Predictors of British Isles Lupus Assessment Group-based outcomes in patients with systemic lupus erythematosus: Analysis from the Systemic Lupus International Collaborating Clinics Inception Cohort.

BACKGROUND: We aimed to identify factors associated with a significant reduction in SLE disease activity over 12 months assessed by the BILAG Index. METHODS: In an international SLE cohort, we studied patients from their 'inception enrolment' visit. We also defined an 'active disease' cohort of patients who had active disease similar to that needed for enrolment into clinical trials. Outcomes at 12 months were; Major Clinical Response (MCR: reduction to classic BILAG C in all domains, steroid dose of ≤7.5 mg and SLEDAI ≤ 4) and 'Improvement' (reduction to ≤1B score in previously active organs; no new BILAG A/B; stable or reduced steroid dose; no increase in SLEDAI). Univariate and multivariate logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) and cross-validation in randomly split samples were used to build prediction models. RESULTS: 'Inception enrolment' (n = 1492) and 'active disease' (n = 924) patients were studied. Models for MCR performed well (ROC AUC = .777 and .732 in the inception enrolment and active disease cohorts, respectively). Models for Improvement performed poorly (ROC AUC = .574 in the active disease cohort). MCR in both cohorts was associated with anti-malarial use and inversely associated with active disease at baseline (BILAG or SLEDAI) scores, BILAG haematological A/B scores, higher steroid dose and immunosuppressive use. CONCLUSION: Baseline predictors of response in SLE can help identify patients in clinic who are less likely to respond to standard therapy. They are also important as stratification factors when designing clinical trials in order to better standardize overall usual care response rates.

Novel oral iron therapy for iron deficiency anaemia: How to value safety in a new drug?

AIMS: Novel oral iron supplements may be associated with a reduced incidence of adverse drug reactions compared to standard treatments of iron deficiency anaemia. The aim was to establish their value-based price under conditions of uncertainty surrounding their tolerability. METHODS: A discrete-time Markov model was developed to assess the value-based price of oral iron preparations based on their incremental cost per quality-adjusted life year (QALY) gained from the perspective of the NHS in the UK. Primary and secondary care resource use and health state occupancy probabilities were estimated from routine electronic health records; and unit costs and health state utilities were derived from published sources. Patients were pre-menopausal women with iron deficiency anaemia who were prescribed oral iron supplementation between 2000 and 2014. RESULTS: The model reflecting current use of iron salts yielded a mean total cost to the NHS of £779, and 0.84 QALYs over 12 months. If a new iron preparation were to reduce the risk of adverse drug reactions by 30-40%, then its value-based price, based on a threshold of £20 000 per QALY, would be in the region of £10-£13 per month, or about 7-9 times the average price of basic iron salts. CONCLUSIONS: There are no adequate, direct comparisons of new oral iron supplements to ferrous iron salts, and therefore other approaches are needed to assess their value. Our modelling shows that they are potentially cost-effective at prices that are an order of magnitude higher than existing iron salts.

Role of miRNA-21 in the diagnosis and prediction of treatment efficacy of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) has a poor prognosis and requires early diagnosis and treatment. The aim of the present study was to investigate the difference between microRNA-21 (miRNA-21) expression in the plasma and cerebrospinal fluid (CSF) of patients with PCNSL, and to discuss the importance of miRNA-21 in its diagnostic and therapeutic evaluation. The research subjects were confirmed as patients with PCNSL with histopathological lesions at The First Affiliated Hospital of Harbin Medical University (Harbin, China) between December 2011 and 2017. Comparisons were drawn between the PCNSL, glioblastoma and the healthy control groups. CSF and plasma specimens were obtained from patients with PCNSL prior to chemotherapy, and CSF specimens were also obtained following chemotherapy. Plasma specimens were taken from patients with glioblastoma and the healthy control group. Using reverse transcription-quantitative polymerase chain reaction analysis, it was revealed that plasma miRNA-21 expression level had a notable diagnostic value in distinguishing PCNSL from glioblastoma, another common neurological tumor. Moreover, miRNA-21 expression levels in the plasma correlated positively with those in the CSF. Therefore, miRNA-21 in the plasma may be used as a novel diagnostic biomarker to distinguish patients with PCNSL from those with glioblastoma, whereas miRNA-21 in the CSF may have potential as a predictor of chemotherapeutic effect in PCNSL.