The 2021 EULAR/American College of Rheumatology points to consider for diagnosis, management and monitoring of the interleukin-1 mediated autoinflammatory diseases: cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic syndrome, mevalonate kinase deficiency, and deficiency of the interleukin-1 receptor antagonist

Micol Romano^#¹, Z Serap Arici^#², David Piskin^#³, Sara Alehashemi⁴, Daniel Aletaha⁵, Karyl S Barron⁶, Susanne Benseler⁷, Roberta Berard⁸, Lori Broderick⁹, Fatma Dedeoglu¹⁰, Michelle Diebold¹¹, Karen L Durrant¹², Polly Ferguson¹³, Dirk Foell¹⁴, Jonathan Hausmann¹⁵, Olcay Y Jones¹⁶, Daniel L Kastner⁶, Helen J Lachmann¹⁷, Ronald M Laxer¹⁸, Dorelia Rivera¹², Nicolino Ruperto¹⁹, Anna Simon²⁰, Marinka Twilt⁷, Joost Frenkel²¹, Hal Hoffman²², Adriana A de Jesus²³, Jasmin Beate Kuemmerle-Deschner²⁴, Seza Ozen²⁵, Marco Gattorno^{26

27}, Raphaela Goldbach-Mansky²⁸, Erkan Demirkaya²⁹

Affiliations

¹ Department of Pediatrics, Division of Pediatric Rheumatology, Behcet and Autoinflammatory Disease Center, Western University, London, Ontario, Canada.
² Department of Pediatric Rheumatology, Sanliurfa Mehmet Akif Inan Training and Research Hospital, Sanliurfa, Sanliurfa, Turkey.
³ Lawson Health Research Institute and Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
⁴ Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology (LCIM), NIAID, NIH, Bethesda, Maryland, USA.
⁵ Division of Rheumatology, Medical University of Vienna, Wien, Austria.
⁶ Division of Intramural Research, National Institute of Allergy and Immunology, NIH, Bethesda, Maryland, USA.
⁷ Division of Rheumatology, Department of Pediatrics, Alberta Children's Hospital, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
⁸ Division of Pediatric Rheumatology, Department of Paediatrics, Schulich School of Medicine&Dentistry, Western University, London, Ontario, Canada.
⁹ Division of Pediatric Allergy, Immunology, and Rheumatology, University of California and Rady Children's Hospital, San Diego, California, USA.
¹⁰ Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Division of Pediatric Rheumatology, Department of Paediatrics, LHSC Children's Hospital, London, Ontario, Canada.
¹² Autoinflammatory Alliance, San Francisco, California, USA.
¹³ Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
¹⁴ Department of Pediatric Rheumatology and Immunology, University of Muenster, Muenster, Germany.
¹⁵ Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
¹⁶ Department of Pediatrics, Walter Reed National Military Medical Center (WRNMMC), Bethesda, Maryland, USA.
¹⁷ Department of Medicine, University College London, London, UK.
¹⁸ Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada.
¹⁹ IRCCS Istituto Giannina Gaslini, UOSID Centro Trial, Genova, Italy.
²⁰ Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
²¹ Department of Pediatrics, Wilhelmina Kinderziekenhuis Polikliniek Algemene Kindergeneeskunde, Utrecht, Utrecht, The Netherlands.
²² Division of Pediatric Allergy, Immunology, and Rheumatology, University of California at San Diego, San Diego, California, USA.
²³ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
²⁴ Division of Pediatric Rheumatology, Department of Pediatrics, University Hospital Tuebingen, Tübingen, Germany.
²⁵ Department of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.
²⁶ UOSD Centro Malattie Autoinfiammatorie e Immunodeficienze, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
²⁷ Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini.
²⁸ Translational Autoinflammatory Diseases Section (TADS), National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
²⁹ Division of Paediatric Rheumatology, Department of Paediatrics, Behcet and Autoinflammatory Disease Center and Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada Erkan.Demirkaya@lhsc.on.ca.

^# Contributed equally.

PMID: 35623638
DOI: 10.1136/annrheumdis-2021-221801

Free article

Practice Guideline

The 2021 EULAR/American College of Rheumatology points to consider for diagnosis, management and monitoring of the interleukin-1 mediated autoinflammatory diseases: cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic syndrome, mevalonate kinase deficiency, and deficiency of the interleukin-1 receptor antagonist

Micol Romano et al. Ann Rheum Dis. 2022 Jul.

Free article

. 2022 Jul;81(7):907-921.

doi: 10.1136/annrheumdis-2021-221801. Epub 2022 May 27.

Authors

Affiliations

¹ Department of Pediatrics, Division of Pediatric Rheumatology, Behcet and Autoinflammatory Disease Center, Western University, London, Ontario, Canada.
² Department of Pediatric Rheumatology, Sanliurfa Mehmet Akif Inan Training and Research Hospital, Sanliurfa, Sanliurfa, Turkey.
³ Lawson Health Research Institute and Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
⁴ Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology (LCIM), NIAID, NIH, Bethesda, Maryland, USA.
⁵ Division of Rheumatology, Medical University of Vienna, Wien, Austria.
⁶ Division of Intramural Research, National Institute of Allergy and Immunology, NIH, Bethesda, Maryland, USA.
⁷ Division of Rheumatology, Department of Pediatrics, Alberta Children's Hospital, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
⁸ Division of Pediatric Rheumatology, Department of Paediatrics, Schulich School of Medicine&Dentistry, Western University, London, Ontario, Canada.
⁹ Division of Pediatric Allergy, Immunology, and Rheumatology, University of California and Rady Children's Hospital, San Diego, California, USA.
¹⁰ Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Division of Pediatric Rheumatology, Department of Paediatrics, LHSC Children's Hospital, London, Ontario, Canada.
¹² Autoinflammatory Alliance, San Francisco, California, USA.
¹³ Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
¹⁴ Department of Pediatric Rheumatology and Immunology, University of Muenster, Muenster, Germany.
¹⁵ Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.
¹⁶ Department of Pediatrics, Walter Reed National Military Medical Center (WRNMMC), Bethesda, Maryland, USA.
¹⁷ Department of Medicine, University College London, London, UK.
¹⁸ Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada.
¹⁹ IRCCS Istituto Giannina Gaslini, UOSID Centro Trial, Genova, Italy.
²⁰ Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
²¹ Department of Pediatrics, Wilhelmina Kinderziekenhuis Polikliniek Algemene Kindergeneeskunde, Utrecht, Utrecht, The Netherlands.
²² Division of Pediatric Allergy, Immunology, and Rheumatology, University of California at San Diego, San Diego, California, USA.
²³ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
²⁴ Division of Pediatric Rheumatology, Department of Pediatrics, University Hospital Tuebingen, Tübingen, Germany.
²⁵ Department of Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.
²⁶ UOSD Centro Malattie Autoinfiammatorie e Immunodeficienze, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
²⁷ Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini.
²⁸ Translational Autoinflammatory Diseases Section (TADS), National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
²⁹ Division of Paediatric Rheumatology, Department of Paediatrics, Behcet and Autoinflammatory Disease Center and Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada Erkan.Demirkaya@lhsc.on.ca.

^# Contributed equally.

PMID: 35623638
DOI: 10.1136/annrheumdis-2021-221801

Abstract

Background: The interleukin-1 (IL-1) mediated systemic autoinflammatory diseases, including the cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD) and deficiency of the IL-1 receptor antagonist (DIRA), belong to a group of rare immunodysregulatory diseases that primarily present in early childhood with variable multiorgan involvement. When untreated, patients with severe clinical phenotypes have a poor prognosis, and diagnosis and management of these patients can be challenging. However, approved treatments targeting the proinflammatory cytokine IL-1 have been life changing and have significantly improved patient outcomes.

Objective: To establish evidence-based recommendations for diagnosis, treatment and monitoring of patients with IL-1 mediated autoinflammatory diseases to standardise their management.

Methods: A multinational, multidisciplinary task force consisting of physician experts, including rheumatologists, patients or caregivers and allied healthcare professionals, was established. Evidence synthesis, including systematic literature review and expert consensus (Delphi) via surveys, was conducted. Consensus methodology was used to formulate and vote on statements to guide optimal patient care.

Results: The task force devised five overarching principles, 14 statements related to diagnosis, 10 on therapy, and nine focused on long-term monitoring that were evidence and/or consensus-based for patients with IL-1 mediated diseases. An outline was developed for disease-specific monitoring of inflammation-induced organ damage progression and reported treatments of CAPS, TRAPS, MKD and DIRA.

Conclusion: The 2021 EULAR/American College of Rheumatology points to consider represent state-of-the-art knowledge based on published data and expert opinion to guide diagnostic evaluation, treatment and monitoring of patients with CAPS, TRAPS, MKD and DIRA, and to standardise and improve care, quality of life and disease outcomes.

Keywords: Cryopyrin-Associated Periodic Syndromes; Cytokines; Inflammation; Interleukin 1 Receptor Antagonist Protein.

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Conflict of interest statement

Competing interests: DA: received grants from AbbVie, Amgen, Lilly, Novartis, Roche, Sooi and Sanofi; received consulting fees from Abbvie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz; received lecture fees from Lilly, Merck, Pfizer, Roche and Sandoz. RB: received consultation fees from Sandoz and Roche. LB: received grants from Novartis and Regeneron FD: received consulting fees from Novartis. KLD: is the president of the Autoinflammatory Alliance. PF: received grants from NIH, CARRA, Inc; consulting fees from Novartis. DF: received grants from Novartis and Sobi; received consultation fees from Boehringer Ingelheim, Chugai-Roche, Merck, Novartis and Sobi; received lecture fees from Novartis, Peer Voice and Sobi. JH: received grants from CARRA and Sobi; consultation fees from Novartis, Biogen and Pfizer. RML: received consultation fees from Novartis and he is participating on a Data Safety Monitoring/advisory Board of Sobi, Novartis, Sanofi. NR: received consulting fees from Ablynx, Amgen, AstraZeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squib, Cambridge Healthcare Research, Celgene, Domain Therapeutic, Eli Lilly, EMD Serono, GSK, Idorsia, Janssen, Novartis, Sobi, Pfizer and UCB; received lecture fees from Eli Lilly, GSK, Pfizer, Sobi and UCB; he is member of advisory boards of Pfizer and Eli Lilly. HH: received grants from Bristol Meyer Squib, Jecure, Takeda and Zomagen; received consulting fees from Novartis, Regeneron, Sobi and Aclaris, received advisory board fees from Novartis and IFM. JBK-D: received grants from Novartis and Sobi; received consulting fees from Novartis; received payment for lectures from Novartis and Sobi; received advisory board fees from Novartis. SO: lectures fees from Novartis and Sobi; meeting support from Sobi, AbbVie and Pfizer; advisory board payment from Novartis. MG: received grants from Novartis; received consultation and lecture fees from Novartis and Sobi. RG-M: received study support under government CRADAs from Eli Lilly, IFM and Sobi. ED: received grants from Sobi.

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