Abstract 698: Denosumab Inhibits RANKL, Reducing Progression of the Total Sharp Score and Bone Erosions in Patients With Rheumatoid Arthritis: 12-month X-Ray Results
Authors
van der Heijde D, Cohen S, Sharp JT, Ory P, Zhou L, Tsuji W, Newmark R
Background:
Denosumab (previously AMG 162) is a fully human IgG2 monoclonal antibody that binds RANKL thus inhibiting osteoclast formation, function, and survival. RANKL-driven osteoclast activity is important in bone erosions of rheumatoid arthritis (RA), bone resorption in osteoporosis, and metastatic bone disease. At EULAR 2007 data from this study was also presented from this ongoing study including 12 month plain radiographic results. We have reported on the results from this study at ACR 2006 showing a significant reduction in bone erosions by MRI at 6 months with a single dose of denosumab 180 mg.
Methods:
227 patients were randomized to injections of denosumab 60 mg or 180- mg or placebo every 6 months. Changes from baseline to 6 and 12months in radiographic assessments using van der Heijde-modified total Sharp score (TSS) of hand and feet X-rays and its components (erosion and joint space narrowing) were evaluated.
Results:
202 patients (89%) completed 12 months of study. The results of observed radiographic changes are in the table below. These radiographic erosion scores were consistent with previously reported MRI erosion scores. There was no significant effect on signs and symptoms. Adverse events were similar across the 3 treatment groups.
| Change in Radiographic Score at 12 Months |
|||
Measurement (Mean (SD)) |
Placebo |
Denosumab 60 mg |
Denosumab 180 mg |
|
n = 71 |
n = 69 |
n = 69 |
Total Sharp Score |
1.87 (5.06) |
0.85 (2.52)* |
0.97 (2.70)† |
Erosion Score |
1.34 (4.40) |
0.33 (1.22)# |
0.19 (1.61)# |
Joint Space Narrowing |
0.53 (1.49) |
0.51 (1.63) |
0.78 (1.72) |
*P = 0.03 vs. placebo, †P = 0.18 vs. placebo #P < 0.05 vs. placebo.
Conclusion:
Denosumab treatment (60 mg and 180 mg) every 6 months reduced progression of radiographic TSS and bone erosions compared with placebo, with no effect on cartilage, and with an adverse event profile similar to placebo.
Editorial Comment:
The studies of denosumab in RA demonstrate the potential for a selective osteoclast inhibitor as part of the treatment regimen. These 6 and 12 month plain radiographic results support earlier MRI studies. Where this compound will fit into the RA treatment armamentarium is unclear. The compound has no effect on signs and symptoms or salutary effects on cartilage. However, its ability to slow erosions without the concomitant infectious side effects of other immunosuppressive agents may give it a position in halting erosions at early stages of the disease while other DMARDS are introduced. There may be an additional role in helping to prevent steroid-induced osteoporosis.
