BACKGROUND: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. METHODS: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. RESULTS: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, Castleman's disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. CONCLUSIONS: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.

1st Department of Internal Medicine University of Occupational and Environmental Health Kitakyushu Japan

Center for Immunology of Viral Infections and Auto immune Diseases Université Paris Sud Gif sur Yvette France

Centre for Epidemiology Versus Arthritis The University of Manchester Manchester Academic Health Science Centre Manchester UK

CREATE Centre Section of Rheumatology School of Medicine Division of Infection and Immunity Cardiff University Cardiff UK

Department of Clinical Medicine Copenhagen University Hospital Kobenhavn Denmark

Department of Clinical Medicine University of Copenhagen Kobenhavn Denmark

Department of Clinical Sciences and Community Health ASS G Pini University of Milan Milano Italy

Department of Psychology Health and Technology Enschede Netherlands and Stichting Tools Patient Empowerment University of Twente Enschede The Netherlands

Department of Rheumatology and Clinical Immunology University Medical Center Utrecht Utrecht The Netherlands

Division of Gastroenterology and Hepatology Medical University of Vienna Wien Austria

Division of Rheumatology and Clinical Immunology Internal Medicine 4 Ludwig Maximilians Universitat Munchen Munchen Germany

Division of Rheumatology Department of Internal Medicine Keio University School of Medicine Graduate School of Medicine Shinjuku ku Japan

Division of Rheumatology Geneva University Hospitals Geneve Switzerland

Division of Rheumatology Kantonsspital Sankt Gallen Sankt Gallen Switzerland

Division of Rheumatology Medical University of Vienna Wien Austria

Forschungsbereich Epidemiologie Deutsches Rheuma Forschungszentrum Berlin Berlin Germany

Griffith University School of Medicine Gold Coast Queensland Australia

Immunorhumatologie CHU Lapeyronie Montpellier France

Institute of Cardiovascular and Medical Sciences British Heart Foundation Glasgow Cardiovascular Research Centre Glasgow UK

Institute of Infection Immunity and Inflammation University of Glasgow Glasgow UK

Leeds Teaching Hospitals NHS Trust NIHR Leeds Musculoskeletal Biomedical Research Unit Leeds UK

Mary Kirkland Center for Lupus Research Hospital for Special Surgery New York City New York USA

Medical Humanities Amsterdam University Medical Centres Duivendrecht The Netherlands

Medicine Rheumatology Albany Medical College Albany New York USA

Medicine The University of Texas Southwestern Medical Center Dallas Texas USA

National Institute of Rheumatology and Physiology Semmelweis University Budapest Hungary

Neil Betteridge Associates Limited London UK

Organización Médica de Investigación SA Buenos Aires Argentina

Rheumatology Amsterdam UMC Locatie VUmc Amsterdam The Netherlands

Rheumatology and Clinical Immunology Charite University Hospital Berlin Berlin Germany

Rheumatology Assistance Publique Hôpitaux de Paris Paris France

Rheumatology Brunico Hospital Brunico Italy

Rheumatology Carol Davila University of Medicine and Pharmacy Bucuresti Romania

Rheumatology Department Charles University Praha Czech Republic

Rheumatology Diakonhjemmet Hospital Oslo Norway

Rheumatology Leiden University Medical Center Leiden The Netherlands

Rheumatology Medical University of Graz Graz Austria

Rheumatology Universite Paris Descartes Faculte de Medecine Site Cochin Paris France

Rheumatology University of Pennsylvania Philadelphia Pennsylvania USA

Rheumatology University of Toronto Toronto Ontario Canada

Schools of Medicine and Public Health Division of Infectious Diseases Oregon Health and Science University Portland Oregon USA

Scienze Cliniche e Biologiche Università degli Studi di Torino Torino Italy

Section for Outcomes Research Medical University of Vienna Wien Austria

Translational and Clinical Research Institute Newcastle University Newcastle upon Tyne UK

University of Leeds Leeds Institute of Rheumatic and Musculoskeletal Medicine Leeds UK

UO Pediatria 2 Reumatologia IRCCS Istituto Giannina Gaslini Genova Italy

References provided by Crossref.org

Wound healing: insights into autoimmunity, ageing, and cancer ecosystems through inflammation and IL-6 modulation