Serum Calprotectin Discriminates Subclinical Disease Activity from Ultrasound-Defined Remission in Patients with Rheumatoid Arthritis in Clinical Remission.

OBJECTIVE: Clinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation. METHODS: Seventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0-1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves. RESULTS: The total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58-67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 µg/mL, p<0.005). Using ultrasound-defined remission criteria, calprotectin had an AUC of 0.692, p<0.05 using DAS28-ESR remission criteria and an AUC of 0.712, p<0.005 using DAS28-CRP remission criteria. Calprotectin correctly distinguished ultrasound remission from subclinical activity in 70% of patients. CRP (AUC DAS28-ESR = 0.494, p = NS; AUC DAS28-CRP = 0.498, p = NS) had lower and insignificant discriminatory capacity. CONCLUSION: The present study demonstrates the potential of calprotectin to distinguish RA patients in both clinical and ultrasound-defined remission from patients in clinical remission but with residual subclinical disease activity.

A tailored approach to reduce dose of anti-TNF drugs may be equally effective, but substantially less costly than standard dosing in patients with ankylosing spondylitis over 1 year: a propensity score-matched cohort study.

OBJECTIVE: To compare the effectiveness, safety and costs of standard versus individually tailored reduced doses of anti-tumour necrosis factor (TNF) drugs in patients with ankylosing spondylitis (AS) after achieving low-disease activity. METHODS: This was a single-centre prospective observational study performed within the ATTRA registry. The anti-TNF dose tapering strategy was chosen by treating physicians, without prespecified protocol. We used propensity score (PS) methodology to identify two cohorts of patients matched for relevant baseline characteristics who were treated with either reduced (n=53) or standard (n=83) doses of TNF inhibitors. One-year outcomes and costs of anti-TNF drugs were compared between both PS-matched cohorts. RESULTS: In the reduced dosing group, the median dose of TNF inhibitor corresponded to 0.67 and 0.5 of the standard dose initially and at 12 months respectively, and 21% of patients required return to standard dosing regimen. The mean change per year in Bath Ankylosing Spondylitis Activity Index, C-reactive protein , Health Assessment Questionnaire Disability Index and Bath AS functional index, as well as quality-adjusted life-year area under the curve were no different between both groups. The HR (95% CI) of reduced versus standard dosing group for relapse and any adverse event was 1.46 (0.66 to 3.19) and 0.56 (0.22 to 1.44), respectively. Mean difference (95% CI) in cost of anti-TNF drugs was €-4214 (-4707 to -3701) per year of treatment in favour of reduced dosing strategy. CONCLUSIONS: In patients with AS after reaching low-disease activity, a tailored approach to reduce doses of anti-TNF drugs produced similar clinical outcomes at 1 year, but was substantially less costly.

High levels of metastasis-inducing S100A4 protein and treatment outcome in early rheumatoid arthritis: data from the PERAC cohort.

Abstract The aim of this study was to evaluate the role of S100A4 as a biomarker in patients with early rheumatoid arthritis (RA). S100A4 levels were measured in 59 patients with early RA and in 41 healthy controls. The association between the S100A4 levels and the treatment outcome after 12 months was determined using multivariate regression analysis. Serum S100A4 levels were significantly higher in the patients with early RA than in the healthy subjects and significantly decreased after 3 months of treatment. Diseases activity at 12 months was significantly higher in female patients who had initially high levels of S100A4. Persistently high S100A4 levels predicted poor treatment outcome and S100A4 may thus represent promising biomarker for assessing treatment response in patients with RA.

Quantiferon TB Gold and tuberculin skin tests for the detection of latent tuberculosis infection in patients treated with tumour necrosis factor alpha blocking agents.

OBJECTIVES: The risk of activation of latent tuberculosis infection (LTBI) is increased in patients treated with anti-TNF-α drugs. Tuberculin skin test (TST) and Quantiferon-TB Gold test (QFT) are used to detect LTBI before and during anti-TNF-α treatment. We describe here a relation of these tests at various timepoints and also longitudinal QFT data. METHODS: Study group consisted of 305 patients with several rheumatic inflammatory diseases treated and/or scheduled for anti-TNF-α drugs. The QFT was performed in 303 patients during therapy and in 177 patients also during screening. The TST was used in 284 patients. Both tests simultaneously were utilised in 360 instances. RESULTS: Twenty-two patients were QFT positive; 3.9% before and 5.9% during anti-TNF-α treatment. Two patients who became QFT positive developed active tuberculosis. The TST was positive in 42% and 38% of patients before and during treatment, respectively. There was poor agreement between the two tests. Patients on glucocorticoids had a negative TST more frequently. The IFN-γ response to mycobacterial antigens significantly increased after application of tuberculin, but never reached the positive threshold. There was a significant increase in mitogen-induced IFN-γ production after initiation of anti-TNF-α therapy. CONCLUSIONS: Poor correlation between the QFT and TST renders the TST non-specific for LTBI. QFT is more specific to detect LTBI and conversion to a positive result may predict active TB. An increase in IFN-γ production in response to mycobacterial antigens is seen when the TST is performed before the QFT. Mitogen-induced IFN-γ production increases after initiation of anti-TNF-α therapy.

The level of serum visfatin (PBEF) is associated with total number of B cells in patients with rheumatoid arthritis and decreases following B cell depletion therapy.

OBJECTIVE: Visfatin, also known as pre-B cell colony-enhancing factor, was recently characterized as a potent pro-inflammatory mediator in rheumatoid arthritis (RA). The aim of this study was to determine the effect of B cell depletion with rituximab on serum visfatin levels in patients with active RA. METHODS: We evaluated 31 patients with RA starting rituximab therapy at baseline and after 16 and 24 weeks using disease activity score (DAS28). The control group consisted of 33 gender and age-matched healthy individuals. CD19(+) B cells were assessed by flow cytometry and serum levels of visfatin and B cell-activating factor of the TNF family (BAFF) were measured by ELISA at baseline and week 16. RESULTS: Total number of B cells correlated positively with serum visfatin levels (rs=0.417, P=0.025) and negatively with serum BAFF levels (rs=-0.486, P=0.008) at baseline. Serum visfatin levels were significantly higher in patients with RA compared with healthy controls (P=0.026), and significantly decreased (P=0.010), while BAFF increased (P<0.001), and both proteins became negatively correlated following treatment with rituximab (rs=-0.438, P=0.017). Visfatin levels did not correlate with the disease activity, but lack of change in the serum visfatin levels between baseline and week 16 predicted worsening disease activity between weeks 16 and 24 (rs=0.452, P=0.014). CONCLUSION: In patients with active RA, serum visfatin levels are related to the number of B cells rather than to disease activity and decrease in response to treatment with rituximab. Further studies are necessary to show if visfatin is a marker with predictive value for deterioration of RA.