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Original research
Sex differences in the effectiveness of first-line tumour necrosis factor inhibitors in axial spondyloarthritis: results from the EuroSpA Research Collaboration Network
  1. Pasoon Hellamand1,2,
  2. Marleen van de Sande1,2,
  3. Lykke MIdtbøll Ørnbjerg3,
  4. Thomas Klausch4,
  5. Michael T Nurmohamed2,
  6. Ronald F van Vollenhoven1,2,
  7. Dan Nordström5,
  8. Anna Mari Hokkanen6,
  9. Maria Jose Santos7,8,
  10. Elsa Vieira-Sousa8,9,
  11. Anne G Loft10,11,
  12. Bente Glintborg3,12,
  13. Merete Lund Hetland12,13,
  14. Ulf Lindström14,
  15. Johan K Wallman15,
  16. Brigitte Michelsen16,17,
  17. Eirik Klami Kristianslund16,
  18. Adrian Ciurea18,
  19. Michael S Nissen19,
  20. Catalin Codreanu20,
  21. Corina Mogosan20,
  22. Gary J Macfarlane21,
  23. Ovidiu Rotariu21,
  24. Ziga Rotar22,23,
  25. Matija Tomšič22,23,
  26. Isabel Castrejon24,25,
  27. Lucia Otero-Varela26,
  28. Bjorn Gudbjornsson27,28,
  29. Arni Jon Geirsson29,
  30. Jiří Vencovský30,31,
  31. Karel Pavelka30,31,
  32. Semih Gulle32,
  33. Berrin Zengin32,
  34. Florenzo Iannone33,
  35. Rosario Foti34,
  36. Mikkel Ostergaard12,35 and
  37. Irene van der Horst-Bruinsma36
  1. 1Department of Rheumatology and Clinical Immunology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
  2. 2Amsterdam Rheumatology and Immunology Center (ARC), Reade and Amsterdam UMC, Amsterdam, The Netherlands
  3. 3Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark
  4. 4Department of Epidemiology and Data Science, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands
  5. 5Departments of Medicine and Rheumatology, Helsinki University Central Hospital, Helsinki, Finland
  6. 6Department of Medicine, Helsinki University and Helsinki University Hospital, Helsinki, Finland
  7. 7Department of Rheumatology, Hospital Garcia de Orta EPE, Almada, Portugal
  8. 8Faculdade de Medicina da Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Instituto Medicina Molecular, Lisbon, Portugal
  9. 9Department of Rheumatology, Hospital de Santa Marta, Lisbon, Portugal
  10. 10Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark
  11. 11Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  12. 12Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  13. 13Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Rigshospitalet, Denmark
  14. 14Department of Rheumatology and Inflammation Research, University of Gothenburg Sahlgrenska Academy, Goteborg, Sweden
  15. 15Department of Clinical Sciences Lund, Rheumatology, Skåne University Hospital, Lund University, Lund, Sweden
  16. 16Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway
  17. 17Research Unit, Sørlandet Hospital, Kristiansand, Norway
  18. 18Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
  19. 19Department of Rheumatology, Geneva University Hospitals, Geneve, Switzerland
  20. 20Center for Rheumatic Diseases, University of Medicine and Pharmacy, Bucuresti, Romania
  21. 21Aberdeen Centre for Arthritis and Musculoskeletal Health (Epidemiology Group), University of Aberdeen, Aberdeen, UK
  22. 22Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia
  23. 23Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
  24. 24Department of Rheumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
  25. 25Faculty of Medicine, Complutense University, Madrid, Spain
  26. 26Research Unit, Spanish Society of Rheumatology, Madrid, Spain
  27. 27Centre for Rheumatology Research, Landspitali University Hospital, Reykjavik, Iceland
  28. 28Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  29. 29Department of Rheumatology, University Hospitali, Reykjavik, Iceland
  30. 30Department of Rheumatology, Institute of Rheumatology, Prague, Czech Republic
  31. 31First Faculty of Medicine, Charles University, Prague, Czech Republic
  32. 32Division of Rheumatology, Department of Internal Medicine, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey
  33. 33Rheumatology Unit, DiMePReJ, University of Bari, Bari, Italy
  34. 34Division of Reumathology, A.O.U. "Policlinico-San Marco", Catania, Italy
  35. 35Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Copenhagen, Denmark
  36. 36Department of Rheumatology, Radboudumc, Nijmegen, Netherlands
  1. Correspondence to Professor Irene van der Horst-Bruinsma; Irene.vanderHorst-Bruinsma{at}radboudumc.nl

Abstract

Objective Evidence indicates reduced treatment effectiveness of TNFi in women with axial spondyloarthritis (axSpA) compared with men. We aimed to investigate sex differences in treatment response and retention rates over 24 months of follow-up in axSpA patients initiating their first TNFi.

Methods Data from axSpA patients initiating a TNFi in 1 of 15 registries within EuroSpA collaboration were pooled. We investigated the association of sex with treatment response using logistic regression. The primary outcome was clinically important improvement (CII) at 6 months according to Ankylosing Spondylitis Disease Activity Score with C-reactive protein (CRP) (≥1.1 decrease). We adjusted for age, country and TNFi start year. A secondary outcome was retention rates over 24 months of follow-up assessed by Kaplan-Meier estimator.

Results In total, 6451 axSpA patients with data on CII were assessed for treatment response; 2538 (39%) were women and 3913 (61%) were men. Women presented at baseline with lower CRP levels but had higher scores on patient-reported outcome measures. At 6 months, 53% of the women and 66% of the men had CII. Women had a lower relative risk of CII compared with men (0.81; 95% CI 0.77 to 0.84). This sex difference was similar in adjusted analysis (0.85; 95% CI 0.82 to 0.88). Retention rates were evaluated in 27 702 patients. The TNFi 6/12/24 months retention rates were significantly lower among women (79%/66%/53%) than men (88%/79%/69%).

Conclusion Treatment response and retention rates are lower among women with axSpA initiating their first TNFi. Sex differences in treatment effectiveness were present regardless of the outcome measure used for treatment response, and differences in retention rates transpired early and increased as time progressed.

  • ankylosing spondylitis
  • spondylitis, ankylosing
  • tumor necrosis factor inhibitors
  • biological therapy
  • epidemiology

Data availability statement

No data are available. Data are not available to external researchers for logistical reasons. It would require permissions from each contributing registry, plus access to the secure server in Copenhagen. Queries about the data contained in this manuscript can be addressed by reasonable request to the corresponding author.

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This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Data availability statement

No data are available. Data are not available to external researchers for logistical reasons. It would require permissions from each contributing registry, plus access to the secure server in Copenhagen. Queries about the data contained in this manuscript can be addressed by reasonable request to the corresponding author.

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Footnotes

  • Twitter @UAberdeenEpi

  • Contributors See online supplemental table S7A for contributorship per author. IvdHB is responsible for the overall content as a guarantor and controlled the decision to publish. All authors agreed on the final content of the submitted manuscript.

  • Funding The EuroSpA Research Collaboration Network was financially supported by Novartis Pharma AG.

  • Disclaimer Novartis had no influence on the data collection, statistical analyses, manuscript preparation or decision to submit the manuscript.

  • Competing interests PH: Research grant from Novartis (paid to employer). MvdS: Research grant and/or consulting fee, and/or speaker fee from Eli Lilly, Novartis, UCB, Janssen and Abbvie. LMO: Research grant from Novartis. TK: None. MTN: None. RFvV: Research support (institutional grants) from BMS and UCB. Support for educational programs (institutional grants) from MSD, Novartis, Pfizer, Roche, Sanofi, and UCB. Consultancy grants from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Pfizer, and UCB. Speaker grant from AbbVie, AstraZeneca, BMS, Galapagos, GSK, Janssen, Pfizer and UCB. DN: Consulting fees from Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB. Speakers fees from Novartis, Pfizer and UCB. Research grant from MSD. AMH: Research grant from MSD. MJS: Speaker fees from Abbvie, AstraZeneca, Lilly, Novartis and Pfizer. EV-S: Speaker fees from Novartis, Abbvie, MSD, Celgene and UCB. Research grants from MSD, Pfizer and UCB. AGL: Speaking and/or consulting fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB. Research grant from Novartis. BG: Research grants from Pfizer, Abbvie, BMS, Sandoz. MLH: Speaker for Pfizer, Medac and Sandoz. Research grants from Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis. UL: None. JKW: Speaker fees from AbbVie, and Amgen. Research support from AbbVie, Amgen, Eli Lilly, Novartis and Pfizer. BM: Research grant from Novartis (paid to employer). EKK: None. AC: Consulting and/or speaking fees from AbbVie and Novartis. MSN: Consulting and/or speaking fees from AbbVie, Eli Lilly, Janssens, Novartis and Pfizer. CC: Speaker and consultancy fees from AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, and Pfizer. CM: Speaker fees from AbbVie, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, and Pfizer. GJM: Research grant from GSK. OR: None. ZR: Consultant fees from Abbvie, Novartis, Eli Lilly, Pfizer, and Janssen. Speakers fees from Abbvie, Amgen, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek and Janssen. MT: Consulting and/or speaking fees from Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi and Sandoz-Lek. IC: Speaker and/or consultancy fees from BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, MSD, Pfizer and GSK. LO-V: None. BG: Consulting fees from Novartis. Speaking fees from Novartis and Nordic-Pharma. AJG: None. JV: Consultant fees from Abbvie, Argenx, Boehringer, Eli Lilly, Gilead, Octapharma, Pfizer and UCB. Speakers fees from Abbvie, Biogen, Boehringer, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, UCB and Werfen. Research grant from Abbvie. KP: Consultant fees for AbbVie, UCB, Pfizer, Eli Lilly, Celltrion, MSD and Novartis. SG: None. BZ: None. FI: Consulting and/or speaking from Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB. Research grant from BMS, Galapagos and Pfizer. RF: None. MO: Speaker and/or consultancy fees from Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB. Research grants from Abbvie, BMS, Merck, Novartis and UCB. IvdH-B: Consultant for Abbvie, UCB, MSD, Novartis and Lilly. Fees received for lectures from BMS, AbbVie, Pfizer and MSD. Unrestricted Grants received for investigator initiated studies from MSD, Pfizer, AbbVie and UCB.

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