Correlation of serum protein biomarkers with disease activity in psoriatic arthritis.

Objective: To assess the correlation of serum protein biomarkers with disease activity across different domains of psoriatic arthritis (PsA).Material and methods: A cross-sectional cohort of 45 adult patients with PsA fulfilling the classification for psoriatic arthritis (CASPAR) criteria was recruited from University of California San Diego (UCSD) Arthritis Clinics. Clinical data and serum samples were collected and serum was analyzed for protein biomarkers hypothesized to be relevant to disease activity in PsA. Correlations were evaluated for clinical disease activity measures across disease domains.Results: Biomarkers with the highest correlation to the composite indices and disease domains were SAA, IL-6, YKL-40, and ICAM-1. In addition, several biomarkers were moderately correlated with individual composite indices and/or disease domains. Low or no correlation was observed with some biomarkers, e.g. MMP-3, MMP-1, EGF, VEGF, and IL-6R. In contrast, the correlation of all biomarkers with certain disease domains was low; specifically, pain, percent body surface area of psoriasis, and patient global assessment. The multi-biomarker disease activity score (MBDA) developed for rheumatoid arthritis (RA) showed high correlations with most composite indices and some disease domains in PsA.Conclusions: These data suggest biomarker analysis can reflect disease activity across disease domains in PsA. Certain domains would likely benefit from the evaluation of additional biomarkers.

Predictive value of a multi-biomarker disease activity score for clinical remission and radiographic progression in patients with early rheumatoid arthritis: a post-hoc study of the OPERA trial.

OBJECTIVES: Measurement of serum biomarkers at disease onset may improve prediction of disease course in patients with early rheumatoid arthritis (RA). We evaluated the multi-biomarker disease activity (MBDA) score and early changes in MBDA score for prediction of 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) remission and radiographic progression in the double-blinded OPERA trial. METHOD: Treatment-naïve RA patients (N = 180) with moderate or high DAS28 were randomized to methotrexate (MTX) + adalimumab (n = 89) or MTX + placebo (n = 91) in combination with glucocorticoid injection into swollen joints. X-rays of hands and feet were evaluated at months 0 and 12 (n = 164) by the total Sharp van der Heijde score (TSS). The smallest detectable change (1.8 TSS units) defined radiographic progression (∆TSS ≥ 2). Clinical remission (DAS28-CRP < 2.6) was assessed at baseline and 6 months. MBDA score was determined at 0 and 3 months and tested in a multivariable logistic regression model for predicting DAS28 remission at 6 months and radiographic progression at 1 year. RESULTS: Baseline MBDA score was independently associated with radiographic progression at 1 year [odds ratio (OR) = 1.03/unit, 95% confidence interval (CI) = 1.01-1.06], and changes in MBDA score from baseline to 3 months with clinical remission at 6 months [OR = 0.98/unit, 95% CI 0.96-1.00). In anti-cyclic citrullinated peptide antibody (anti-CCP)-positive patients, 35 of 89 with high MBDA score (> 44) showed radiographic progression (PPV = 39%), compared with 0 of 15 patients (NPV = 100%) with low/moderate MBDA score (≤ 44) (p = 0.003). CONCLUSION: Early changes in MBDA score were associated with clinical remission based on DAS28-CRP at 6 months. In anti-CCP-positive patients, a non-high baseline MBDA score (≤ 44) had a clinical value by predicting very low risk of radiographic progression at 12 months.

Investigation of a multi-biomarker disease activity score in rheumatoid arthritis by comparison with magnetic resonance imaging, computed tomography, ultrasonography, and radiography parameters of inflammation and damage.

OBJECTIVES: To investigate the multi-biomarker disease activity (MBDA) score by comparison with imaging findings in an investigator-initiated rheumatoid arthritis (RA) trial (HURRAH trial, NCT00696059). METHOD: Fifty-two patients with established RA initiated adalimumab treatment and had magnetic resonance imaging (MRI), ultrasonography (US), computed tomography (CT), and radiography performed at weeks 0, 26, and 52. Serum samples were analysed using MBDA score assays and associations between clinical measures, MBDA score, and imaging findings were investigated. RESULTS: The MBDA score correlated significantly with MRI synovitis (rho = 0.65, p < 0.001), MRI bone marrow oedema (rho = 0.36, p = 0.044), and US power Doppler (PD) score at week 26 (rho = 0.35, p = 0.039) but not at week 0 or week 52. In the 15 patients who had achieved a Disease Activity Score based on C-reactive protein (DAS28-CRP) < 2.6 at week 26, MRI and/or US detected subclinical inflammation and 13 (87%) had a moderate/high MBDA score. For the cohort with available data, none of the four patients in MBDA remission (score ≤ 25) at week 26 had progression of imaging damage from baseline to week 52 whereas progression was observed in three out of nine (33%) and seven out of 21 (33%) patients with moderate (30-44) and high (> 44) MBDA scores, respectively. CONCLUSIONS: In this cohort, the MBDA score correlated poorly with MRI/US inflammation. However, the MBDA score and MRI/US were generally concordant in showing signs of inflammation in most patients in clinical remission during anti-tumour necrosis factor (anti-TNF) therapy. MBDA scores were elevated in all patients with structural damage progression.

Recent contributions to transplantation at the University of Cincinnati.

1. Clinical investigations at the University of Cincinnati have focused primarily on infection control, methods to increase donor-specific unresponsiveness, improvement in immunosuppression, donor maintenance and evaluation, posttransplant monitoring, and reduced-size livers for children. 2. Donor specific unresponsiveness (DSU) can be achieved frequently in recipients of both cadaver donor and living related donor kidneys by giving a single donor specific transfusion and CsA only 24 hours preoperatively with continuing triple immunosuppressive therapy. 3. Prednisone can be withdrawn from almost all patients with no rejection by 1 year with significant improvement in blood pressure, daily insulin requirement in diabetics, total blood cholesterol, and low density lipoproteins (LDL). 4. Oral ketoconazole 200 mg/day can be used safely to block the hepatic metabolism of CsA and reduce the amount of CsA administered by an average of 77-88%. This is of great economic consequence to lower income patients and patients with poor drug absorption. 5. Eighteen patients with SLE who received 23 kidney transplantations had an increase in graft loss in the first 6 months but the rate of graft loss after 6 months was almost identical to other ESRD patients. 6. The Cincinnati Transplant Tumor Registry has data on about 8,000 patients. Except for those with CNS tumors, patients with active cancers should not be used as donors. However, donors with previous curative procedures should not be excluded automatically. Cancers arising in immunosuppressed transplant recipients that have a higher incidence than the general population (expressed as percentage of treated cancers) are: lymphomas (22% vs 5%), lip cancers (7% vs 0.3%), Kaposi's sarcoma (6% vs less than 0.1%), vulva and perineal cancers (4% vs 0.6%), hepatobiliary cancers (2.5% vs 1.0%) and sarcomas (1.8% vs 0.5%). Other cancers have about the same-distribution. 7. Immunologic monitoring during OKT3 therapy is particularly useful in re-treatment and treatment of pediatric liver patients when increased doses of the drug may be necessary. 8. The MEGX test has been found to be a major predictor of primary non-function of the transplanted liver, and it is also useful in predicting the risks of dying from liver disease. 9. Reduced-size livers have been used in 37 patients, representing almost half of all pediatric liver transplants. Survival with reduced-size grafts (91% at 1 year) compared favorably with survival of whole organs (79% at 1 year). The benefit is particularly dramatic in infants with biliary atresia (100% 1-year graft survival in 24 patients, median age 11 months).(ABSTRACT TRUNCATED AT 400 WORDS)