The Assessment of SpondyloArthritis International Society (ASAS) Consensus-Based Expert Definition of Difficult-to-Manage, including Treatment-Refractory, Axial Spondyloarthritis

Denis Poddubnyy¹, Victoria Navarro-Compán², Murat Torgutalp³, Suzanne Arends⁴, Sibel Zehra Aydin⁵, Simone Battista⁶, Filip van den Bosch⁷, Christine Bundy⁸, Alberto Cauli⁹, Jo Davies¹⁰, Maxime Dougados¹¹, Tuncay Duruöz¹², Bassel El-Zorkany¹³, Warren Fong¹⁴, Floris van Gaalen¹⁵, Rodrigo Garcia-Salinas¹⁶, Marco Garrido Cumbrera¹⁷, Pál Géher¹⁸, Lianne Gensler¹⁹, Simeon Grazio²⁰, Feng Huang²¹, Mitsumasa Kishimoto²², Robert Landewé²³, Ying Ying Leung²⁴, Pedro M Machado²⁵, Helena Marzo-Ortega²⁶, Bhowmik Meghnathi²⁷, Anna Molto²⁸, Elena Nikiphorou²⁹, Sofia Ramiro¹⁵, Martin Rudwaleit³⁰, Carla G S Saad³¹, Alexandre Sepriano³², James Wei³³, Xenofon Baraliakos³⁴, Désirée van der Heijde³⁵; ASAS

Affiliations

¹ Division of Rheumatology, Department of Medicine, University of Toronto and University Health Network, Toronto, ON, Canada; Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. Electronic address: denis.poddubnyy@uhn.ca.
² Department of Rheumatology, La Paz University Hospital, IdiPaz, Madrid, Spain.
³ Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁴ Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁵ Division of Rheumatology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada; Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁶ Centre for Human Movement and Rehabilitation, School of Health and Society, University of Salford, Salford, Greater Manchester, UK.
⁷ Department of Rheumatology, Ghent University, Ghent University Hospital, Ghent, Belgium.
⁸ School of Healthcare Sciences, Cardiff University, Wales, UK.
⁹ Rheumatology Unit, Department of Medicine and Public Health, AOU and University of Cagliari, Cagliari, Italy.
¹⁰ Axial Spondyloarthritis International Federation (ASIF), London, UK.
¹¹ Department of Rheumatology, Hôpital Cochin, University Paris Cité, Paris, France.
¹² PMR Department, Rheumatology Division, Marmara University School of Medicine, Istanbul, Turkey.
¹³ Department of Rheumatology, Cairo University, Cairo, Egypt.
¹⁴ Department of Rheumatology and Immunology, Singapore General Hospital, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
¹⁵ Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁶ Rheumatology Unit, Hospital Italiano de La Plata - Universidad Nacional de La Plata, La Plata, Argentina.
¹⁷ Health & Territory Research (HTR), Universidad de Sevilla, Seville, Spain.
¹⁸ Semmelweis University, Budapest, Hungary.
¹⁹ Division of Rheumatology, University of California San Francisco, San Francisco, CA, USA.
²⁰ Department of Rheumatology, Physical and Rehabilitation Medicine, Clinical University Centre, Sestre Milosrdnice, Zagreb, Croatia.
²¹ Department of Rheumatology and Immunology, Chinese PLA General Hospital, Beijing, China.
²² Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan.
²³ Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands; Department of Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands.
²⁴ Department of Rheumatology & Immunology, Singapore General Hospital, Duke-NUS Medical School, Singapore.
²⁵ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, UK; Department of Rheumatology, Division of Medicine, University College London, London, UK.
²⁶ NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
²⁷ Department of Rheumatology & Immunology, SVP Hospital & Smt. NHL Municipal Medical College, Ahmedabad, India; Department of Rheumatology, Marengo CIMS Hospital & RheumaCARE, Ahmedabad, India.
²⁸ Rheumatology Department Cochin Hospital, APHP, INSERM U-1153, Centre de Recherche en Epidémiologie et Statistiques, Université Paris Cité, Paris, France.
²⁹ Rheumatology Department, King's College Hospital, Centre for Rheumatic Diseases, Centre for Education, King's College London, London, UK.
³⁰ Department of Internal Medicine and Rheumatology, Klinikum Bielefeld, University of Bielefeld, Bielefeld, Germany.
³¹ Rheumalogy Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
³² Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; NOVA Medical School, UNL, Lisbon, Portugal.
³³ Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Department of Nursing, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
³⁴ Rheumazentrum Ruhrgebiet, Herne and Ruhr-University, Bochum, Germany.
³⁵ Department of Rheumatology, Leiden University, Leiden, The Netherlands.

PMID: 39955166
DOI: 10.1016/j.ard.2025.01.035

Free article

Review

The Assessment of SpondyloArthritis International Society (ASAS) Consensus-Based Expert Definition of Difficult-to-Manage, including Treatment-Refractory, Axial Spondyloarthritis

Denis Poddubnyy et al. Ann Rheum Dis. 2025 Apr.

Free article

. 2025 Apr;84(4):538-546.

doi: 10.1016/j.ard.2025.01.035. Epub 2025 Feb 14.

Authors

Affiliations

¹ Division of Rheumatology, Department of Medicine, University of Toronto and University Health Network, Toronto, ON, Canada; Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. Electronic address: denis.poddubnyy@uhn.ca.
² Department of Rheumatology, La Paz University Hospital, IdiPaz, Madrid, Spain.
³ Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁴ Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁵ Division of Rheumatology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada; Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁶ Centre for Human Movement and Rehabilitation, School of Health and Society, University of Salford, Salford, Greater Manchester, UK.
⁷ Department of Rheumatology, Ghent University, Ghent University Hospital, Ghent, Belgium.
⁸ School of Healthcare Sciences, Cardiff University, Wales, UK.
⁹ Rheumatology Unit, Department of Medicine and Public Health, AOU and University of Cagliari, Cagliari, Italy.
¹⁰ Axial Spondyloarthritis International Federation (ASIF), London, UK.
¹¹ Department of Rheumatology, Hôpital Cochin, University Paris Cité, Paris, France.
¹² PMR Department, Rheumatology Division, Marmara University School of Medicine, Istanbul, Turkey.
¹³ Department of Rheumatology, Cairo University, Cairo, Egypt.
¹⁴ Department of Rheumatology and Immunology, Singapore General Hospital, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
¹⁵ Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁶ Rheumatology Unit, Hospital Italiano de La Plata - Universidad Nacional de La Plata, La Plata, Argentina.
¹⁷ Health & Territory Research (HTR), Universidad de Sevilla, Seville, Spain.
¹⁸ Semmelweis University, Budapest, Hungary.
¹⁹ Division of Rheumatology, University of California San Francisco, San Francisco, CA, USA.
²⁰ Department of Rheumatology, Physical and Rehabilitation Medicine, Clinical University Centre, Sestre Milosrdnice, Zagreb, Croatia.
²¹ Department of Rheumatology and Immunology, Chinese PLA General Hospital, Beijing, China.
²² Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan.
²³ Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands; Department of Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands.
²⁴ Department of Rheumatology & Immunology, Singapore General Hospital, Duke-NUS Medical School, Singapore.
²⁵ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, UK; Department of Rheumatology, Division of Medicine, University College London, London, UK.
²⁶ NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
²⁷ Department of Rheumatology & Immunology, SVP Hospital & Smt. NHL Municipal Medical College, Ahmedabad, India; Department of Rheumatology, Marengo CIMS Hospital & RheumaCARE, Ahmedabad, India.
²⁸ Rheumatology Department Cochin Hospital, APHP, INSERM U-1153, Centre de Recherche en Epidémiologie et Statistiques, Université Paris Cité, Paris, France.
²⁹ Rheumatology Department, King's College Hospital, Centre for Rheumatic Diseases, Centre for Education, King's College London, London, UK.
³⁰ Department of Internal Medicine and Rheumatology, Klinikum Bielefeld, University of Bielefeld, Bielefeld, Germany.
³¹ Rheumalogy Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
³² Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; NOVA Medical School, UNL, Lisbon, Portugal.
³³ Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Department of Nursing, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
³⁴ Rheumazentrum Ruhrgebiet, Herne and Ruhr-University, Bochum, Germany.
³⁵ Department of Rheumatology, Leiden University, Leiden, The Netherlands.

PMID: 39955166
DOI: 10.1016/j.ard.2025.01.035

Abstract

Objectives: To develop a consensus-based expert definition of difficult-to-manage (D2M) axial spondyloarthritis (axSpA), incorporating treatment-refractory (TR) disease.

Methods: A literature review was conducted in 2022 to identify potential definitions for D2M/TR axSpA from prior studies, followed by a 2-round Delphi consensus process conducted in 2022 and 2023 to identify components of D2M axSpA. Based on the results of the Delphi process, a draft of the D2M axSpA definition was developed and presented to the expert task force, including patient representation, and, subsequently, to the Assessment of SpondyloArthritis International Society (ASAS) membership for endorsement in January 2024.

Results: Consensus was reached on a D2M definition encapsulating treatment failure (treatment according to the ASAS-European Alliance of Associations for Rheumatology recommendations and failure of ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs with different mechanisms of action unless contraindicated), suboptimal disease control, and physician or patient acknowledgement of problematic signs/symptoms in patients diagnosed with axSpA by the rheumatologist. This definition represents a broad concept that includes various reasons that lead to an unsatisfactory treatment outcome. TR axSpA is covered by the D2M definition but requires a history of treatment failure, the presence of objective signs of inflammatory activity, and the exclusion of noninflammatory reasons for nonresponse. The proposed D2M definition incorporating TR disease was endorsed by ASAS at the annual meeting in January 2024, with 89% votes (109/123) in favour of it.

Conclusions: The ASAS D2M axSpA definition, including TR disease, allows for identifying patients with unmet needs, paving the way for further research in this condition and its clinical care improvement.

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Conflict of interest statement

Competing interests DP has received research support from AbbVie, Eli Lilly, MSD, Novartis, Pfizer, consulting fees from AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, and UCB, and speaker fees from AbbVie, Canon, DKSH, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer, and UCB. DP is a member of the executive committee of ASAS. VN-C has received consultancy/speaker/research grants from AbbVie, Alphasigma, BMS, Fresenius Kabi, Galapagos, Janssen, Eli Lilly, Moonlake, MSD, Novartis, Pfizer, Roche, and UCB. VN-C is a member of the executive committee, executive secretary, and elected president of ASAS. MT: none declared. SA has received consulting fees from Argenx, Bristol-Myers Squibb, Galapagos, and Novartis. SZA has received grants from AbbVie, Eli Lilly, Jannsen, Novartis, Pfizer, and UCB, consulting fees from AbbVie, Eli Lilly, Jannsen, Novartis, Pfizer, and UCB, and honoraria from AbbVie, Eli Lilly, Jannsen, Novartis, Pfizer, and UCB. SB: none declared. FvdB: none declared. CB has received financial support from Novartis, AbbVie, Galapagos, Novartis, Pfizer, and UCB. AC has received grant support from BMS, Lilly, and Novartis, honoraria from Alfa Sigma, AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Novartis, Pfizer, and UCB, and travel/meeting attendance support from AbbVie and UCB. JD: none declared. MD has received grant support from Pfizer, UCB, and AbbVie, consulting fees from Novartis and Pfizer, travel/meeting attendance support from Novartis, and participation on a Data Safety Monitoring Board or Advisory Board for Galapagos. TD has received honoraria from AbbVie, Amgen, Novartis, Koçak, and Lilly and travel/meeting attendance support from Celltrion, Lilly, AbbVie, Amgen, Novartis, and Nobel. BE-Z has received consultancy, research grants, and speaker's honoraria from AbbVie, Amgen, BMS, Eva, Hekma, Janssen, Lilly, MSD, New Bridge, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier, and Sobi. WF has received speaker/consulting fees/grants from Novartis, Janssen and Janssen, GlaxoSmithKline, and Diethelm Keller Siber Hegner (DKSH). FvG has received consulting and speaker fees from AbbVie, ASAS, BMS, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB. RG-S has received consultancy/speaker/research grants from AbbVie, BMS, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, GSK, Biogen, Amgen, Raffo, and Adium. MGC has received grant support and travel/meeting attendance support from Novartis. PG: none declared. LG: none declared. SG has received honoraria from AbbVie, Altamedics, Amgen, Eli Lilly, Johnson & Johnson, Krka, Medis, MSD, Novartis, Pfizer, Sandoz, Sobi, Stada, Viatris, Teva, and Zentiva and support for attending meetings/travel from AbbVie, Novartis, and Pfizer. FH: none declared. MK has received honoraria from AbbVie, Amgen, Asahi-Kasei Pharma, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Novartis, Ono Pharma, Tanabe-Mitsubishi, and UCB Pharm. RL has received consulting fees from AbbVie, Pfizer, UCB, Eli Lilly, Novartis, Jansen Pharma, and Galapagos, honoraria from UCB and AbbVie, participated in a DSMB for a UCB trial, is ASAS and METEOR board member and director of Joint Imaging BV, and of Rheumatology Consultancy BV. YYL has received speaking fees from AbbVie, DKSH, Janssen, Novartis, and Pfizer. PMM has received honoraria from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme Pfizer, Roche, and UCB. HM-O has received research grants from Janssen, Novartis, Pfizer, and UCB and speaker fees/honoraria from AbbVie, Amgen, Biogen, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, and UCB. BM has received honoraria/participated in advisory boards and/or received speaker fees from IPCA, Cipla, Torrent, RPG Lifesciences, and Novartis. AM has received speaker honoraria/participated in advisory boards, and/or received research grants from Biogen, BMS, UCB, Pfizer, Johnson & Johnson, Novartis, Amgen, Gilead, Galapagos, AbbVie, Lilly, and Pfizer. EN has received speaker honoraria/participated in advisory boards, and/or received research grants from UCB, Pfizer, Gilead, Galapagos, AbbVie, Eli Lilly, Alfasigma, Fresenius, and Pfizer. SR has received research grants and/or consultancy fees from AbbVie, Eli Lilly, Galapagos/Alfasigma, Janssen, MSD, Novartis, Pfizer, Sanofi, and UCB. MR has received consulting and/or speaker fees from AbbVie, Chugai, Boehringer-Ingelheim, Eli Lilly, Janssen, Novartis, and UCB. CGSS has received consulting and speaker fees from AbbVie, Janssen, Novartis, and Pfizer. AS has received speaking and/or consulting fees from AbbVie, Novartis, UCB, and Lilly. Support for attending conferences: Janssen. JW has received research grants, speaker fees, or advisor board from Pfizer, Abbott, AbbVie, Bristol-Myers Squibb, Eli Lilly, JNJ, UCB, MSD, GSK, Chugai, Roche, Celgene, Sanofi-Aventis, and Novartis. XB has received research support from AbbVie, Eli Lilly, and Novartis, consulting fees from AbbVie, Alphasigma, BMS, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, and UCB, and speaker fees from AbbVie, Alphasigma, BMS, Eli Lilly, Janssen, Medscape, Novartis, Peervoice, Pfizer, and UCB. President of ASAS and EULAR. DvdH has received consulting fees from AbbVie, Alfasigma, Argenx, BMS, Eli Lilly, Grey-Wolf Therapeutics, Janssen, Novartis, Pfizer, Takeda, and UCB Pharma and is director of Imaging Rheumatology bv. DvdH is the associate editor of Annals Rheumatic Diseases, an editorial board member of the Journal of Rheumatology and RMD Open, and an advisor to Assessment of Axial Spondyloarthritis International Society.

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The Assessment of SpondyloArthritis International Society (ASAS) Consensus-Based Expert Definition of Difficult-to-Manage, including Treatment-Refractory, Axial Spondyloarthritis

Affiliations

The Assessment of SpondyloArthritis International Society (ASAS) Consensus-Based Expert Definition of Difficult-to-Manage, including Treatment-Refractory, Axial Spondyloarthritis

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Abstract

Conflict of interest statement

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