Second and third TNF inhibitors in European patients with axial spondyloarthritis: Effectiveness and impact of the reason for switching

Louise Linde; Lykke Midtbøll Ørnbjerg; Cecilie Heegaard Brahe; Johan Karlsson Wallman; Daniela Di Giuseppe; Jakub Závada; Isabel Castrejon; Federico Díaz-Gonzalez; Ziga Rotar; Matija Tomšič; Bente Glintborg; Bjorn Gudbjornsson; Arni Jon Geirsson; Brigitte Michelsen; Eirik Klami Kristianslund; Maria José Santos; Anabela Barcelos; Dan Nordström; Kari K Eklund; Adrian Ciurea; Michael Nissen; Servet Akar; Lise Hejl Hyldstrup; Niels Steen Krogh; Merete Lund Hetland; Mikkel Østergaard

doi:10.1093/rheumatology/kead494

Second and third TNF inhibitors in European patients with axial spondyloarthritis: Effectiveness and impact of the reason for switching

Rheumatology (Oxford). 2023 Sep 20:kead494. doi: 10.1093/rheumatology/kead494. Online ahead of print.

Authors

Louise Linde^{1

2}, Lykke Midtbøll Ørnbjerg^{1

2}, Cecilie Heegaard Brahe¹, Johan Karlsson Wallman³, Daniela Di Giuseppe⁴, Jakub Závada⁵, Isabel Castrejon⁶, Federico Díaz-Gonzalez⁷, Ziga Rotar⁸, Matija Tomšič⁸, Bente Glintborg^{1

2

9}, Bjorn Gudbjornsson¹⁰, Arni Jon Geirsson¹¹, Brigitte Michelsen^{1

12

13}, Eirik Klami Kristianslund¹², Maria José Santos¹⁴, Anabela Barcelos¹⁵, Dan Nordström¹⁶, Kari K Eklund¹⁷, Adrian Ciurea¹⁸, Michael Nissen¹⁹, Servet Akar²⁰, Lise Hejl Hyldstrup¹, Niels Steen Krogh²¹, Merete Lund Hetland^{1

9}, Mikkel Østergaard^{1

9}

Affiliations

¹ Center for Rheumatology and Spine Diseases, Center for Head and Orthopaedics, Copenhagen Center for Arthritis Research (COPECARE), Rigshospitalet, Glostrup, Denmark.
² DANBIO Registry, Center for Rheumatology and Spine Diseases, Center for Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark.
³ Department of Clinical Sciences Lund, Rheumatology, Skåne University Hospital, Lund University, Lund, Sweden.
⁴ Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
⁵ Institute of Rheumatology and Department of Rheumatology, 1 Faculty of Medicine, Charles University, Prague, Czech Republic.
⁶ Department of Rheumatology, Hospital General Universitario Gregorio Marañón and Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
⁷ Department of Internal Medicine, Dermatology and Psychiatry, Universidad de La Laguna and Rheumatology Service, Hospital Universitario de Canarias, La Laguna, Spain.
⁸ Department of Rheumatology, University Medical Centre Ljubljana and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
⁹ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Centre for Rheumatology Research (ICEBIO), Landspitali University Hospital, Reykjavik, Iceland and Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
¹¹ Department of Rheumatology, University Hospital, Reykjavik, Iceland.
¹² Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway.
¹³ Research Unit, Sørlandet Hospital, Kristiansand, Norway.
¹⁴ Department of Rheumatology, Hospital Garcia de Orta, Almada and Instituto Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal; Reuma.pt registry.
¹⁵ Department of Rheumatology, Centro Hospitalar do Baixo Vouga, Aveiro and Comprehensive Health Research Centre, NOVA Medical School, Universidade Nova de Lisboa. Lisbon, Portugal: Reuma.pt registry.
¹⁶ Departments of Medicine and Rheumatology, Helsinki University Hospital, Helsinki, Finland.
¹⁷ Inflammation Center, Department of Rheumatology, Helsinki University Hospital, Helsinki, Finland.
¹⁸ Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
¹⁹ Department of Rheumatology, Geneva University Hospital, Geneva, Switzerland.
²⁰ School of Medicine, Department of Internal Medicine, Division of Rheumatology, Izmir Katip Celebi University, Izmir, Turkey.
²¹ Zitelab ApS, Copenhagen, Denmark.

PMID: 37738257
DOI: 10.1093/rheumatology/kead494

Abstract

Objective: To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with 1) treatment line (second and third TNFi-series) and 2) reason for withdrawal from the preceding TNFi (lack of efficacy (LOE) versus adverse events (AE)).

Methods: Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission (Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)) were assessed in second and third TNFi-series and stratified by withdrawal reason.

Results: We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE versus LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE < 26 versus ≥26 weeks) (58% versus 71%, p< 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) versus LOE (17%), p< 0.001, while similar for the third TNFi (19% versus 13%, p= 0.20).

Conclusion: A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE versus LOE.

Keywords: Axial spondyloarthritis; adverse events; effectiveness; lack of efficacy; switching TNF-inhibitors.