Objective Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision-making. We validated a recently-developed multi-biomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts. Methods Serum samples were obtained from the InFoRM, BRASS, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a pre-specified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson correlations and area under the receiver operator characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6–12 weeks after initiation of anti-TNF or methotrexate treatment were evaluated by AUROC. Results The MBDA score was significantly associated with DAS28-CRP in both seropositive (AUROC=0.77; P<0.001) and seronegative patients (AUROC=0.70; P<0.001). In subgroups based on age, sex, body-mass index, and treatment, the MBDA score was associated with DAS28-CRP (P<0.05) in all seropositive and most seronegative subgroups. Changes in MBDA score at 6–12 weeks could discriminate both ACR50 responses (P=0.03) and DAS28-CRP improvement (P=0.002). Changes in MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P=0.02). Conclusion Our findings establish the criterion and discriminant validity of a novel multi-biomarker test as an objective measure of RA disease activity to aid in the management of RA patients.

To determine whether reticuloendothelial-system immunospecific Fc-receptor function is abnormal in patients with systemic lupus erythematosus, we studied the clearance of IgG-sensitized 51Cr-labeled erythrocytes by these splenic macrophage membrane receptors in 15 untreated patients. Fc-specific clearance rates were strikingly abnormal in 13 of 15 patients (half-times ranging from 80 to 2256 minutes, P less than 0.001 as compared to controls). Abnormal clearances correlated with immune-complex levels (as measured by the C1q-binding assay) and with disease activity. C1q-binding activity and anti-DNA titers also correlated with disease activity. The correlations of C3, C4, CH50 and factor B with abnormal clearance and disease activity were weaker or nonexistent. The significant correlations among clearance, disease activity and C1q-binding activity suggest that the defect in Fc-receptor function may lead to the prolonged circulation of immune complexes, thereby contributing to tissue deposition and damage.

Gout is a major health problem in the United States; it affects 8.3 million people, which is approximately 4% of the adult population. Gout is most often diagnosed and managed in primary care physician practices. Primary care physicians have a significant opportunity to diagnose and manage patients with gout and improve patient outcomes. Following publication of the 2006 European League Against Rheumatism (EULAR) gout guidelines, significant evidence on gout has accumulated and new treatments for patients with gout have become available. It is the objective of these 2011 recommendations for the diagnosis and management of gout and hyperuricemia to update the 2006 EULAR guidelines, paying special attention to the needs of primary care physicians, who manage most patients with gout. The revised 2011 recommendations are based on the Grading of Recommendations Assessment, Development, and Evaluation approach as an evidence-based strategy for rating quality of evidence and grading strength of recommendation in clinical practice. A total of 26 key recommendations for diagnosis (n = 10) and management (n = 16) were evaluated. Presence of tophus (proven or suspected) and response to colchicine had the highest clinical diagnostic value (likelihood ratio [LR], 15.56 [95% CI, 2.11-114.71] and LR, 4.33 [95% CI, 1.16-16.16], respectively). The key aspect of effective management of an acute gout attack is initiation of treatment within hours of onset of first symptoms. Low-dose colchicine is better tolerated than and is as effective as high-dose colchicine (number needed to treat [NNT], 5 [95% CI, 3-13] and NNT, 6 [95% CI, 3-72], respectively). For urate-lowering therapy, allopurinol in combination with probenecid was shown to be more effective than either agent alone (effect size [ES], 5.51 for combination; ES, 4.46 for probenecid; and ES, 2.80 for allopurinol). Febuxostat, also a xanthine oxidase inhibitor, has a slightly different mechanism of action and can be prescribed at unchanged doses for patients with mild-to-moderate renal or hepatic impairment. Febuxostat 40 mg versus 80 mg (NNT, 6 [95% CI, 4-11]) and 120 mg (NNT, 6 [95% CI, 3-26]) both demonstrated long-term efficacy. The target of urate-lowering therapy should be a serum uric acid level of ≤ 6 mg/dL. For patients with refractory and tophaceous gout, intravenous pegloticase is a new treatment option.

We investigated the opsonic requirements for intravascular clearance of pneumococci in guinea pigs and of sensitized erythrocytes in human beings after splenectomy. The impaired clearance of injected pneumococci in splenectomized guinea pigs was corrected by immunization. This improvement in clearance was due to increased hepatic sequestration of organisms. There was a significant delay in antibody-mediated clearance of autologous erythrocytes sensitized with IgG (P < 0.001), although the rate of complement-mediated clearance in splenectomized patients was normal. A fourfold increase in sensitizing antibody resulted in a significant improvement in clearance that was due to increased hepatic sequestration (P < 0.005). One patient who had an intact spleen and who had previously received Thorotrast (thorium oxide) had impaired antibody-mediated clearance despite increased sensitization. These observations suggest that, after splenectomy the remaining macrophages of the reticuloendothelial system require increased amounts of antibody to mediate efficient intravascular clearance of opsonized particles.