Abstract
BackgroundAnti-TNF therapy has been shown to reduce radiographic joint damage in rheumatoid arthritis (RA) independent of clinical response. This has previously not been examined for periarticular bone loss, the other characteristic feature of bone involvement in RA.The objective of this study was to examine if treatment with the TNF-α inhibitor adalimumab also could reduce periarticular bone loss in RA patients independent of disease activity.MethodsRA patients were recruited from the PREMIER study and included 214 patients treated with methotrexate (MTX) plus adalimumab and 188 patients treated with MTX monotherapy. Periarticular bone loss was assessed by digital X-ray radiogrammetry metacarpal cortical index (DXR-MCI). Change in DXR-MCI was evaluated in patients with different levels of clinical response, as assessed by changes in DAS28 score at 52 weeks and in mean C-reactive protein (CRP) levels during follow-up.ResultsIn the MTX group, there was a greater median DXR-MCI loss among patients with moderate and high disease activity compared to those in remission or with low disease activity (-3.3% vs. -2.2%, p = 0.01). In contrast, periarticular bone loss was independent of disease activity (-1.9% vs. -2.4%, p = 0.99) in the combination group. In the MTX group patients with a mean CRP of ≥ 10 mg/l lost significantly more DXR-MCI than patients with low CRP (-3.1% vs. -1.9%, p <0.01) whereas in the combination group no significant differences between the two CRP groups was seen (-2.4% vs. -2.0%, p = 0.48).ConclusionAdalimumab in combination with MTX reduces periarticular bone loss independently of clinical response. These results support the hypothesis that TNF-α stimulates the osteoclast not only by the inflammatory pathway but do also have a direct effect on the osteoclast.Trial RegistrationClinicalTrials (NCT): NCT001195663
Highlights
Anti-TNF therapy has been shown to reduce radiographic joint damage in rheumatoid arthritis (RA) independent of clinical response
The PREMIER study cohort was used to examine the relationship between periarticular bone loss and clinical response in RA patients treated with MTX and anti TNF-therapy
The clinical, radiographic and bone density data from this 2-year, multi-centre, double-blind, randomised controlled study has previously been described in detail [6,9] In short, the efficacy and safety of adalimumab plus MTX was compared with adalimumab monotherapy and with MTX monotherapy in 799 adult patients with early (< 3 years, mean disease duration 9.1 month), aggressive RA (inclusion criteria: ≥8 swollen joint; erythrocyte sedimentation rate ≥28 or C-reactive protein (CRP) ≥1.5 mg/ dl; erosions or rheumatoid factor positive), who previously had not been treated with MTX [9]
Summary
Anti-TNF therapy has been shown to reduce radiographic joint damage in rheumatoid arthritis (RA) independent of clinical response This has previously not been examined for periarticular bone loss, the other characteristic feature of bone involvement in RA. Substantial data support that both erosions and osteoporosis in RA share a common cellular pathway which involves stimulation of the osteoclast This osteoclast activation depends on stimulation from receptor activator of nuclear factor- ligand (RANKL) which binds to the receptor activator of nuclear factor- (RANK) on the osteoclast. The rate of radiographic joint progression was reported to be reduced independent of a patient’s clinical response to anti-TNF therapy [7,8] This may suggest an additional positive effect of anti-TNF therapy on bone in RA independent of its anti-inflammatory effect.
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