Sex differences in the effectiveness of first-line tumour necrosis factor inhibitors in axial spondyloarthritis: results from the EuroSpA Research Collaboration Network
Ronald F van Vollenhoven,
Bente Glintborg,
Merete Lund Hetland,
Ulf Lindström,
Brigitte Michelsen,
Elsa Vieira-Sousa,
Florenzo Iannone,
Eirik Klami Kristianslund,
Dan Nordström,
Karel Pavelka,
Ziga Rotar,
Maria Jose Santos,
Catalin Codreanu,
Gary J Macfarlane,
Mikkel Østergaard,
Michael T Nurmohamed,
Jiri Vencovsky,
Rosario Foti,
Bjorn Gudbjornsson,
Matija Tomšič,
Lykke Midtbøll Ørnbjerg,
Adrian Ciurea,
Árni Jón Geirsson,
Irene van der Horst-Bruinsma,
Michael S Nissen,
Ovidiu Rotariu,
Isabel Castrejón,
Johan K Wallman,
Marleen van de Sande,
Anne G Loft,
Pasoon Hellamand,
Thomas Klausch,
Anna Mari Hokkanen,
Corina Mogosan,
Lucia Otero-Varela,
Semih Gulle,
Berrin Zengin
Affiliations
Ronald F van Vollenhoven
Amsterdam Rheumatology and Immunology Center (ARC), Reade and Amsterdam UMC, Amsterdam, The Netherlands
Bente Glintborg
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Merete Lund Hetland
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Ulf Lindström
Department of Rheumatology and Inflammation Research, University of Gothenburg Sahlgrenska Academy, Goteborg, Sweden
Brigitte Michelsen
Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway
Elsa Vieira-Sousa
Serviço de Reumatologia e Doenças Ósseas Metabólicas, Centro Hospitalar Universitário Lisboa Norte EPE, Lisboa, Portugal
Florenzo Iannone
Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J) Policlinic Hospital, University of Bari, Bari, Italy
Eirik Klami Kristianslund
Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway
Dan Nordström
Departments of Medicine and Rheumatology, Helsinki University Central Hospital, Helsinki, Finland
Karel Pavelka
Department of Rheumatology, Institute of Rheumatology, Prague, Czech Republic
Ziga Rotar
Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia
Maria Jose Santos
Department of Rheumatology, Hospital Garcia de Orta EPE, Almada, Portugal
Catalin Codreanu
Center for Rheumatic Diseases, University of Medicine and Pharmacy, Bucuresti, Romania
Gary J Macfarlane
Aberdeen Centre for Arthritis and Musculoskeletal Health (Epidemiology Group), University of Aberdeen, Aberdeen, UK
Mikkel Østergaard
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Michael T Nurmohamed
Amsterdam Rheumatology and Immunology Center, Amsterdam, Noord-Holland, The Netherlands
Jiri Vencovsky
Department of Rheumatology, Institute of Rheumatology, Prague, Czech Republic
Rosario Foti
Division of Reumathology, A.O.U. Policlinico-San Marco, Catania, Italy
Bjorn Gudbjornsson
Centre for Rheumatology Research, Landspitali University Hospital, Reykjavik, Iceland
Matija Tomšič
Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia
Lykke Midtbøll Ørnbjerg
Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark
Adrian Ciurea
Department of Rheumatology, Zurich University Hospital, University of Zurich, Zurich, Switzerland
Árni Jón Geirsson
Department of Rheumatology, University Hospitali, Reykjavik, Iceland
Irene van der Horst-Bruinsma
Department of Rheumatology, Radboudumc, Nijmegen, Netherlands
Michael S Nissen
Department of Rheumatology, Geneva University Hospitals, Geneve, Switzerland
Ovidiu Rotariu
Aberdeen Centre for Arthritis and Musculoskeletal Health (Epidemiology Group), University of Aberdeen, Aberdeen, UK
Isabel Castrejón
Department of Rheumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
Johan K Wallman
Department of Clinical Sciences Lund, Rheumatology, Skåne University Hospital, Lund University, Lund, Sweden
Marleen van de Sande
Department of Rheumatology and Clinical Immunology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
Anne G Loft
Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark
Pasoon Hellamand
Department of Rheumatology and Clinical Immunology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
Thomas Klausch
Department of Epidemiology and Data Science, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands
Anna Mari Hokkanen
Department of Medicine, Helsinki University and Helsinki University Hospital, Helsinki, Finland
Corina Mogosan
Center for Rheumatic Diseases, University of Medicine and Pharmacy, Bucuresti, Romania
Lucia Otero-Varela
Research Unit, Spanish Society of Rheumatology, Madrid, Spain
Semih Gulle
Division of Rheumatology, Department of Internal Medicine, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey
Berrin Zengin
Division of Rheumatology, Department of Internal Medicine, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey
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.