OBJECTIVE: To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with (i) treatment line (second and third TNFi-series) and (ii) reason for withdrawal from the preceding TNFi [lack of efficacy (LOE) vs 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 vs 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 vs ≥26 weeks) (58% vs 71%, P < 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) vs LOE (17%), P < 0.001, while similar for the third TNFi (19% vs 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 vs LOE.

Center for Rheumatology and Spine Diseases Center for Head and Orthopaedics Copenhagen Center for Arthritis Research Rigshospitalet Glostrup Denmark

Center for treatment of Rheumatic and Musculoskeletal Diseases Diakonhjemmet Hospital Oslo Norway

Centre for Rheumatology Research Landspitali University Hospital Reykjavik Iceland and Faculty of Medicine University of Iceland Reykjavik Iceland

Clinical Epidemiology Division Department of Medicine Solna Karolinska Institutet Stockholm Sweden

DANBIO Registry Center for Rheumatology and Spine Diseases Center for Head and Orthopaedics Rigshospitalet Glostrup Denmark

Department of Clinical Medicine University of Copenhagen Copenhagen Denmark

Department of Clinical Sciences Lund Rheumatology Skåne University Hospital Lund University Lund Sweden

Department of Internal Medicine Dermatology and Psychiatry Universidad de La Laguna and Rheumatology Service Hospital Universitario de Canarias La Laguna Spain

Department of Rheumatology Centro Hospitalar do Baixo Vouga Aveiro and Comprehensive Health Research Centre NOVA Medical School Universidade Nova de Lisboa Lisbon Portugal

Department of Rheumatology Geneva University Hospital Geneva Switzerland

Department of Rheumatology Hospital Garcia de Orta Almada and Instituto Medicina Molecular Faculdade de Medicina da Universidade de Lisboa Lisbon Portugal

Department of Rheumatology Hospital General Universitario Gregorio Marañón and Faculty of Medicine Complutense University of Madrid Madrid Spain

Department of Rheumatology University Hospital Reykjavik Iceland

Department of Rheumatology University Hospital Zurich University of Zurich Zurich Switzerland

Department of Rheumatology University Medical Centre Ljubljana and Faculty of Medicine University of Ljubljana Ljubljana Slovenia

Departments of Medicine and Rheumatology Helsinki University Hospital Helsinki Finland

Inflammation Center Department of Rheumatology Helsinki University Hospital Helsinki Finland

Institute of Rheumatology and Department of Rheumatology 1st Faculty of Medicine Charles University Prague Czech Republic

Research Unit Sørlandet Hospital Kristiansand Norway

School of Medicine Department of Internal Medicine Division of Rheumatology Izmir Katip Celebi University Izmir Turkey

Zitelab ApS Copenhagen Denmark

See more in PubMed

Van Der Heijde D, Dijkmans B, Geusens P. et al.; Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy Study Group. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 2005;52:582–91. PubMed

Van Der Heijde D, Kivitz A, Schiff MH. et al.; ATLAS Study Group. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2006;54:2136–46. PubMed

Juanola X, Ramos MJM, Belzunegui JM, Fernández-Carballido C, Gratacós J.. Treatment failure in axial spondyloarthritis: insights for a standardized definition. Adv Ther 2022;39:1490–501. PubMed PMC

Glintborg B, Østergaard M, Krogh NS. et al. Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years’ surveillance in the Danish nationwide DANBIO registry. Ann Rheum Dis 2010;69:2002–8. PubMed

Baraliakos X, Braun J, Deodhar A. et al. Long-term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis: 5-year results from the phase III MEASURE 1 extension study. RMD open 2019;5:e001005. PubMed PMC

Baeten D, Sieper J, Braun J. et al.; MEASURE 2 Study Group. Secukinumab, an interleukin-17a inhibitor, in ankylosing spondylitis. N Engl J Med 2015;373:2534–48. PubMed

Lie E, Van Der Heijde D, Uhlig T. et al. Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register. Ann Rheum Dis 2011;70:157–63. PubMed

Rudwaleit M, Van den Bosch F, Kron M, Kary S, Kupper H.. Effectiveness and safety of adalimumab in patients with ankylosing spondylitis or psoriatic arthritis and history of anti-tumor necrosis factor therapy. Arthritis Res Ther 2010;12:R117. PubMed PMC

Glintborg B, Østergaard M, Krogh NS. et al. Clinical response, drug survival and predictors thereof in 432 ankylosing spondylitis patients after switching tumour necrosis factor α inhibitor therapy: results from the Danish nationwide DANBIO registry. Ann Rheum Dis 2013;72:1149–55. PubMed

Heinonen AV, Aaltonen KJ, Joensuu JT. et al. Effectiveness and drug survival of TNF inhibitors in the treatment of ankylosing spondylitis: a prospective cohort study. J Rheumatol 2015;42:2339–46. PubMed

Navarro-Compán V, Plasencia-Rodríguez C, de Miguel E. et al. Switching biological disease-modifying antirheumatic drugs in patients with axial spondyloarthritis: results from a systematic literature review. RMD Open 2017;3:e000524. PubMed PMC

Deodhar A, Yu D.. Switching tumor necrosis factor inhibitors in the treatment of axial spondyloarthritis. Semin Arthritis Rheum 2017;47:343–50. PubMed

Ciurea A, Exer P, Weber U. et al.; Rheumatologists of Swiss Clinical Quality Management Program for Axial Spondyloarthritis. Does the reason for discontinuation of a first TNF inhibitor influence the effectiveness of a second TNF inhibitor in axial spondyloarthritis? Results from the Swiss Clinical Quality Management Cohort. Arthritis Res Ther 2016;18:71. PubMed PMC

Manica SR, Sepriano A, Pimentel-Santos F. et al. Effectiveness of switching between TNF inhibitors in patients with axial spondyloarthritis: is the reason to switch relevant? Arthritis Res Ther 2020;22:195. PubMed PMC

Karlsson JA, Kristensen LE, Kapetanovic MC. et al. Treatment response to a second or third TNF-inhibitor in RA: results from the South Swedish Arthritis Treatment Group Register. Rheumatology (Oxford) 2008;47:507–13. PubMed

Ward MM, Deodhar A, Gensler LS. et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol 2019;71:1599–613. PubMed PMC

Ramiro S, Nikiphorou E, Sepriano A. et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis 2023;82:19–34. PubMed

Brahe CH, Ørnbjerg LM, Jacobsson L. et al. Retention and response rates in 14 261 PsA patients starting TNF inhibitor treatment - Results from 12 countries in EuroSpA. Rheumatol (United Kingdom) 2020;59:1640–50. PubMed

Ørnbjerg LM, Brahe CH, Askling J. et al. Treatment response and drug retention rates in 24 195 biologic-naïve patients with axial spondyloarthritis initiating TNFi treatment: routine care data from 12 registries in the EuroSpA collaboration. Ann Rheum Dis 2019;78:1536–44. PubMed

Jenkinson TR, Mallorie PA, Whitelock HC. et al. Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. J Rheumatol 1994;21:1694–8. PubMed

Calin A, Garrett S, Whitelock H, O’Hea J, Jenkinson MP.. T. A new approach to defining functional ability in ankylosing spondylitis: the development of the bath ankylosing spondylitis functional index. J Rheumatol 1994;21:2281–5. PubMed

Lukas C, Landewé R, Sieper J. et al.; Assessment of SpondyloArthritis international Society. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009;68:18–24. PubMed

Garrett S, Jenkinson T, Kennedy LG. et al. A new approach to defining disease status in ankylosing spondylitis: the bath ankylosing spondylitis disease activity index. J Rheumatol 1994;21:2286–91. PubMed

Ward MM, Deodhar A, Gensler LS. et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol (Hoboken, NJ) 2019;71:1599–613. PubMed PMC

Kristensen LE, Saxne T, Geborek P.. The LUNDEX, a new index of drug efficacy in clinical practice: results of a five-year observational study of treatment with infliximab and etanercept among rheumatoid arthritis patients in Southern Sweden. Arthritis Rheum 2006;54:600–6. PubMed

Dadoun S, Geri G, Paternotte S, Dougados M, Gossec L.. Switching between tumour necrosis factor blockers in spondyloarthritis: a retrospective monocentre study of 222 patients. Clin Exp Rheumatol 2011;29:1010–3. PubMed

Anderson JJ, Baron G, Van Der Heijde D, Felson DT, Dougados M.. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum 2001;44:1876–86. PubMed

Christiansen SN, Ørnbjerg LM, Rasmussen SH. et al. European bio-naïve spondyloarthritis patients initiating TNFi: time trends in baseline characteristics, treatment retention and response. Rheumatology (Oxford) 2022;61:3799–807. PubMed

van der Heijde D, Cheng-Chung Wei J, Dougados M. et al.; COAST-V Study Group. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 ra. Lancet (London, England) 2018;392:2441–51. PubMed

Deodhar A, Poddubnyy D, Pacheco-Tena C. et al.; COAST-W Study Group. Efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthritis: sixteen-week results from a phase III randomized, double-blind, placebo-controlled trial in patients with prior inadequate response to or intolerance of tumor necr. Arthritis Rheumatol 2019;71:599–611. PubMed PMC

Michelsen B, Lindström U, Codreanu C. et al. Drug retention, inactive disease and response rates in 1860 patients with axial spondyloarthritis initiating secukinumab treatment: routine care data from 13 registries in the EuroSpA collaboration. RMD Open 2020;6:e001280. PubMed PMC

Chimenti MS, Fonti GL, Conigliaro P. et al. One-year effectiveness, retention rate, and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a real-life multicenter study. Expert Opin Biol Ther 2020;20:813–21. PubMed

Ramonda R, Lorenzin M, Carriero A. et al.; on behalf Spondyloartritis and Psoriatic Arthritis SIR Study Group “Antonio Spadaro”. Effectiveness and safety of secukinumab in 608 patients with psoriatic arthritis in real life: a 24-month prospective, multicentre study. RMD Open 2021;7:e001519. PubMed PMC