Treatment with Denosumab 60 mg and 180 mg, ( associated with Methotrexate ) reduces the progression of bone erosion.

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 associated bone erosions.

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 rheumatoid arthritis associated bone erosion.

Researchers gathered data on erosion score, joint space narrowing and derived the van der Heijde modified Total Sharp Score ( TSS ).
The van der Heijde modified Total Sharp Score is a method by which to evaluate joint destruction of rheumatoid arthritis patients, which is calculated based on erosion score and joint space narrowing from bone x-rays. An increase in TSS denotes an increase in damage to the joints being assessed which is associated with a worsening of symptoms. An increase in erosion score denotes a worsening in disease progression.

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 rheumatoid arthritis on background Methotrexate.

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.

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.

Source: European League Against Rheumatism ( EULAR ), 2007

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