Power Doppler ultrasonography is useful for assessing disease activity and predicting joint destruction in rheumatoid arthritis patients receiving tocilizumab—preliminary data

To evaluate the responsiveness of power Doppler ultrasonography (PDUS) in comparison with conventional measures of disease activity and structural damage in rheumatoid arthritis (RA) patients receiving tocilizumab (TCZ). Seven RA patients with active arthritis were enrolled in the study and prospectively monitored for 12 months. They were treated with TCZ (8 mg/kg) every 4 weeks as monotherapy or in combination with disease-modifying antirheumatic drugs (DMARDs). Clinical, laboratory, and ultrasound examinations were conducted at baseline, 1, 3, 6, 9, and 12 months. Power Doppler (PD) signals were graded from 0 to 3 in 24 joints, and total PD score was calculated as the sum of scores of individual joints. One-year radiographic progression of the hands was estimated by using Genant-modified Sharp scoring. The averages of the clinical parameters rapidly improved, and all patients achieved good response within 6 months based on standard 28-joint Disease Activity Score (DAS28). Although the average total PD score declined in parallel with clinical improvement, radiography of the hands showed progression of destruction in the joints where PD signals remained, even among clinical responders. ΔSharp score correlated with the time-integrated value (TIV) of total PD scores (Δtotal Sharp score: r = 0.77, P = 0.04; Δerosion: r = 0.78, P = 0.04; Δjoint-space narrowing (JSN): r = 0.75, P = 0.05), but not with TIVs of clinical parameters including DAS28. PDUS can independently evaluate disease activity in RA patients receiving TCZ and is superior to DAS28, especially in predicting joint destruction

Deep-inspiration breath-hold ¹⁸F-FDG-PET/CT is useful for assessment of connective tissue disease associated interstitial pneumonia

<div><p></p><p><i>Objective</i>: To examine clinical utility of ¹⁸F-flurodeoxyglucose (FDG)-positron emission tomography (PET)/CT for assessment of interstitial lung disease (ILD) in patients with connective tissue diseases (CTDs).</p><p><i>Methods</i>: A total of 69 ¹⁸F-FDG PET/CT scans were conducted under deep inspiratory breath hold (DIBH) conditions in 45 CTD patients with ILD, including 16 dermatomyositis/polymyositis, nine systemic scleroderma and seven rheumatoid arthritis. Intensity and distribution of ¹⁸F-FDG signals in PET/CT were determined by standardized uptake value (SUVmax) and visual score in 18 regions, respectively. ILD was defined as active when immunosuppressive therapy was initiated or intensified.</p><p><i>Results</i>: Both SUVmax and visual score were higher in active phase (<i>n = </i>32) than inactive phase (<i>n = </i>37) (both <i>p</i> < 0.05), regardless of the underlying CTD and plain CT findings. The both parameters reduced after initiating or intensifying treatment in the follow-up study of 17 active patients except two died patients who showed increased visual score. Another two died patients showed high visual score (15 and 6/18, respectively). Changing ratio of visual score, but not SUVmax was correlated with KL-6 (<i>r</i>² = 0.38, <i>p</i> < 0.05) and CRP (<i>r</i>² = 0.52, <i>p</i> < 0.05).</p><p><i>Conclusion</i>: The DIBH ¹⁸F-FDG PET/CT procedure sensitively illustrates active ILD lesions in CTD and the extended signal distribution is associated with unfavorable clinical outcome.</p></div

Effects of HSP60 and LPS on HO-1 protein expression in PBMCs from patients with BD

Effect of lipopolysaccharide (LPS) stimulation on heme oxygenase (HO)-1 and actin protein expression in peripheral blood mononuclear cells (PBMCs) from patients with Behçet's disease (BD). PBMCs from a BD patient were stimulated with LPS in the presence or absence of 10 ng/ml interleukin (IL)-10 and 100 μg/ml polymyxin B (PMB). Representative immunoblotting data for HO-1 protein in the cells are shown. The arrowhead indicates 32 kDa molecular weight HO-1 specific band. Effect of heat shock protein (HSP)60 (3 μg/ml) stimulation on endogenous HO-1 protein expression in PBMCs from patients with BD. The arrowhead indicates 32 kDa HO-1 specific band. A representative of three independent experiments is shown. Mean and standard error of the mean (SEM) values of HO-1 and actin protein expression in PBMCs stimulated by LPS (1 ng/ml) for 24 hours in patients with BD (= 14). < 0.001, as determined using paired -test. Effect of infliximab (10 μg/ml) or IgGκ (10 μg/ml) on HO-1 expression in LPS (10 ng/ml) or tumor necrosis factor (TNF; 1 ng/ml) treated PBMCs.<p><b>Copyright information:</b></p><p>Taken from "Association of reduced heme oxygenase-1 with excessive Toll-like receptor 4 expression in peripheral blood mononuclear cells in Behçet's disease"</p><p>http://arthritis-research.com/content/10/1/R16</p><p>Arthritis Research & Therapy 2008;10(1):R16-R16.</p><p>Published online 31 Jan 2008</p><p>PMCID:PMC2374472.</p><p></p

Head-to-head comparison of the safety of tocilizumab and tumor necrosis factor inhibitors in rheumatoid arthritis patients (RA) in clinical practice: Results from the registry of Japanese RA patients on biologics for long-term safety (REAL) registry

Introduction: The objective of this study was to directly compare the safety of tocilizumab (TCZ) and TNF inhibitors (TNFIs) in rheumatoid arthritis (RA) patients in clinical practice. Methods: This prospective cohort study included RA patients starting TCZ [TCZ group, n = 302, 224.68 patient-years (PY)] or TNFIs [TNFI group, n = 304, 231.01 PY] from 2008 to 2011 in the registry of Japanese RA patients on biologics for long-term safety registry. We assessed types and incidence rates (IRs) of serious adverse events (SAEs) and serious infections (SIs) during the first year of treatment. Risks of the biologics for SAEs or SIs were calculated using the Cox regression hazard analysis. Results: Patients in the TCZ group had longer disease duration (P <0.001), higher disease activity (P = 0.019) and more frequently used concomitant corticosteroids (P <0.001) than those in the TNFI group. The crude IR (/100 PY) of SIs [TCZ 10.68 vs. TNFI 3.03; IR ratio (95% confidence interval [CI]), 3.53 (1.52 to 8.18)], but not SAEs [21.36 vs. 14.72; 1.45 (0.94 to 2.25)], was significantly higher in the TCZ group compared with the TNFI group. However, after adjusting for covariates using the Cox regression hazard analysis, treatment with TCZ was not associated with higher risk for SAEs [hazard ratio (HR) 1.28, 95% CI 0.75 to 2.19] or SIs (HR 2.23, 95% CI 0.93 to 5.37). Conclusions: The adjusted risks for SAEs and SIs were not significantly different between TCZ and TNFIs, indicating an influence of clinical characteristics of the patients on the safety profile of the biologics in clinical practice

Effect of forced HO-1 expression on Toll-like receptor (TLR)2 and TLR4 mRNA expression in peripheral monocytes

Immunoblotting analysis of heme oxygenase (HO)-1 and actin in pHO-1 (human HO-1 expression vector) or pCont (control vector) transfected monocytes. The arrow represents HO-1 protein. Real-time PCR analysis of TLR2 and TLR4 mRNA expression in pHO-1 transfected peripheral blood mononuclear cells (PBMCs). NS, not significant.<p><b>Copyright information:</b></p><p>Taken from "Association of reduced heme oxygenase-1 with excessive Toll-like receptor 4 expression in peripheral blood mononuclear cells in Behçet's disease"</p><p>http://arthritis-research.com/content/10/1/R16</p><p>Arthritis Research & Therapy 2008;10(1):R16-R16.</p><p>Published online 31 Jan 2008</p><p>PMCID:PMC2374472.</p><p></p