The rockefeller university

Psoriasis is an autoimmune disease that affects approximately 100 million people worldwide, and is a disease that can be ameliorated by anti-cytokine treatment. We aimed to compare the efficacy and safety of risankizumab with adalimumab in patients with moderate-to-severe plaque psoriasis. IMMvent was a phase 3, randomised, double-blind, active-comparator-controlled trial completed at 66 clinics in 11 countries. Eligible patients were aged 18 years or older with moderate-to-severe chronic plaque psoriasis. Patients were randomly assigned 1:1 using interactive response technology to receive 150 mg risankizumab subcutaneously at weeks 0 and 4 or 80 mg adalimumab subcutaneously at randomisation, then 40 mg at weeks 1, 3, 5, and every other week thereafter during a 16-week double-blind treatment period (part A). For weeks 16-44 (part B), adalimumab intermediate responders were re-randomised 1:1 to continue 40 mg adalimumab or switch to 150 mg risankizumab. In part A, participants and investigators were masked to study treatment. Randomisation was stratified by weight and previous tumour necrosis factor inhibitor exposure. Co-primary endpoints in part A were a 90% improvement from baseline (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16, and for part B was PASI 90 at week 44 (non-responder imputation). Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the safety population (all patients who received at least one dose of study drug or placebo). This study is registered with ClinicalTrials.gov, number NCT02694523. Between March 31, 2016, and Aug 24, 2017, 605 patients were randomly assigned to receive either risankizumab (n=301, 50%) or adalimumab (n=304, 50%). 294 (98%) of patients in the risankizumab group and 291 (96%) in the adalimumab group completed part A, and 51 (96%) of 53 patients re-randomised to risankizumab and 51 (91%) of 56 patients re-randomised to continue adalimumab completed part B. At week 16, PASI 90 was achieved in 218 (72%) of 301 patients given risankizumab and 144 (47%) of 304 patients given adalimumab (adjusted absolute difference 24·9% [95% CI 17·5-32·4]; p<0·0001), and sPGA scores of 0 or 1 were achieved in 252 (84%) patients given risankizumab and 252 (60%) patients given adalimumab (adjusted absolute difference 23·3% [16·6-30·1]; p<0·0001). In part B, among adalimumab intermediate responders, PASI 90 was achieved by 35 (66%) of 53 patients switched to risankizumab and 12 (21%) of 56 patients continuing adalimumab (adjusted absolute difference 45·0% [28·9-61·1]; p<0·0001) at week 44. Adverse events were reported in 168 (56%) of 301 patients given risankizumab and 179 (57%) of 304 patients given adalimumab in part A, and among adalimumab intermediate responders, adverse events were reported in 40 (75%) of 53 patients who switched to risankizumab and 37 (66%) of 56 patients who continued adalimumab in part B. Risankizumab showed significantly greater efficacy than adalimumab in providing skin clearance in patients with moderate-to-severe plaque psoriasis. No additional safety concerns were identified for patients who switched from adalimumab to risankizumab. Treatment with risankizumab provides flexibility in the long-term treatment of psoriasis.

BACKGROUND & AIMS: Barrett's esophagus (BE) is a precursor to esophageal

Protein degradation by the ubiquitin-proteasome system is critical for

Typical avian eyes are phenotypically engineered for photopic vision

Background

Studies of vertebrate immunity have traditionally focused on professional cells, including circulating and tissue-resident leukocytes. Evidence that non-professional cells are also intrinsically essential (i.e. not via their effect on leukocytes) for protective immunity in natural conditions of infection has emerged from three lines of research in human genetics. First, studies of Mendelian resistance to infection have revealed an essential role of DARC-expressing erythrocytes in protection against Plasmodium vivax infection, and an essential role of FUT2-expressing intestinal epithelial cells for protection against norovirus and rotavirus infections. Second, studies of inborn errors of non-hematopoietic cell-extrinsic immunity have shown that APOL1 and complement cascade components secreted by hepatocytes are essential for protective immunity to trypanosome and pyogenic bacteria, respectively. Third, studies of inborn errors of non-hematopoietic cell-intrinsic immunity have suggested that keratinocytes, pulmonary epithelial cells, and cortical neurons are essential for tissue-specific protective immunity to human papillomaviruses, influenza virus, and herpes simplex virus, respectively. Various other types of genetic resistance or predisposition to infection in human populations are not readily explained by inborn variants of genes operating in leukocytes and may, therefore, involve defects in other cells. The probing of this unchartered territory by human genetics is reshaping immunology, by scaling immunity to infection up from the immune system to the whole organism.

Despite evidence linking the human microbiome to health and disease, how

The vertebrate toll-like receptor (TLRs) supergene family is a

IntroductionPharmaceutical firms have begun offering online prescription

Aim To assess progressive learning of root canal shaping in order to