Abstract 268: Anti-TNF Treatment with Adalimumab Reduces Hand Bone Loss in Early Rheumatoid Arthritis (RA): Explorative Analyses from the Premier Study
Authors
M Hoff, TK Kvien, J Kälvesten, J Algulin, A Elden, G Haugeberg
Background:
Periarticular osteoporosis and erosions are features of bone damage in RA. There is limited information however concerning the effects of TNF antagonists on osteoporosis and bone loss. The aim of this study was to compare hand bone loss across the three treatment arms of the PREMIER study (Breedveld et al A&R 2006;54: 26-37).
Methods:
The PREMIER study compared adalimumab + methotrexate (MTX) versus MTX alone and adalimumab alone in early active, MTX-naive RA patients. Digital x-ray radiogrammetry (DXR, SECTRA) was used to measure metacarpal cortical index (MCI) from digitized hand X-rays. MCI, defined as the combined metacarpal cortical thickness divided by the outer bony diameter, has been shown to be highly correlated with bone mass. MCI percentage change from baseline to 26, 52 and 104 weeks were calculated. Non-parametric group comparisons and correlation analyses between MCI change at 104 weeks and demographic and clinical variables were performed. Variables with p-value <0.10 were tested in a linear regression model.
Results:
Baseline characteristics in the 769 patients were similar across treatment groups. Median hand bone loss was greater in the MTX vs. the MTX + adalimumab group at 26 weeks (1.4 vs. 1.1%, p=0.19), at 52 weeks (2.9 vs. 2.2%, p<0.001) and at 104 weeks (4.6 vs. 3.0%,p<0.001). The magnitude of hand bone loss in the adalimumab alone group was between the two other groups (1.3%, 2.5% and 4.0%, respectively), with a trend towards a significant difference versus MTX (p= 0.09) and the combination group (p=0.07) at 104 weeks. Predictors of cortical hand bone loss at 104 weeks were older age, high CRP and use of MTX versus anti-TNF. Decrease in hand cortical bone loss and increasing in radiographic damage were moderately correlated, r=0.12, 0.23 and 0.32 at 26, 52 and 104 weeks respectively (p<0.001 for all).
Conclusion:
The effects of adalimumab on cortical bone loss at the hand measured from Digital XRay radiogrammetry were similar to the effects on radiographic damage reported in the clinical trial, with more bone loss in methotrexate alone, and the least loss in the group treated with MTX + adalimumab.
Editorial comment:
This is an interesting study done post hoc from images obtained in a large clinical trial showing an apparent partial protection from cortical bone loss with adalimumab in combination with MTX. These results are not surprising given that TNF acts to induce RANKL, and inhibition of RANKL has been associated with increased cortical bone density. However the results reported here with adalimumab contrast with results reported last year with infliximab in which BMD at multiple sites, and evaluation of cortical bone at the wrist using Digital radiogrammetry as in this study were analyzed (Vis M, Havaardsholm EA, Haugeberg G, Uhlig T, Voskuyl AE, van de Stadt RJ, Dijkmans BA, Woolf AD, Kvien TK, Lems WF. Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NFkappaB ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2006 Nov;65(11):1495-9. Epub 2006 Apr 10.) In that study, while infliximab favorably affected BMD at the hip and spine, there was no effect on cortical bone at the wrist. These contrasting results on cortical bone density from two different TNF antagonists should be further explored. Nonetheless it remains encouraging that TNF antagonism may have beneficial effects on bone density in general.
