ADALIMUMAB REDUCES HAND BONE LOSS IN RHEUMATOID ARTHRITIS (RA) INDEPENDENT OF CLINICAL RESPONSE: SUBANALYSIS OF THE PREMIER STUDY

Background: Adalimumab reduces the rates of both radiographic joint damage and hand bone loss in patients with early RA.1,2 The rate of radiographic joint progression has even been shown to be reduced independent of patient's clinical response to adalimumab. This has previously not been examined for hand bone loss, the second feature of bone involvement in inflammatory RA. Objectives: To examine relationship between hand bone loss and clinical response for patients receiving methotrexate (MTX) monotherapy and for patients receiving adalimumab plus MTX in the PREMIER study. Methods: The PREMIER study compared the efficacy of adalimumab plus MTX vs. MTX alone and adalimumab alone in early (<3 yrs), active, MTX-naive RA patients. This subanalysis involved the MTX monotherapy and the combination therapy groups. Hand bone loss was assessed by digital X-ray radiogrammetry metacarpal cortical index (DXR-MCI), calculated from digitized radiographs (DXR, Sectra, Sweden). MCI, defined as the combined metacarpal cortical thickness divided by the outer bony diameter, has been shown to be well-correlated with bone mineral density. MCI percentage change from baseline to 52 weeks was evaluated for patients with different clinical response. Disease activity was assessed by DAS28 scores at 52 weeks for 4 subgroups: Remission = DAS28<2.60; Low disease activity = DAS28 2.61–3.20; Moderate disease activity = DAS28 3.21–5.10; and high disease activity = DAS28>5.10. Non-parametric group comparisons were performed. Results: For the combination group, there were no difference between bone loss in RA patients with remission, low, moderate, and high disease activity (p= 0.97). For the MTX group, there were numerical differences between the 4 clinical disease activity subgroups (p=0.10) (table). Because of a small numbers of patients in some of the 4 subgroups, we further divided patients into 2 other subgroups: remission and low disease activity vs. moderate and high disease activity. In the MTX group, patients with moderate and high DAS28 lost significantly more DXR-MCI than patients with low DAS 28 (median: –3.30 vs. –2.15, p=0.01), while no statistically significant difference was seen in the combination group (–1.86 vs. –2.37, p=0.99). Correlation between disease activity and hand bone loss (percentage DXR-MCI) was –0.14 (p=0.06) in the MTX group and –0.07 (p=0.33) for the combination group. Disease activityMTXMedian (mean)ADALIMUMABMedian (mean) N=185% DXR-MCI change+ MTX (N=208)% DXR-MCI change Remission DAS28 ≤ 2.6051-2.14 (-2.99)110-2.44 (-2.72) Low DAS28: 2.61-3.2031-2.20 (-2.98)38-1.94 (-2.62) Moderate DAS28: 3.21-5.1079-3.33(-4.65)51-2.01 (-3.17) High DAS28 > 5.1024-3.02(-4.64)9-1.63 (-2.72) Conclusion: These data suggest that adalimumab reduces hand bone loss independent of clinically assessed disease activity as previously shown for radiographic joint damage. This disconnection between inflammation and bone loss was not seen in MTX monotherapy treated patients. This results support the hypothesis that TNF influences bone loss not only by stimulating RANKL by inflammation, but also by activating the osteoclast directly. References: 1. Breedveld et al. The PREMIER study. A&R 2006; 54:26-37. 2. Hoff et al Adalimumab therapy reduces hand bone loss in early RA. ARD 2008 Sep 18.E-pub Disclosure of Interest: M. Hoff, TK Kvien and G. Haugeberg have received consulting fees as speakers from Abbott Lab. TK Kvien, A Kavanaugh and G. Haugeberg have received funding for independent research from Abbott Lab. Aake Elden is employed by Abbott Lab. Johan Kälvesten is employed by Sectra.Citation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 425Session: Rheumatoid arthritis Anti-TNF therapy (Poster Presentations )