Abstract
Interleukin-1 inhibitors were tested in large arthritis trials with less than impressive results, despite having convincing disease expression data and pre-clinical animal model supporting the potential pathogenic role of this cytokine in these settings. Despite disappointing beginnings, some IL-1 pathway blocking drugs are now beginning to find a place in the pharmacopoeia of rheumatologists. Drug developers utilised rapidly growing understanding of the molecular pathway and the genetic basis of key diseases to seek out conditions in which IL-1 pathway activation was much more likely to have a pivotal role in disease pathogenesis compared to the major arthritides. This review details the crucial advances in understanding of the IL-1 pathway activation which enabled this progress, particularly the advent of inflammasome biology. The drug development of IL-1 biologics in rheumatological diseases makes a fascinating case study illustrating major changes in drug development strategy encompassing closer synergies between translational biology, underlying molecular pathophysiology of disease, and novel clinical development pathways of biologic therapeutics.
Keywords: Interleukin, interleukin-1, inflammasome, rheumatology, cryopyrin, gout, arthritis, CAPS.
Current Pharmaceutical Design
Title:Finding a Place for Interleukin-1 Inhibitors in the Treatment of Rheumatologic Diseases
Volume: 21 Issue: 17
Author(s): Donna Finch and Matthew Sleeman
Affiliation:
Keywords: Interleukin, interleukin-1, inflammasome, rheumatology, cryopyrin, gout, arthritis, CAPS.
Abstract: Interleukin-1 inhibitors were tested in large arthritis trials with less than impressive results, despite having convincing disease expression data and pre-clinical animal model supporting the potential pathogenic role of this cytokine in these settings. Despite disappointing beginnings, some IL-1 pathway blocking drugs are now beginning to find a place in the pharmacopoeia of rheumatologists. Drug developers utilised rapidly growing understanding of the molecular pathway and the genetic basis of key diseases to seek out conditions in which IL-1 pathway activation was much more likely to have a pivotal role in disease pathogenesis compared to the major arthritides. This review details the crucial advances in understanding of the IL-1 pathway activation which enabled this progress, particularly the advent of inflammasome biology. The drug development of IL-1 biologics in rheumatological diseases makes a fascinating case study illustrating major changes in drug development strategy encompassing closer synergies between translational biology, underlying molecular pathophysiology of disease, and novel clinical development pathways of biologic therapeutics.
Export Options
About this article
Cite this article as:
Finch Donna and Sleeman Matthew, Finding a Place for Interleukin-1 Inhibitors in the Treatment of Rheumatologic Diseases, Current Pharmaceutical Design 2015; 21 (17) . https://dx.doi.org/10.2174/1381612821666150310144603
DOI https://dx.doi.org/10.2174/1381612821666150310144603 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Advances and Implications in Nanotechnology for Lung Cancer Management
Current Drug Metabolism The Epidemiology and Health Effects of Tobacco Use
Current Pediatric Reviews Editorial (Thematic Issue: Clinical Advances in Immuno-oncology – Progress Towards Selective Cure)
Current Molecular Pharmacology A New Application Route of Nitrofurantoin: Preparation and Characterization of Novel Transdermal Formulations
Current Drug Delivery Biochemical, Biomedical and Metabolic Aspects of Imidazole-Containing Dipeptides with the Inherent Complexity to Neurodegenerative Diseases and Various States of Mental Well-Being: A Challenging Correction and Neurotherapeutic Pharmaceutical Biotechnology for Treating Cognitive Deficits, Depression and Intellectual Disabilities
Current Pharmaceutical Biotechnology Emerging Technologies in Biocompatible Surface Modifying Additives: Quest for Physiologic Cardiopulmonary Bypass
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Nitric Oxide and Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Catestatin: A Master Regulator of Cardiovascular Functions
Current Medicinal Chemistry Modified cAMP Derivatives: Powerful Tools in Heart Research
Current Medicinal Chemistry Vasomotor Effects of Iodinated Contrast Media: Just Side Effects?
Current Vascular Pharmacology rDNA Mediated Bioconjugates: Fusion Proteins and their Intended Use in Medicine
Current Topics in Medicinal Chemistry Leptin, Immune Responses and Autoimmune Disease. Perspectives on the Use of Leptin Antagonists
Current Pharmaceutical Design Vitamin A, D & Zinc Serum Levels in Children with Acute Gastroentritis: A Case Control Study: Tehran, Iran
Current Nutrition & Food Science Relevance of Aβ 1-42 Intrahippocampal Injection as An Animal Model of Inflamed Alzheimers Disease Brain
Current Alzheimer Research New Perspectives on the Structure and Function of the Na+ Channel Multigene Family
Current Medicinal Chemistry - Central Nervous System Agents Cyclooxygenase-2: Potential Role in Regulation of Drug Efflux and Multidrug Resistance Phenotype
Current Pharmaceutical Design γ-Secretase as a Target for Alzheimers Disease
Current Topics in Medicinal Chemistry Heart Transplantation for Congenital Heart Disease in the First Year of Life
Current Cardiology Reviews Perioperative Management of Intracranial Aneurysm and Subarachnoid Hemorrhage
Current Pharmaceutical Design Regulation of Innate and Adaptive Immune Responses by a Novel Pattern Recognition Molecule Mindin
Current Immunology Reviews (Discontinued)