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A blood test identifying patients at increased risk of pulmonary hypertension (PH) could streamline the investigative pathway. The prospective, multicenter CIPHER study aimed to develop a microRNA‐based signature for detecting PH in breathless patients and enrolled adults with a high suspicion of PH who had undergone right heart catheterization (RHC). The CIPHER‐MRI study was added to assess the performance of this CIPHER signature in a population with low probability of having PH who underwent cardiac magnetic resonance imaging (cMRI) instead of RHC. The microRNA signature was developed using a penalized linear regression (LASSO) model. Data were modeled both with and without N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). Signature performance was assessed against predefined thresholds (lower 98.7% CI bound of ≥0.73 for sensitivity and ≥0.53 for specificity, based on a meta‐analysis of echocardiographic data), using RHC as the true diagnosis. Overall, 926 CIPHER participants were screened and 888 were included in the analysis. Of 688 RHC‐confirmed PH cases, approximately 40% were already receiving PH treatment. Fifty microRNA (from 311 investigated) were algorithmically selected to be included in the signature. Sensitivity [97.5% CI] of the signature was 0.85 [0.80–0.89] for microRNA‐alone and 0.90 [0.86–0.93] for microRNA+NT‐proBNP, and the corresponding specificities were 0.33 [0.24–0.44] and 0.28 [0.20–0.39]. Of 80 CIPHER‐MRI participants with evaluable data, 7 were considered PH‐positive by cMRI whereas 52 were considered PH‐positive by the microRNA signature. Due to low specificity, the CIPHER miRNA‐based signature for PH (either with or without NT‐proBNP in model) did not meet the prespecified diagnostic threshold for the primary analysis. [ABSTRACT FROM AUTHOR]

A placebo-controlled randomized study is conducted to examine the effectiveness of the human anti-interleukin-1beta monoclonal antibody canakinumab in the treatment of the cryopyrin-associated periodic syndrome (CAPS), an inflammatory disease associated with excess production of interleukin-1. Results suggest that canakinumab is rapidly and significantly effective over a long period in treating patients with CAPS.

Abstract Background Canakinumab is a fully human anti-interleukin IL-1beta monoclonal antibody, being investigated for the treatment of rheumatoid arthritis (RA). This multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study investigated the efficacy and safety of canakinumab in patients with active RA despite ongoing therapy at stable doses of methotrexate. Methods Patients were randomized to receive one of four regimens, in addition to methotrexate, for 12 weeks: canakinumab 150 mg subcutaneously (SC) every 4 weeks (q4wk), canakinumab 300 mg SC (2 injections of 150 mg SC) every 2 weeks, a 600 mg intravenous loading dose of canakinumab followed by 300 mg SC every 2 weeks', or placebo SC every 2 weeks. Results Among 274 patients with evaluable efficacy data, the percentage of responders according to American College of Rheumatology 50 criteria (the primary endpoint, based on a 28-joint count) was significantly higher with canakinumab 150 mg SC q4wk than with placebo (26.5% vs. 11.4%, respectively; p = 0.028). Compared to placebo, this dosage of canakinumab was also associated with significantly more favorable responses at week 12 with respect to secondary endpoints including the Disease Activity Score 28, scores on the Health Assessment Questionnaire and Functional Assessment of Chronic Illness Therapy-Fatigue, swollen 28-joint count, and patient's and physician's global assessments of disease activity. No safety concerns were raised with canakinumab therapy, particularly with regard to infections. Few injection-site reactions occurred. Conclusion The addition of canakinumab 150 mg SC q4wk improves therapeutic responses among patients who have active RA despite stable treatment with methotrexate. Trial Registration (ClinicalTrials.gov identifier: NCT00784628)