28043 Roflumilast cream significantly improves chronic plaque psoriasis in patients with steroid-sensitive area involvement

Roflumilast cream is a nonsteroidal, selective phosphodiesterase-4 inhibitor in development for plaque psoriasis (PsO). A double-blind, phase 2b trial randomized adults with PsO to once daily roflumilast 0.3%, 0.15%, or vehicle for 12 weeks (NCT03638258).(1) Efficacy was assessed using Investigator Global Assessment (IGA), Worst Itch Numeric Rating Scale (WI–NRS), and Psoriasis Symptom Diary (PSD). This posthoc analysis reports efficacy and safety in patients with steroid-sensitive area involvement (plaques on the face, neck, or in intertriginous areas). Of 331 patients, 160 had steroid-sensitive area involvement. The primary endpoint in the study, IGA status clear/almost clear at Week 6 was met by 27.2% patients with steroid sensitive areas (P =.007 vs vehicle), 22.3% (P =.026), and 6.3% on roflumilast 0.3%, roflumilast 0.15%, and vehicle, respectively; relative to 30.1% (P =.026), 24.1% (P =.098), and 12.0% patients without steroid-sensitive areas. Among patients with baseline WI–NRS score ≥4, 73.5%, 55.6%, and 32.6% of those with steroid-sensitive areas and 45.9%, 72.7%, and 23.7% of those without steroid-sensitive areas achieved a 4-point reduction with roflumilast 0.3%, 0.15%, or vehicle at Week 12. PSD improvement from baseline at Week 12 for patients with steroid-sensitive areas was -48.3 (P ˂.001), -43.1 (P =.012), and -24.9, and for patients without steroid-sensitive areas -35.7 (P =.003), -44.6 (P ˂.001), and -17.1. Most treatment emergent adverse events were mild to moderate and there was no evidence of local irritation. Once-daily roflumilast cream was well tolerated with significant improvements in investigator and patient assessed PsO outcomes in patients with steroid-sensitive area involvement on the face, neck, or intertriginous areas

27874 Correlation of itch response to roflumilast cream with disease severity and patient-reported outcomes in patients with chronic plaque psoriasis

Roflumilast cream is a nonsteroidal, selective phosphodiesterase-4 inhibitor in development for plaque psoriasis (PsO). A Phase 2b, double-blinded trial randomized adults with PsO (2-20% body surface area) to once daily roflumilast 0.3%, roflumilast 0.15%, or vehicle for 12 weeks (NCT03638258). Throughout the trial, itch and its impact were evaluated via patient reported outcomes (PROs): Worst Itch Numeric Rating Scale (WI–NRS), Itch related Sleep Loss (IRSL), and Dermatology Life Quality Index (DLQI). This posthoc analysis reports correlation of WI–NRS with other PROs and with disease severity. Overall, 331 patients were randomized (109 to roflumilast 0.3%, 113 to 0.15%, and 109 to vehicle). At baseline, the mean WI–NRS score was 5.87. Throughout the trial, both roflumilast doses showed similar improvements in WI–NRS starting at Week 2 and were significantly superior to vehicle (P ≤.002). At baseline, Pearson correlation coefficients (PCCs) for WI–NRS and Psoriasis Area and Severity Index (PASI) were 0.189, 0.282, 0.205 for roflumilast 0.3%, roflumilast 0.15%, and vehicle, respectively (P ≤.033 for all correlations); for WI–NRS and IRSL: 0.548, 0.646, 0.652 (P ˂.001); for WI–NRS and DLQI: 0.445, 0.617, 0.422 (P ˂.001). At Week 8, PCCs for WI–NRS and PASI were 0.420, 0.409, 0.365 (P ˂.001); for WI–NRS and IRSL: 0.673, 0.725, 0.696 (P ˂.001); for WI–NRS and DLQI: 0.607, 0.823, 0.529. Treatment with roflumilast resulted in rapid and robust improvement in the severity of itch associated with PsO. Itch response to roflumilast was independent of disease severity and positively correlated with patient-reported sleep loss and quality of life improvement

Trends in Hospitalizations for Peptic Ulcer Disease, United States, 1998–20051

TOC summary: Decreased hospitalization rates suggest decline in complications from Helicobacter pylori infection

The dominant ethnic moment: towards the abolition of 'whiteness'?

International audienc

Antigen-specific immunotherapy with thyrotropin receptor peptides in Grave's Hyperthyroidism: a Phase I study

Graves' disease is one of the most common autoimmune conditions, but treatment remains imperfect. This study explores the first-in-human use of antigen-specific immunotherapy with a combination of two thyrotropin receptor (TSHR) peptides (termed ATX-GD-59) in Graves' hyperthyroidism.This article is freely available via Open Access. Click on the Publisher's URL to access the full-text via the publisher's site.Publishe

Age of the Association between Helicobacter pylori and Man

When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts. But how long were humans infected by H. pylori prior to the out-of-Africa event? Did this co-evolution predate the emergence of modern humans, spanning the species divide? To answer these questions, we investigated the diversity of H. pylori in Africa, where both humans and H. pylori originated. Three distinct H. pylori populations are native to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a sustained co-evolution over millions of years, we find that the coalescent for all H. pylori plus its closest relative H. acinonychis dates to 88–116 kya. At that time the phylogeny split into two primary super-lineages, one of which is associated with the former hunter-gatherers in southern Africa known as the San. H. acinonychis, which infects large felines, resulted from a later host jump from the San, 43–56 kya. These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities show that H. pylori is approximately as old as are anatomically modern humans. They also suggest that H. pylori may have been acquired via a single host jump from an unknown, non-human host. We also find evidence for a second Out of Africa migration in the last 52,000 years, because hpEurope is a hybrid population between hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa 36–52 kya, after the Out of Africa migrations around 60 kya

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk