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Objective To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). Methods In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. Results Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline −0.43 versus −0.07; P <0.001), decreased the overall incidence of gout flares (29.3% versus 41.4%; P < 0.05), and improved serum UA control (62.8% versus 5.7%; P < 0.001). No major safety concerns were reported. Conclusion Urate-lowering therapy with febuxostat improved magnetic resonance imaging-determined synovitis and reduced the incidence of gout flares in subjects with early gout. [ABSTRACT FROM AUTHOR]

Objective To test the hypothesis that remission of Behçet's disease ( BD) in patients with severe vital organ involvement is maintained after withdrawal of successful anti-tumor necrosis factor (anti- TNF) treatment. Methods This single-center, retrospective, longitudinal outcomes study focused on consecutive patients with disease refractory to treatment with conventional immunosuppressant agents who responded to add-on long-term anti- TNF treatment that was subsequently discontinued. The end point was the proportion of patients remaining in complete remission for at least 3 years after withdrawal of anti- TNF treatment. Results In our BD cohort comprising 87 patients, 29 were eligible for analysis. All of these patients had disease that was refractory to conventional immunosuppressive therapy and had received successful anti- TNF treatment for a median of 2 years (interquartile range [ IQR] 1.1-2.0) before treatment discontinuation. Of these patients, 12 (41%) achieved the study end point. The remaining 17 patients experienced a relapse within 1 year ( IQR 0.6-1.5) after discontinuation. Re-treatment with anti- TNF was safe and effective in 14 (82%) of 17 patients; so far, 4 of these patients also achieved the study end point. Overall, 16 patients have remained in complete remission (median 6.5 years [ IQR 5.5-8]). Ten of these patients are in drug-free remission (treated with anti- TNF agents, mainly for sight-threatening disease), and 6 are in azathioprine-maintained remission (treated with anti- TNF agents for ocular, intestinal, or central nervous system involvement). Notably, patients in drug-free remission were significantly younger and had a significantly shorter duration of BD when anti- TNF treatment was initiated compared to patients receiving azathioprine maintenance treatment. Conclusion Drug-free, long-term remission after withdrawal of successful anti- TNF treatment is feasible in patients with severe BD. Because an anti- TNF agent-induced 'cure' cannot be differentiated from spontaneous remission by natural history, prospective studies should examine whether anti- TNF agents should be used as first-line treatment for the induction of remission in every patient with vital organ involvement. [ABSTRACT FROM AUTHOR]

Objective To estimate the proportion of patients with axial spondyloarthritis (SpA) in a UK national biologics registry who met criteria for fibromyalgia ( FM), and to delineate the characteristics of these patients. Methods Two cohorts of patients are prospectively recruited from across 83 centers in the UK for the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis ( BSRBR- AS). All patients are required to meet Assessment of SpondyloArthritis international Society ( ASAS) criteria for axial SpA. Patients are either newly starting biologic therapy (biologics cohort) or are naive to treatment with biologic agents (non-biologics cohort) at the time of recruitment, and all patients are followed up prospectively. At recruitment and follow-up, clinical information and measurements are recorded while patients complete the 2011 research criteria for FM and assessments of the level of disease activity and work impact. Results Of the patients registered in the BSRBR- AS, 1,504 (68% male) were eligible for the current analysis, of whom 311 (20.7%) met the 2011 research criteria for FM. Prevalence of FM was similar between patients who fulfilled the modified New York criteria for AS (19.7%) and those who fulfilled ASAS imaging criteria but not the modified New York criteria (25.2%); however, among those who fulfilled only the ASAS clinical criteria, the prevalence of FM was lower (9.5%). Patients who met FM criteria reported significantly worse disease activity, function, global severity scores, and quality of life, and were more likely to have moderate or severe levels of mood disorder and clinically important fatigue. Patients who met FM criteria reported experiencing work impairment around half their working time. Meeting FM criteria was not related to elevated C-reactive protein levels or most extraspinal manifestations, but was associated with a higher likelihood of having received biologic therapy. Conclusion Developing management approaches that would address the significant unmet clinical needs of the 1 in 5 patients with axial SpA who meet criteria for FM should be a research priority. [ABSTRACT FROM AUTHOR]

Objective Serum anti-citrullinated peptide antibodies ( ACPAs) may be present before the development of rheumatoid arthritis ( RA) and may be predictive of more severe, erosive disease. This study was undertaken to examine the synovial tissue immunophenotype according to ACPA status in patients with RA, as well as the response to treatment and erosion status. Methods Consecutive RA patients were prospectively recruited and underwent clinical and serologic assessments before and after treatment. Radiologic assessment was performed at the time of clinical follow-up. Synovial tissue was immunostained for specific markers of B cells ( CD19), T cells ( CD3, CD4, and CD8), macrophages ( CD68), and blood vessels (factor VIII). Serum CXCL13 levels were quantified by enzyme-linked immunosorbent assay. Synovial tissue sections were analyzed for immunophenotype according to ACPA status, using a validated semiquantitative scoring method, and also analyzed for the presence of lymphoid aggregates. Response to treatment with nonbiologic or biologic disease-modifying antirheumatic drugs was assessed using the European League Against Rheumatism ( EULAR) response criteria. Results In total, 123 subjects (78 ACPA+) were included. Compared to ACPA- RA patients, synovium from ACPA+ RA patients was characterized by significantly higher levels of CD19+ B cells and CD3+ and CD8+ T cells (each P < 0.05), and CD19+ B cell levels were significantly higher in patients who were naive to treatment. The CD19+ B cell infiltrate level was higher in patients with erosions at follow-up ( P = 0.0128). Levels of lymphoid aggregates of CD19+ B cells were significantly higher in ACPA+ patients ( P < 0.05), and this was associated with increased serum CXCL13 levels. The EULAR response was significantly associated with the level of CD3+ T cell infiltrates ( P < 0.05), while CD68+ macrophage and CD8+ T cell levels were predictive of the response to tumor necrosis factor inhibitors ( P < 0.05). Conclusion The results of this prospective study demonstrate that the levels of synovial B cell infiltrates and lymphoid aggregates were significantly higher in ACPA+ RA patients, especially those who were naive to treatment. In addition, ACPA+ subjects developed more erosions during progression of the disease and had higher serum levels of CXCL13. The EULAR response to therapy in ACPA+ RA patients was associated with increased levels of T cell and macrophage markers. [ABSTRACT FROM AUTHOR]

Objective There are few clinical predictors of the progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD). The purpose of this study was to examine the predictive significance of key cytokines for long-term progression of ILD and survival in 2 independent cohorts of patients with early SSc. Methods Plasma levels of 11 Th1/Th2 cytokines (interleukin-1β [IL-1β], IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, tumor necrosis factor, CCL2, interferon-inducible T cell α chemoattractant, and interferon-γ-inducible 10-kd protein) were measured in 266 patients with early SSc in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) discovery cohort. Levels of CCL2, IL-10, and IL-6 were measured in 171 patients with early SSc in the Canadian Scleroderma Research Group (CSRG) replication cohort. The primary outcome measure was a decline in the forced vital capacity percent predicted (FVC%) value over time. A joint analysis of longitudinal FVC% values and survival was performed. Results After adjustment for age, sex, and ethnicity, CCL2 and IL-10 were found to be significant predictors of ILD progression in the discovery cohort. Higher CCL2 levels predicted a faster decline in FVC% values (b = −0.57, P = 0.032), while higher IL-10 levels predicted a slower decline (b = 0.26, P = 0.01). A higher CCL2 value was also predictive of poorer survival (hazard ratio 1.76, P = 0.030). In the CSRG replication cohort, higher CCL2 levels predicted a faster decline in FVC% values (b = −0.58, P = 0.038), but neither IL-10 nor IL-6 had predictive significance. A higher CCL2 level also predicted poorer survival (hazard ratio 3.89, P = 0.037). Conclusion Higher CCL2 levels in the circulation were predictive of ILD progression and poorer survival in patients with early SSc, findings that support the notion that CCL2 has a role as a biomarker and potential therapeutic target. [ABSTRACT FROM AUTHOR]

Objective To assess the therapeutic efficacy of local injections of botulinum toxin type A (Btx-A) in improving blood flow to the hands of patients with Raynaud's phenomenon (RP) secondary to scleroderma. Methods In this randomized, double-blind, placebo-controlled clinical trial, patients with scleroderma-associated RP received Btx-A (50 units in 2.5 ml sterile saline) in one randomly selected hand and sterile saline (2.5 ml) in the opposite hand. Follow-up at 1 and 4 months postinjection included laser Doppler imaging of hands, patient-reported outcomes, and physical examination. We compared outcomes using paired t-tests and population-average generalized models with generalized estimating equations. Results Of 40 patients enrolled, 25 had limited scleroderma and 15 had diffuse scleroderma. From baseline to 1-month follow-up, there was a greater reduction in average blood flow in Btx-A-treated hands compared to placebo-treated hands. The model estimated that this difference was statistically significant (average difference −30.08 flux units [95% confidence interval −56.19, −3.98], P for interaction = 0.024). This difference was mainly influenced by patients with longstanding RP and diffuse scleroderma. Change in blood flow at 4-month follow-up was not significantly different between groups. Clinical measures (QuickDASH, McCabe Cold Sensitivity Score, pain on a visual analog scale, and Raynaud's Condition Score) improved slightly for Btx-A-treated hands. Conclusion Our laboratory-based laser Doppler imaging flow data do not support using Btx-A to treat RP in all scleroderma patients. The secondary clinical outcomes suggest some positive effect, but its clinical meaningfulness is questionable. The role of Btx-A in treating RP should be further studied with more homogeneous patient populations and in unique clinical situations such as acute digital ischemia. [ABSTRACT FROM AUTHOR]