Adjustment of the multi-biomarker disease activity score to account for age, sex and adiposity in patients with rheumatoid arthritis.

OBJECTIVE: To develop and evaluate an adjusted score for the multi-biomarker disease activity (MBDA) test to account for the effects of age, sex and adiposity in patients with RA. METHODS: Two models were developed to adjust MBDA score for age, sex and adiposity, using either serum leptin concentration or BMI as proxies for adiposity. Two cohorts were studied. A cohort of 325 781 RA patients who had undergone commercial MBDA testing and had data for age, sex and serum leptin concentration was used for both models. A cohort of 1411 patients from five studies/registries with BMI data was used only for the BMI-adjusted MBDA score. Univariate and multivariate linear regression analyses evaluated the adjusted MBDA scores and conventional clinical measures as predictors of radiographic progression, assessed in terms of modified total Sharp score (ΔmTSS). RESULTS: Two models were developed, based on findings that MBDA score was higher in females than males and increased with age, leptin concentration and BMI. In pairwise regression analyses, the leptin-adjusted (P = 0.00066) and BMI-adjusted (P = 0.0027) MBDA scores were significant independent predictors of ΔmTSS after adjusting for DAS28-CRP, whereas DAS28-CRP was not, after adjusting for leptin-adjusted (P = 0.74) or BMI-adjusted (P = 0.87) MBDA score. Moreover, the leptin-adjusted MBDA score was a significant predictor of ΔmTSS after adjusting for the BMI-adjusted MBDA score (P = 0.025) or the original MBDA score (0.027), whereas the opposite was not true. CONCLUSION: Leptin-adjusted MBDA score significantly adds information to DAS28-CRP and the original MBDA score in predicting radiographic progression. It may offer improved clinical utility for personalized management of RA.

The safety of low-dose glucocorticoids in rheumatic diseases: results from observational studies.

Glucocorticoids (GC) remain the most commonly used agents for managing inflammatory rheumatic diseases. The adverse effects (AEs) associated with high-dose GCs are well established, but there is a widespread misconception that AEs of high-dose GC therapy (>30 mg of prednisone or equivalent daily) are similar in low-dose therapy (≤7.5 mg of prednisone equivalent a day). Although high-quality evidence on AEs of low-dose GC therapy is still incomplete, risks and safety of low-dose GC therapy in rheumatic diseases are reviewed based on current evidence by category, including musculoskeletal, cardiovascular, infectious, gastrointestinal, neuropsychiatric, endocrine and metabolic, dermatologic, and ophthalmologic AEs. Recommendations concerning monitoring AEs with low-dose GC therapy are provided for each category of AEs on the basis of our literature review and clinical experience. There is emerging evidence that low-dose GCs are associated with a much lower level of AEs, which would allow their use over long periods in patients with rheumatic disease who gain clinical effectiveness and well-being from their use. Nonetheless, knowledge and understanding of AEs from low-dose GCs is vital to maximize benefits and minimize risks to patients.

Induction therapy with combination TNF inhibitor and methotrexate in early rheumatoid arthritis.

With the introduction of more objective disease activity measures and the development of biological therapies, there were dramatic changes in the treatment of rheumatoid arthritis (RA). The combination therapy with tumor necrosis factor (TNF) inhibitor and methotrexate (MTX) has unprecedentedly improved prognosis and outcomes, and very low disease activity or remission has been achievable goal in RA. Although the concept of remission induction and maintenance was first discussed in longstanding RA patients, several clinical trials have demonstrated that there is a therapeutic window of opportunity, and early effective control of inflammation in early RA could lead to less joint damage and better long-term outcomes. Emerging evidence suggests that early combination therapy with TNF inhibitor and MTX leads to rapid clinical remission and thereby improved quality of life. Furthermore, remission status may be sustained in some patients even if a TNF inhibitor is discontinued after sustained remission in early RA patients. While there are many potential benefits of early remission induction therapy with the combination of a TNF inhibitor and MTX, the best therapeutic regimen and strategy for remission induction and maintenance in early RA remain controversial. There are no data to decide a priori when and in whom TNF blocker drugs are indicated in early disease-modifying anti-rheumatic drug (DMARD)-naïve RA.

Evaluation of macrophage activation syndrome in hospitalised patients with Kikuchi-Fujimoto disease based on the 2016 EULAR/ACR/PRINTO classification criteria.

BACKGROUND: To evaluate the impact of macrophage activation syndrome (MAS) on clinical features in patients with Kikuchi-Fujimoto disease (KFD) and to compare the features of MAS in KFD with those of adult-onset Still's disease (AOSD) and systemic lupus erythematosus (SLE). METHODS: The medical records of febrile patients hospitalised with KFD between November 2005 and April 2017 were reviewed. Patients fulfilling the 2016 classification criteria for MAS were classified as having MAS. Clinical and laboratory features of patients with KFD with and without MAS were evaluated. Poor hospitalisation outcomes were defined as intensive care unit admission or in-hospital mortality. The treatment outcomes of MAS in KFD, AOSD, and SLE were also compared. RESULTS: Among 78 patients hospitalised with KFD, 24 (30.8%) patients had MAS during admission. Patients with KFD and MAS more frequently required glucocorticoid treatment (66.7% vs 40.7%, p = 0.036) and had longer hospital stays than patients with KFD without MAS (12.5 vs 8.5 days, p<0.001). In addition, patients with MAS had worse hospitalisation outcomes than patients without MAS (29.2% vs. 0.0%, p<0.001). Among patients with MAS in KFD, AOSD, and SLE, the number of patients requiring glucocorticoid treatment after 3 months was significantly lower among patients with MAS and KFD (KFD 33.3%, AOSD 88.9%, SLE 100%, p<0.001). CONCLUSIONS: The presence of MAS in KFD was associated with adverse clinical outcomes including higher steroid usage and worse hospitalisation outcomes. However, compared to those with AOSD and SLE, patients with MAS and KFD were less likely to require long-term glucocorticoid treatment.

Differential response of serum amyloid A to different therapies in early rheumatoid arthritis and its potential value as a disease activity biomarker.

BACKGROUND: The aim was to compare the effect of etanercept (ETN) and conventional synthetic disease-modifying anti-rheumatic drug (DMARD) therapy on serum amyloid A (SAA) levels and to determine whether SAA reflects rheumatoid arthritis (RA) disease activity better than C-reactive protein (CRP). METHODS: We measured SAA and CRP at baseline, 24, 48, and 102 week follow-up visits in 594 patients participating in the Treatment of early RA (TEAR) study. We used Spearman correlation coefficients (rho) to evaluate the relationship between SAA and CRP and mixed effects models to determine whether ETN and methotrexate (MTX) treatment compared to triple DMARD therapy differentially lowered SAA. Akaike information criteria (AIC) were used to determine model fits. RESULTS: SAA levels were only moderately correlated with CRP levels (rho = 0.58, p < 0.0001). There were significant differences in SAA by both visit (p = 0.0197) and treatment arm (p = 0.0130). RA patients treated with ETN plus MTX had a larger reduction in SAA than patients treated with traditional DMARD therapy. Similar results were found for serum CRP by visit (p = 0.0254) and by treatment (p < 0.0001), with a more pronounced difference than for SAA. Across all patients and time points, models of the disease activity score of 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) using SAA levels were better than models using CRP; the ΔAIC between the SAA and CRP models was 305. CONCLUSIONS: SAA may be a better biomarker of RA disease activity than CRP, especially during treatment with tumor necrosis factor (TNF) antagonists. This warrants additional studies in other cohorts of patients on treatment for RA. TRIAL REGISTRATION: (ClinicalTrials.gov identifier: NCT00259610 , Date of registration: 28 November 2005).

The METEOR trial: no rush to repair a torn meniscus.

It is uncertain whether arthroscopic partial meniscectomy is better than physical therapy in patients who have a symptomatic torn meniscus on top of osteoarthritis of the knee. The Meniscal Repair in Osteoarthritis Research (METEOR) trial concluded that physical therapy is acceptable at first, and that surgery is not routinely needed. In patients assigned to physical therapy who eventually needed surgery, the delay resulting from a trial of conservative management did not impair outcomes at 12 months from the initial presentation. Here, we analyze the background, design, findings, and clinical implications of the METEOR trial.

Increased vitamin D is associated with decline of naïve, but accumulation of effector, CD8 T cells during early aging.

Given the protective roles of 25-hydroxyvitamin D (25[OH]D or vitamin D) in musculoskeletal health and the potential beneficial effects of vitamin D supplementation in reducing the risk of various chronic diseases, intensive repletion of vitamin D has been widely advocated. Of note, CD8 T cells have the highest levels of the vitamin D receptor compared with other major immune cells. The effects of vitamin D on CD8 T cells during aging, however, remain unclear. This study determined the relationship between vitamin D levels and CD8 T-cell status in 34 healthy female subjects (all >60 years old). The CD8 T cell phenotype was defined by the surface expression of CD28 and CD95. The low-25(OH)D serum groups (≤30 ng/ml) had higher percentages of CD28+CD95-CD8+ (naïve) T cells and lower percentages of CD28+CD95+CD8+ (effector) T cells. By contrast, subjects with high levels of 25(OH)D had very low percentages of naïve CD8 T cells but very high percentages of effector CD8 T cells. There was a significant inverse correlation between 25(OH)D levels and the frequency of naïve CD8 T cells. The results show that higher levels of vitamin D are correlated with decreased frequencies of naïve CD8 T cells during early aging, suggesting that higher levels of 25(OH)D accelerate CD8 T-cell senescence. These results warrant the further evaluation of the effects of vitamin D supplementation in immune aging.