IL ‐17 Inhibition in Spondyloarthritis Associates with Subclinical Gut Microbiome Perturbations and a Distinctive IL‐25‐Driven Intestinal Inflammation

AbstractObjectiveTo characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome of psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients.MethodsFecal samples from PsA/SpA patients pre ‐ and post‐treatment with tumor necrosis factor inhibitors (TNFi; n=15) or an anti‐interleukin (IL)‐17A monoclonal antibody inhibitor (IL‐17i; n=14) underwent sequencing (16S, ITS and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cy tokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL‐17i (n=5) were analyzed for expression of IL‐23/T h‐17 related cytokines, IL‐25/IL‐17E‐producing cells and type‐2 innate lymphoid cells (ILC2s).ResultsThere were significant shifts in abundance of specific taxa after treatment with IL ‐17i compared to TNFi, particularly Clostridiales (p=0.016) andCandida albicans (p=0.041). These subclinical alterations correlated with changes in bacterial community co ‐occurrence, metabolic pathways, IL‐23/Th17‐related cytokines and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL‐25/IL‐17E‐producing tuft cells and ILC2s (p
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Full Length Source Type: research

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Pfizer Inc. (NYSE: PFE) announced the United States (U.S.) Food and Drug Administration (FDA) has approved ABRILADA™ (adalimumab-afzb), as a biosimilar to Humira® (adalimumab),(1) for the treatment of certain patients with rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn's disease, ulcerative colitis and plaque psoriasis.(2)
Source: World Pharma News - Category: Pharmaceuticals Tags: Featured Pfizer Business and Industry Source Type: news
ConclusionThe safety profile of adalimumab was consistent with previous findings and no new safety signals were observed.
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research
Ustekinumab, a monoclonal antibody that targets interleukin (IL)-12/23, is used to treat psoriasis, psoriatic arthritis and Crohn disease. In 2011, a meta-analysis of randomized trials alerted on a potential risk of major adverse cardiovascular events (MACE) within the first months after the initiation of anti-IL-12/23 antibodies. Our objective was to assess if ustekinumab initiation may trigger MACE. Using the French National Health Insurance database, covering 66 million subjects, we included all patients exposed to ustekinumab between 2010 and 2016, classified according to their cardiovascular risk level (high vs.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Clinical Research and Epidemiology Source Type: research
CONCLUSION: Based on our systematic review, the epidemiology of IMIDs among immigrants varies according to native and host countries, immigrant generation, and IMID type. The rapid evolution suggests a role for non-genetic factors and gene-environment interactions. Future studies should focus on these pattern shifts, given implications of rising global burden of IMIDs and immigration. PMID: 31351784 [PubMed - as supplied by publisher]
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research
This study evaluated the impact of the HUMIRA Complete Pro (HCPro) online prescription management system on the rate of abandonment and the time to first fill for patients prescribed adalimumab (ADA). A retrospective cohort analysis of patients initiating ADA treatment with or without use of the HCPro online prescription processing system was used to evaluate the impact of HCPro on treatment initiation outcomes.MethodsPatient-level data for patients with an ADA prescription processed through HCPro were mapped to Symphony Health claims for patients initiating ADA between January 2012 and January 2015. The sample included pa...
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research
This article summarizes the milestones in the development of risankizumab leading to this first approval for psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis and erythrodermic psoriasis.
Source: Drugs - Category: Drugs & Pharmacology Source Type: research
We presented a new statistic T to use large public database as reference to reduce concern of potential population stratification. And the new statistic proposed here is effective to discover novel genome-wide significant loci with both small and large sample sizes. Author Contributions YW conceived the idea and developed the software. YL, MH, and XL contributed data analysis, generating tables and figures, and manuscript writing. YW, YL, MH, XL, YS, and LJ contributed the theoretical analysis and manuscript revision. MX helped support the GWAS datasets. YW, YL, MH, XL, MZ, JW, and MX contributed to scientific discussion...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Authors: Puig L Abstract INTRODUCTION: IL-23 is the key regulatory cytokine of T17-mediated inflammation in psoriasis. Guselkumab is a subcutaneously administered monoclonal antibody that targets the p19 cytokine subunit in IL-23 and has been approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of moderate-to-severe psoriasis in adult patients. Areas covered: This review outlines the pharmacologic properties, efficacy and safety of guselkumab for the treatment of moderate-to-severe plaque psoriasis in adults. A literature review was performed by searching PubMed. Exper...
Source: Expert Review of Clinical Immunology - Category: Allergy & Immunology Tags: Expert Rev Clin Immunol Source Type: research
Conclusions: The primary goal of pharmacodynamic monitoring is to optimize the response, but it can also have an impact on safety, costs, patient adherence, etc. Ideally, the constant remote monitoring of patient-reported disease activity is expected to become the standard, facilitated by mHealth technologies.
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research
Introduction: There is a need for effective and safe treatment during pregnancy in women with chronic inflammatory diseases (rheumatoid arthritis/axial spondyloarthritis/psoriatic arthritis/Crohn's disease). Adequate disease control is crucial to reduce the risk of adverse pregnancy outcomes. Anti-TNFs are effective therapies, but because most cross the placenta they are often stopped during pregnancy. Certolizumab pegol (CZP), due to its Fc-free molecular structure, is not expected to undergo placental transfer compared to other anti-TNFs.
Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology - Category: OBGYN Authors: Tags: Basic Science 6 – Teratology genetics and outcomes Source Type: research
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