Monitoring total-body inflammation and damage in joints and entheses: the first follow-up study of whole-body magnetic resonance imaging in rheumatoid arthritis

<p><b>Objective</b>: To investigate changes in whole-body magnetic resonance imaging (WBMRI) inflammatory and structural lesions in most joints and entheses in patients with rheumatoid arthritis (RA) treated with adalimumab.</p> <p><b>Methods</b>: WBMRI was obtained at weeks 0, 6, 16, and 52 in a 52 week follow-up study of 37 RA patients starting treatment with adalimumab. Readability and reliability of WBMRI were investigated for 76 peripheral joints, 23 discovertebral units, the sacroiliac joints, and 33 entheses. Changes in WBMRI joint and entheses counts were investigated.</p> <p><b>Results</b>: The readability of peripheral and axial joints was 82–100%, being less for elbows and small joints of the feet. For entheses, 72–100% were readable, except for entheses at the anterior chest wall, elbow, knee, and plantar fascia. The intrareader agreement was high for bone marrow oedema (BMO), bone erosion (80–100%), and enthesitis (77–100%), and slightly lower for synovitis and soft tissue inflammation (50–100%). All synovitis, BMO, and soft tissue inflammation counts decreased numerically during treatment. The 26-joint synovitis WBMRI count decreased significantly during the first 16 weeks for patients with a good European League Against Rheumatism (EULAR) response (from median 6 to 4, p < 0.05), but not for patients with a moderate or no EULAR response. There were no overall changes in structural lesions.</p> <p><b>Conclusions</b>: WBMRI allows simultaneous monitoring of most axial and peripheral joints and entheses in RA patients and can visualize a decrease in inflammatory counts during treatment. This first WBMRI follow-up study of patients with RA encourages further investigation of the usefulness of WBMRI in RA.</p

Predictive value of a multi-biomarker disease activity score for clinical remission and radiographic progression in patients with early rheumatoid arthritis: a post-hoc study of the OPERA trial

<p><b>Objectives</b>: Measurement of serum biomarkers at disease onset may improve prediction of disease course in patients with early rheumatoid arthritis (RA). We evaluated the multi-biomarker disease activity (MBDA) score and early changes in MBDA score for prediction of 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) remission and radiographic progression in the double-blinded OPERA trial.</p> <p><b>Method</b>: Treatment-naïve RA patients (N = 180) with moderate or high DAS28 were randomized to methotrexate (MTX) + adalimumab (n = 89) or MTX + placebo (n = 91) in combination with glucocorticoid injection into swollen joints. X-rays of hands and feet were evaluated at months 0 and 12 (n = 164) by the total Sharp van der Heijde score (TSS). The smallest detectable change (1.8 TSS units) defined radiographic progression (∆TSS ≥ 2). Clinical remission (DAS28-CRP < 2.6) was assessed at baseline and 6 months. MBDA score was determined at 0 and 3 months and tested in a multivariable logistic regression model for predicting DAS28 remission at 6 months and radiographic progression at 1 year.</p> <p><b>Results</b>: Baseline MBDA score was independently associated with radiographic progression at 1 year [odds ratio (OR) = 1.03/unit, 95% confidence interval (CI) = 1.01–1.06], and changes in MBDA score from baseline to 3 months with clinical remission at 6 months [OR = 0.98/unit, 95% CI 0.96–1.00). In anti-cyclic citrullinated peptide antibody (anti-CCP)-positive patients, 35 of 89 with high MBDA score (> 44) showed radiographic progression (PPV = 39%), compared with 0 of 15 patients (NPV = 100%) with low/moderate MBDA score (≤ 44) (p = 0.003).</p> <p><b>Conclusion</b>: Early changes in MBDA score were associated with clinical remission based on DAS28-CRP at 6 months. In anti-CCP-positive patients, a non-high baseline MBDA score (≤ 44) had a clinical value by predicting very low risk of radiographic progression at 12 months.</p

Effect of a treat-to-target strategy based on methotrexate and intra-articular betamethasone with or without additional cyclosporin on MRI-assessed synovitis, osteitis, tenosynovitis, bone erosion, and joint space narrowing in early rheumatoid arthritis: results from a 2-year randomized double-blind placebo-controlled trial (CIMESTRA)

<p><b>Objectives</b>: To investigate whether a treat-to-target strategy based on methotrexate (MTX) and intra-articular (IA) betamethasone suppresses magnetic resonance imaging (MRI)-determined measures of disease activity and reduces joint destruction in early rheumatoid arthritis (eRA) patients, and to investigate whether concomitant cyclosporin A (CyA) provides an additional effect.</p> <p><b>Method</b>: In the 2-year randomized, double-blind, treat-to-target trial CIMESTRA, 160 patients with eRA (< 6 months) were randomized to MTX, intra-articular betamethasone and CyA, or placebo CyA. A total of 129 patients participated in the MRI substudy, and had contrast-enhanced MR images of the non-dominant hand at months 0, 6, 12, and 24. MR images were evaluated for osteitis, synovitis, tenosynovitis, bone erosion, and joint space narrowing (JSN), using validated scoring methods.</p> <p><b>Results</b>: Significant reductions were seen at 6 months in all inflammatory parameters [synovitis, mean change –1.6 (p < 0.001, Wilcoxon), tenosynovitis, –3.5 (p < 0.001), and osteitis, –1.3 (p < 0.05)] and at 12/24 months in synovitis and tenosynovitis [–1.6/–2.2 and –3.6/–3.8, respectively; all p < 0.001]. MRI signs of inflammation were not fully eliminated, and increases in erosion and JSN scores were observed at 6 months [0.4 (p < 0.01)/0.1 (p < 0.05)], 12 months [0.8 (p < 0.001)/0.3 (p < 0.01)], and 24 months [1.0 (p < 0.001)/0.4 (p < 0.001)]. Clinical measures decreased significantly (p < 0.001) at all time points. There were no consistent statistically significant differences between treatment groups.</p> <p><b>Conclusions</b>: In this eRA treat-to-target trial, MTX and intra-articular glucocorticoids markedly reduced, but did not eliminate, MRI osteitis, synovitis, and tenosynovitis. Accordingly, minimal but statistically significant increases in bone erosion and JSN were observed. No additional effect of CyA was demonstrated.</p