Cost-effectiveness of etanercept treatment in early active rheumatoid arthritis followed by dose adjustment.

Objectives: To explore the cost-effectiveness of early biologic treatment, followed by dose-reduction in the case of remission, of active rheumatoid arthritis (RA), compared with standard treatment with methotrexate (MTX) in Sweden.Methods: Effectiveness (function, disease activity, erosions) in early RA for both alternatives was taken from a clinical trial comparing etanercept (ETA) combined with MTX to MTX alone. Patients discontinuing treatment can switch to another or their first biologic treatment. For patients in remission (Disease Activity Score [DAS28] < 2.6), ETA is reduced to half the dose. Return to full dose occurs when DAS28 reaches ≥ 3.2 again. Costs and utilities by level of functional capacity from an observational study are used. The model is analyzed as a micro-simulation and results are presented from the societal perspective for Sweden, for 10 years; costs (€2008) and effects are discounted at 3 percent. Sensitivity analysis was performed for the perspective, the time horizon, switching, and dose-reduction.Results: The main analysis conservatively assumes 50 percent switching at discontinuation. The cost per quality-adjusted life-year (QALY) gained with early ETA/MTX treatment is €13,500 (societal perspective, incremental cost of €15,500 and incremental QALYs of 1.15). With 75 percent switching, the cost per QALY gained was €10,400. Over 20 years, the cost per QALY gained was €8,200. Results were further sensitive to the time patients remained on half dose and the perspective.Conclusions and Policy Implications: This study combines clinical trial and clinical practice data to explore cost-effective treatment scenarios in early RA, including the use of biologics. Our results indicate that a situation where a considerable proportion of patients achieve remission, dose-adjustments will increase the cost-effectiveness of treatment

Calprotectin in rheumatic diseases

none7Calprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-α inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker.noneOmetto, Francesca; Friso, Lara; Astorri, Davide; Botsios, Costantino; Raffeiner, Bernd; Punzi, Leonardo; Doria, AndreaOmetto, Francesca; Friso, Lara; Astorri, Davide; Botsios, Costantino; Raffeiner, Bernd; Punzi, Leonardo; Doria, Andre

Pixel-based approach to assess contrast-enhanced ultrasound kinetics parameters for differential diagnosis of rheumatoid arthritis

Inflammatory rheumatic diseases are the leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high comorbidity, and increased mortality. The standard for diagnosing and differentiating arthritis is based on clinical examination, laboratory exams, and imaging findings, such as synovitis, bone edema, or joint erosions. Contrast-enhanced ultrasound (CEUS) examination of the small joints is emerging as a sensitive tool for assessing vascularization and disease activity. Quantitative assessment is mostly performed at the region of interest level, where the mean intensity curve is fitted with an exponential function. We showed that using a more physiologically motivated perfusion curve, and by estimating the kinetic parameters separately pixel by pixel, the quantitative information gathered is able to more effectively characterize the different perfusion patterns. In particular, we demonstrated that a random forest classifier based on pixelwise quantification of the kinetic contrast agent perfusion features can discriminate rheumatoid arthritis from different arthritis forms (psoriatic arthritis, spondyloarthritis, and arthritis in connective tissue disease) with an average accuracy of 97%. On the contrary, clinical evaluation (DAS28), semiquantitative CEUS assessment, serological markers, or region-based parameters do not allow such a high diagnostic accuracy

Grade and location of power Doppler are predictive of damage progression in rheumatoid arthritis patients in clinical remission by anti-tumour necrosis factor \u3b1

Objectives.: To investigate power Doppler (PD) signal, grade and location and their association with radiographic progression in RA patients in remission. Methods: . A prospective observational study was conducted in 125 consecutive RA patients in stable 28-joint DAS (DAS28) remission (\u2a7e6 months) achieved on anti-TNF-\u3b1. At baseline, patients in stable remission underwent radiographic and US examination of the wrists and MCP, PIP and MTP joints. Semi-quantitative PD scoring (0-3) was recorded. We scored PD according to two locations: capsular or within synovial tissue without bone contact (location 1) and with bone contact or penetrating bone cortex (location 2). Radiographic progression was evaluated at the 1 year follow-up and defined as a change in van der Heijde-modified total Sharp score >0. Risk ratios (RRs) of radiographic progression according to presence, grade and location of PD were calculated. Results: . Four patients were excluded because of missing data. At baseline, 59/121 (48.7%) patients had a PD signal in one or more joints. PD location 2 was found in 74.6% patients (44/59). At the 1 year follow-up, 17/121 patients experienced radiographic progression: all had PD signal in one or more joints at baseline (RR 2.47, P < 0.0001). Radiographic progression was associated with the following baseline US features: PD grade 2 (RR 4.58, P < 0.01), PD grade 3 (RR 3.49, P < 0.05), total PD score \u2a7e2 (sum of all PD scores) (RR 3.19, P < 0.0001) and PD location 2 (RR 3.49, P < 0.0001). Conclusion: . Higher PD grades and PD in contact with/or penetrating bone are associated with radiographic progression in patients in DAS28 remission

MR and CEUS monitoring of patients with severe rheumatoid arthritis treated with biological agents: a preliminary study

PURPOSE: This study was done to propose a study protocol for patients with rheumatoid arthritis (RA) treated with biological agents, by evaluating the contribution of contrast-enhanced magnetic resonance (CE-MR) imaging, a software programme that calculates the volume of synovitis on CE-MR images, and contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Sixteen patients with RA receiving treatment with biologics were analysed. The patients underwent clinical examination, CE-MR imaging and CEUS on the same day. Images were postprocessed with the software and evaluated independently by three physicians in terms of RAMRIS (Rheumatoid Arthritis Magnetic Resonance Imaging Score), SAMIS (Simplified Rheumatoid Arthritis Magnetic Resonance Imaging Score) and CEUS grade. The techniques were correlated statistically. RESULTS: The RAMRIS and SAMIS scores were found to correlate statistically. CE-MR imaging correlated with the clinical data (p < 0.05), whereas CEUS did not. The data provided by the software did not correlate statistically with the other techniques. The most painful joint was consistently found to be the joint with most synovitis. CONCLUSIONS: CE-MR imaging may be used prior to treatment and for long-term follow-up. CEUS might be useful in the short-term follow-up, as it seems to provide an indication of the presence or absence of disease, though not of its severity. The software is a very useful tool that can supplement, but not replace, the other techniques

Predictors, Features and Effects of First Biologic Switch in Rheumatoid Arthritis within GISEA register: Italian 10-Year Experience

The study investigated the predictors and the effects of treatment with a second biologic agent in rheumatoid arthritis patients. Data were collected in the GISEA register, an Italian registry that covered 10 years

Longterm retention of tumor necrosis factor-α inhibitor therapy in a large italian cohort of patients with rheumatoid arthritis from the GISEA registry: an appraisal of predictors

OBJECTIVE: To evaluate 4-year retention rates of tumor necrosis factor-α (TNF-α) inhibitors adalimumab, etanercept, and infliximab among patients with longstanding rheumatoid arthritis (RA), as derived from an Italian national registry.METHODS: The clinical records of 853 adult patients with RA in the GISEA (Gruppo Italiano Studio Early Arthritis) registry were prospectively analyzed to compare drug survival rates and the baseline factors that may predict adherence to therapy.RESULTS: In 2003 and 2004, 324 patients started treatment with adalimumab, 311 with etanercept, and 218 with infliximab. After 4 years, the global retention rate of anti-TNF-α therapy was 42%. Etanercept survival (51.4%) was significantly better than that of infliximab (37.6%) or adalimumab (36.4%; p < 0.0001). Accordingly, the mean duration of therapy was significantly longer for etanercept (3.1 ± 2 yrs) than for adalimumab (2.6 ± 2 yrs) or infliximab (2.7 ± 2 yrs; p < 0.05). The use of concomitant disease-modifying antirheumatic drugs, mainly methotrexate, and the presence of comorbidities significantly predicted drug continuation (p < 0.01), whereas a high Disease Activity Score did not.CONCLUSION: The 4-year global drug survival of adalimumab, etanercept, and infliximab was lower than 50%, with etanercept having the best retention rate. The main positive predictor of adherence to anti-TNF-α therapy was the concomitant use of methotrexate. Our study provides further evidence that the real-life treatment of patients with RA may be different from that of randomized clinical trials

Long-term anti-TNF therapy and the risk of serious infections in a cohort of patients with rheumatoid arthritis: Comparison of adalimumab, etanercept and infliximab in the GISEA registry

Objective: To evaluate the risk of serious infections (SIs) in RA patients receiving anti-TNF therapy on the basis of the data included in the GISEA register. Methods: The study involved 2769 adult patients with long-standing RA (mean age 53.2 ± 13.4 years; mean disease duration 9.0 ± 8.3 years) enrolled in the GISEA register, who had been treated for at least 6 months with TNF inhibitors or had discontinued therapy due to SI: 837 (30%) treated with infliximab (IFN), 802 (29%) with adalimumab (ADA), and 1130 (41%) with etanercept (ETN). Results: 176 patients had experienced at least one of the 226 Sis during the 9 years of treatment with an anti-TNF agent, an overall incidence of 31.8/1000 patient-years (95% CI 25.2-38.3): 23.7/1000 patient-years (95% CI 13.1-34.2) on ADA; 12.8/1000 patient-years (95% CI 6.3-19.4) on ETN and 65.1/1000 patient-years (95% CI 48.4-81.8) on IFN. The risk was higher in the first than in the second year of treatment, but this difference was not statistically significant (p = 0.08) (38.9% of the SIs were recorded in the first 12 months of treatment). The risk of SI was significantly different among the three treatment groups (p b 0.0001). Multivariate models confirmed that the use of steroids (p b 0.046), concomitant DMARD treatment during anti-TNF therapy (p = 0.004), advanced age at the start of anti-TNF treatment (p b 0.0001), and the use of IFN or ADA rather than ETN (respectively p b 0.0001 and p = 0.023) were strong and statistically significant predictors of infection. Conclusions: Anti-TNF therapy is associated with a small but significant risk of SI that is associated with the concomitant use of steroids, advanced age at the start of anti-TNF treatment, and the type of anti-TNF agent