiation of trial, and after six months, to determine if denosumab could reduce the progression of bone erosions in patients with RA on background methotrexate (MTX ? standard RA treatment).
Mean erosion scores were significantly reduced for the groups treated with denosumab compared to the control group. Change in mean erosion score at 12 months was reported as 0.33 and 0.19 for treatment with denosumab 60 mg and 180 mg respectively, compared with the change in score for the control group of 1.34 (respective p= 0.01 and p= 0.007). For the 180mg group the reduction in progression in erosions was already significantly less as compared to the control group after 6 months (0.05 vs. 0.59, p-value = 0.02) and a trend was seen in the 60 mg group (0.25).
An increase in TSS was observed in the control group of patients at 12 months, significantly higher than that observed in patients in the treatment groups. For patients receiving denosumab, the progression in TSS at 12 months was 0.85 and 0.97 for denosumab 60mg and 180mg respectively as compared to 1.87 for the control group (respectively, p=0.03 and p=0.18). No specific differences in the in Joint Space Narrowing (JSN) were detected between the denosumab and the control groups.
In this study, safety was continually monitored and an adverse event profile similar to that of patients receiving placebo was observed in patients receiving treatment with denosumab.