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Research ArticleArticle

One-Third of European Patients with Axial Spondyloarthritis Reach Pain Remission With Routine Care Tumor Necrosis Factor Inhibitor Treatment

Lykke Midtbøll Ørnbjerg, Kathrine Rugbjerg, Stylianos Georgiadis, Simon Horskjær Rasmussen, Ulf Lindström, Karel Pavelka, Neslihan Yilmaz, Ennio Giulio Favalli, Michael J. Nissen, Brigitte Michelsen, Elsa Vieira-Sousa, Gareth T. Jones, Ruxandra Ionescu, Heikki Relas, Carlos Sanchez-Piedra, Matija Tomšič, Arni Jon Geirsson, Irene van der Horst-Bruinsma, Johan Askling, Anne Gitte Loft, Lucie Nekvindova, Haner Direskeneli, Florenzo Iannone, Adrian Ciurea, Karen Minde Fagerli, Maria José Santos, Gary J. Macfarlane, Catalin Codreanu, Kari Eklund, Manuel Pombo-Suarez, Ziga Rotar, Bjorn Gudbjornsson, Tamara Rusman, Mikkel Østergaard and Merete Lund Hetland
The Journal of Rheumatology December 2022, jrheum.220459; DOI: https://doi.org/10.3899/jrheum.220459
Lykke Midtbøll Ørnbjerg
The European Spondyloarthritis Research Collaboration Network was financially supported by Novartis Pharma AG. Novartis had no influence on the data collection, statistical analyses, manuscript preparation, or decision to submit the manuscript. L.M. Ørnbjerg, MD, PhD, K. Rugbjerg, MSc, PhD, S. Georgiadis, PhD, S.H. Rasmussen, PhD, Copenhagen Center for Arthritis Research (COPECARE), Centre for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Copenhagen University Hospital, Glostrup, Denmark. U. Lindström, MD, PhD, Department of Rheumatology and Inflammation Research, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden. K. Pavelka, MD, PhD, Institute of Rheumatology, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic. N. Yilmaz, MD, Department of Rheumatology, Demiroglu Bilim University, Istanbul, Turkey. E.G. Favalli, MD, PhD, Division of Clinical Rheumatology, ASST Gaetano Pini-CTO Institute, Milan, Italy. M.J. Nissen, MD, PhD, Department of Rheumatology, Geneva University Hospital, Geneva, Switzerland. B. Michelsen, MD, PhD, Department of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway, and Division of Rheumatology, Department of Medicine, Hospital of Southern Norway Trust, Kristiansand, Norway, and COPECARE, Centre for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Copenhagen University Hospital, Glostrup, Denmark. E. Vieira-Sousa, MD, Department of Rheumatology, Hospital de Santa Maria, CHULN, Instituto Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisbon, Portugal. G.T. Jones, PhD, G.J. Macfarlane, MD, PhD, Aberdeen Centre for Arthritis and Musculoskeletal Health (Epidemiology Group), University of Aberdeen, Aberdeen, United Kingdom. R. Ionescu, MD, PhD, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. H. Relas, MD, PhD, K. Eklund, MD, PhD, Inflammation Center, Department of Rheumatology, Helsinki University Hospital, Helsinki, Finland. C. Sanchez-Piedra, MD, PhD, Research Unit, Spanish Society of Rheumatology, Madrid, Spain. M. Tomšič, MD, PhD, Z. Rotar, MD, PhD, Department of Rheumatology, University Medical Centre Ljubljana, and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. A.J. Geirsson, MD, Department of Rheumatology, University Hospital, Reykjavik, Iceland. I. van der Horst-Bruinsma, MD, PhD, Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands. J. Askling, MD, PhD, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. A.G. Loft, MD, PhD, Department of Rheumatology, Aarhus University Hospital, and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. L. Nekvindova, MD, PhD, Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, and Institute of Biostatistics and Analyses, Ltd., Brno, Czech Republic. H. Direskeneli, MD, Department of Rheumatology, Marmara University School of Medicine, Istanbul, Turkey. F. Iannone, MD, PhD, Rheumatology Unit, DETO, University of Bari, Italy. A. Ciurea, MD, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. K.M. Fagerli, MD, PhD, Department of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway. M.J. Santos, MD, PhD, Department of Rheumatology, Hospital Garcia de Orta, Almada, Portugal. C. Codreanu, MD, PhD, Center for Rheumatic Diseases, University of Medicine and Pharmacy, Bucharest, Romania. M. Pombo-Suarez, MD, PhD, Rheumatology Service, Hospital Clinico Universitario, Santiago de Compostela, Spain. B. Gudbjornsson, MD, PhD, Centre for Rheumatology Research, Landspitali University Hospital, and Faculty of Medicine, University of Iceland, Reykjavik, Iceland. T. Rusman, MSc, Department of Rheumatology, Amsterdam UMC, VU University Medical Centre, Amsterdam, the Netherlands. M. Østergaard, MD, PhD, DMSc, M.L. Hetland, MD, PhD, DMSc, COPECARE, Centre for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Copenhagen University Hospital, Glostrup, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. L.M. Ørnbjerg and K. Rugbjerg are co-first authors and contributed equally to this work. M. Østergaard and M.L. Hetland are co-senior authors and contributed equally to this work. KR, LMØ, SG, BM, and SHR each received a research grant paid to employer from Novartis. KP has received consulting and speaking fees from Roche, BMS, AbbVie, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Egis, Medac, Biogen. NY has received consultation fees from AbbVie, Novartis, Pfizer, and Johnson & Johnson. EGF has received speaker and consultation fees from Eli Lilly, MSD, Novartis, and Janssen. MJN has received speaker fees from AbbVie, Eli Lilly, MSD, and Novartis. EVS has received research grants from MSD, Pfizer, and UCB; and speaker fees from Novartis, AbbVie, MSD, Celgene, and UCB. GTJ has received speaker fees from Abbvie, Pfizer, UCB, Amgen (Celgene), and GSK. RI has received speaker fees from AbbVie, BI, BMS, Novartis, Sandoz, Pfizer, Eli Lilly, and Zentiva. HR has received congress fees and speaker fees from AbbVie, Celgene, and Pfizer. MT has received speaking and consulting fees from AbbVie, Amgen, Biogen, Eli Lilly, Janssen, Medias, Medis, MSD, Novartis, OPH Oktal Pharma, Sandoz, and Pfizer. IvdHB has received consulting fees from AbbVie, Lilly, Novartis, UCB, BMS, MSD, UCB, and Pfizer. JA is the principal investigator for agreements between AbbVie, AstraZeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, for the Antirheumatic Therapy in Sweden safety monitoring. AGL has received consulting and speaker fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB. HD has received research grants, educational travel support, speaker, and consulting fees from AbbVie, Pfizer, Roche, MSD, UCB, Amgen, Novartis, BMS, Celgene, and Abdiıbrahim. FI has received speaker/consultation fees from AbbVie, Roche, MSD, UCB, Lilly, Janssen, Sanofi, Pfizer, and Novartis. AC has received consulting and/or speaking fees from AbbVie, Eli Lilly, MSD, Novartis, and Pfizer. MJS has received speaker fees from AbbVie, Pfizer, and Novartis. GJM received a research grant from GSK. CC has received speaker and consulting fees from AbbVie, Amgen, Egis, Ewopharma, Lilly, Novartis, Pfizer, Roche, Sandoz, and UCB. KE has received consulting fees from Amgen, Celgene, Gilag, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sobi, and UCB. MPS has received consulting fees from AbbVie, MSD, and Roche. ZR has received speaker and consultation fees from AbbVie, Amgen, BI, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB. BG has received speaker fees from Novartis and Amgen. MØ received research grants from AbbVie, BMS, Merck, Celgene, and Novartis; and speaker and/or consulting fees from AbbVie, BMS, BI, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB. MLH received research grants from AbbVie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics BV, Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, and Novartis. The remaining authors declare no conflicts of interest relevant to this article. Address correspondence to Dr. L.M. Ørnbjerg, COPECARE, Rigshospitalet, Valdemar Hansens Vej 17, 2600 Glostrup, Denmark. Email: lykke.midtboell. oernbjerg@regionh.dk. Accepted for publication October 13, 2022.
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Kathrine Rugbjerg
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Stylianos Georgiadis
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Simon Horskjær Rasmussen
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Ulf Lindström
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Karel Pavelka
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Neslihan Yilmaz
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Ennio Giulio Favalli
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Michael J. Nissen
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Brigitte Michelsen
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Elsa Vieira-Sousa
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Gareth T. Jones
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Ruxandra Ionescu
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Heikki Relas
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Carlos Sanchez-Piedra
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Matija Tomšič
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Arni Jon Geirsson
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Irene van der Horst-Bruinsma
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Johan Askling
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Anne Gitte Loft
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Lucie Nekvindova
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Haner Direskeneli
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Florenzo Iannone
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Adrian Ciurea
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Karen Minde Fagerli
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Maria José Santos
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Gary J. Macfarlane
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Catalin Codreanu
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Kari Eklund
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Manuel Pombo-Suarez
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Ziga Rotar
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Bjorn Gudbjornsson
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Tamara Rusman
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Mikkel Østergaard
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Merete Lund Hetland
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Abstract

Objective To investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA).

Methods Fifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment.

Results Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/ 6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi.

Conclusion Patients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

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One-Third of European Patients with Axial Spondyloarthritis Reach Pain Remission With Routine Care Tumor Necrosis Factor Inhibitor Treatment
Lykke Midtbøll Ørnbjerg, Kathrine Rugbjerg, Stylianos Georgiadis, Simon Horskjær Rasmussen, Ulf Lindström, Karel Pavelka, Neslihan Yilmaz, Ennio Giulio Favalli, Michael J. Nissen, Brigitte Michelsen, Elsa Vieira-Sousa, Gareth T. Jones, Ruxandra Ionescu, Heikki Relas, Carlos Sanchez-Piedra, Matija Tomšič, Arni Jon Geirsson, Irene van der Horst-Bruinsma, Johan Askling, Anne Gitte Loft, Lucie Nekvindova, Haner Direskeneli, Florenzo Iannone, Adrian Ciurea, Karen Minde Fagerli, Maria José Santos, Gary J. Macfarlane, Catalin Codreanu, Kari Eklund, Manuel Pombo-Suarez, Ziga Rotar, Bjorn Gudbjornsson, Tamara Rusman, Mikkel Østergaard, Merete Lund Hetland
The Journal of Rheumatology Dec 2022, jrheum.220459; DOI: 10.3899/jrheum.220459

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One-Third of European Patients with Axial Spondyloarthritis Reach Pain Remission With Routine Care Tumor Necrosis Factor Inhibitor Treatment
Lykke Midtbøll Ørnbjerg, Kathrine Rugbjerg, Stylianos Georgiadis, Simon Horskjær Rasmussen, Ulf Lindström, Karel Pavelka, Neslihan Yilmaz, Ennio Giulio Favalli, Michael J. Nissen, Brigitte Michelsen, Elsa Vieira-Sousa, Gareth T. Jones, Ruxandra Ionescu, Heikki Relas, Carlos Sanchez-Piedra, Matija Tomšič, Arni Jon Geirsson, Irene van der Horst-Bruinsma, Johan Askling, Anne Gitte Loft, Lucie Nekvindova, Haner Direskeneli, Florenzo Iannone, Adrian Ciurea, Karen Minde Fagerli, Maria José Santos, Gary J. Macfarlane, Catalin Codreanu, Kari Eklund, Manuel Pombo-Suarez, Ziga Rotar, Bjorn Gudbjornsson, Tamara Rusman, Mikkel Østergaard, Merete Lund Hetland
The Journal of Rheumatology Dec 2022, jrheum.220459; DOI: 10.3899/jrheum.220459
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