ObjectivesTraditional cardiovascular risk calculators such as the Framingham Risk Score (FRS) have been shown to underestimate risk in patients with SLE. The QRISK3 calculator is unique in including SLE and corticosteroid use as risk factors. This study aims to assess the validity of QRISK3 compared with other cardiovascular risk models in a cohort of patients with SLE in the USA.MethodsWe studied a prospective cohort of 366 adult patients with SLE without history of any cardiovascular event and followed them for 10 years. We compared the diagnostic performance of QRISK3 with FRS, modified FRS, Atherosclerotic Cardiovascular Disease (ASCVD), and Predictors of Risk for Elevated Flares, Damage Progression and Increased Cardiovascular Disease in Patients with SLE (PREDICTS).ResultsSixty-four of the 366 patients (17.4%) experienced at least one cardiovascular event during the 10-year follow-up period. Of these patients 45% had a QRISK3 score >10%, whereas 20.5% of patients who did not have an event had a QRISK3 score >10% (p<0.001). The corresponding numbers for FRS, modified FRS, ASCVD and PREDICTS were 11.0% vs 7.2% (p=ns), 40.6% vs 28.0% (p=0.05), 12.2% vs 5.9% (p=ns), and 77% vs 32.1% (p<0.001), respectively. The areas under the receiver operating characteristic curve using QRISK3 >10% and high-risk PREDICTS were both larger than those using ASCVD >10%, FRS >10% and modified FRS >10%.ConclusionsBoth QRISK3 and PREDICTS demonstrated better performance in predicting risk of cardiovascular disease in this cohort of patients with SLE compared with FRS, modified FRS and ASCVD.

Objective Interstitial lung disease (ILD) is a major cause of morbidity and mortality in connective tissue diseases (CTDs). We aimed to assess the effect of rituximab ± mycophenolate mofetil (MMF) compared with MMF on pulmonary function and prednisone dosage in patients with CTD‐related ILD (CTD‐ILD). Methods This retrospective study included 83 patients from Stanford and Centre Hospitalier de l’Universite de Montreal. Fifteen patients received rituximab ± MMF (rituximab group), and 68 patients received MMF only (control group). Results Median ILD duration at the start of treatment was longer in the rituximab group at 47 months (range: 4‐170) versus 6.5 months (range: 0‐164) in controls. Forced vital capacity (FVC) decreased by 3.0% (range: 11%‐21%) after treatment in the rituximab group, whereas it increased by 2.0% (range: 14%‐25%) in the control group (p = 0.025). Diffusing capacity of carbon monoxide (DLCO) decreased by 3.0% (range: 10%‐12%) after treatment in the rituximab group, whereas it increased by 4.5% (range: 30%‐36%) in the control group (p = 0.046). Mixed model analysis controlling for ILD duration, baseline DLCO, systemic sclerosis, pulmonary hypertension, and prednisone use showed no significant difference in FVC or DLCO between groups at 6 months or 1 year. The average daily prednisone dose score decreased after treatment in the rituximab group, whereas it remained unchanged in the control group (p = 0.017). Conclusion Rituximab ± MMF did not significantly change pulmonary function compared with MMF alone, but it did result in a relative decrease in average daily prednisone dose in a population with recalcitrant CTD‐ILD.

Human epididymis protein 4 (HE4) is a whey acidic four-disulfide core protein. Serum HE4 has been shown to be a promising biomarker for epithelial ovarian cancer (EOC) with manual HE4 EIA assays. The ARCHITECT system is one of the major automated formats for cancer immunodiagnostics. This abstract describes the clinical performance of an investigational ARCHITECT HE4 assay in the measurement of serum HE4 from longitudinal samples of subjects with EOC and single-point samples from healthy subjects, and subjects with malignancy, benign diseases, EOC or other malignant diseases. PROCEDURES: The ARCHITECT HE4 Assay is a paramagnetic microparticle chemiluminescent assay adopting the sensitive CHEMIFLEX® technology. Single-point and longitudinal serum samples were tested with an investigational ARCHITECT HE4 Assay reagent lot on the ARCHITECT i2000SR. Single-point sera were collected from healthy subjects (N = 400), subjects with pregnancy (N = 50) and benign disease (N = 612), and subjects which were diagnosed with EOC (N = 314) and other cancers (N = 250) including endometrial, breast, gastrointestinal, lung, and bladder cancer. Longitudinal sera (N = 506), including initial time point and follow-up visits (average = 5.7 per subject), were collected from subjects (N = 76) which were diagnosed with EOC. All of the single-point and longitudinal samples were handled in accordance with IRB-approved and GCP-compliant protocols. RESULTS: Using an ARCHITECT HE4 cut-off value of &gt;140 pmol/L, the percent distributions of ARCHITECT HE4 by cohort are: 3% of healthy subjects, 0% with pregnancy, 7.2% of subjects with benign diseases, 53.5% with EOC and 28.4% with other cancers. Using the upper 95% point of the distribution of the HE4 ratio at 14% to categorize the successive HE4 readings into those that were and were not significantly elevated for the longitudinal samples, the sensitivity, specificity and positive predictive value of HE4 elevation versus disease progression were 53.4% (95% CI: 44.1%-62.5%), 78.8% (95% CI: 74.7% - 82.4%) and 43.2% (95% CI: 32.9% - 54.1%) respectively. The total concordance between HE4 elevation and disease progression was 73%. Receiver Operator Characteristic analysis showed an area under the curve of 0.685 (SE = 0.033) for the diagnosis of progression from the ratio of successive HE4 readings. When comparing the change of the HE4 ratio with the diagnostic response to therapy, a decrease in HE4 reflected response to therapy with a sensitivity of 82% and a specificity of 53%. CONCLUSIONS: The study with single-point samples has shown the utility of ARCHITECT HE4 values as a serum biomarker for EOC. The longitudinal increase of ARCHITECT HE4 values in sera seemed to be effective in recognizing the progression of EOC. The longitudinal decrease of ARCHITECT HE4 values in sera seemed to correlate with the response of EOC subjects to therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4653.

Methotrexate (MTX) is a cancer therapeutic drug for leukemia, osteosarcoma, non-Hodgkin's lymphoma and others. MTX levels in blood are monitored in patients to avoid toxic effects caused by the excessive dosage of this drug, and to determine when to intervene with the counter-acting ‘rescue’ therapy. An assay for serum and plasma MTX measurement on ARCHITECT i System (ARCHITECT Methotrexate) is being developed and the analytical feasibility of this assay is presented. METHODS: The ARCHITECT Methotrexate is a competitive immunoassay. First, the instrument mixes and incubates a sample (calibrators, controls, sera or plasma) with anti-methotrexate antibody-coated magnetic microparticles, biotinylated anti-methotrexate antibody and acridinium-conjugated MTX. Then, the instrument washes the microparticles and adds pre-trigger and trigger solutions to initiate the chemiluminescence reaction. Signals obtained as relative luminescent units are inversely proportional to the amount of MTX in the sample. RESULTS: The limit of quantitation was ≤ 0.040 µmol/L MTX. The 20-day imprecision study showed a total CV ≤ 7.1% within the range of 0.056 to 1705.433 µmol/L MTX with 6 controls and 5 panels on 4 instruments using 3 lots of reagents (n = 80). Dilution linearity showed the deviations from linearity were -4.1% to 7.2% within the range of 1.881 to 0.012 µmol/L MTX. Spike recovery revealed a mean recovery of 92% - 94% for samples at 0.045, 0.909 and 9.090 µmol/L of MTX. In the interference studies, the average levels of MTX in the individual interfering substance-spiked samples (10 endogenous substances including human anti-mouse antibody and rheumatoid factor, and 21 therapeutic drugs) were within 90% - 110% of that in the unspiked control samples. Method comparison of ARCHITECT Methotrexate to TDx/TDxFLx Methotrexate II (TDx) generated a Passing Bablok correlation as [ARCHITECT] = 0.00 + 1.01 [TDx] for samples within the range of 0.040 to 1.415 µmol/L (n = 92) and [ARCHITECT] = 0.00 + 1.04 [TDx] for samples within the range of 0.040 to 1624.760 µmol/L MTX , n = 142). Specimen storage study denoted that specimens could be stored at room temperature for 24 hours or at 2-8oC for 48 hours since the MTX values of the stored specimens described above were within 10% deviation from that of the baseline control specimens. Specimen Tube type study demonstrated that specimens collected in K2-EDTA, sodium heparin, and lithium heparin tubes was within ± 10% deviation from that collected in serum tubes across the range of 0.040 to 10.00 μmol/L MTX. Reagent on-board stability showed that the ARCHITECT Methotrexate reagents could remain on the analyzer for a minimum of 30 days with no more than 10% shift from baseline. CONCLUSION: The ARCHITECT Methotrexate under development was demonstrated to be an accurate, precise, sensitive and robust assay for the measurement of Methotrexate in human serum and plasma. Citation Format: Robert J. Smalley, Raymond E. Picard, Beth A. Burkhart, Robert L. Frescatore, Curtis L. Glover, Lisa C. Zhu, Elizabeth A. Roessner, Karin MajnesjÖ, Anders Öhrvik, Kuanglin He, Zhong Qian Li, Timothy R. Kettlety. An immunoassay for measurement of methotrexate on ARCHITECT i system. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3678. doi:10.1158/1538-7445.AM2014-3678