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Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration
  1. Ulf Lindström1,
  2. Daniela Di Giuseppe2,
  3. Bénédicte Delcoigne2,
  4. Bente Glintborg3,4,
  5. Burkhard Möller5,
  6. Adrian Ciurea6,
  7. Manuel Pombo-Suarez7,
  8. Carlos Sanchez-Piedra8,
  9. Kari Eklund9,10,
  10. Heikki Relas9,
  11. Bjorn Gudbjornsson11,12,
  12. Thorvardur Jon Love12,13,
  13. Gareth T Jones14,
  14. Catalin Codreanu15,
  15. Ruxandra Ionescu16,
  16. Lucie Nekvindova17,18,
  17. Jakub Závada19,20,
  18. Nuh Atas21,
  19. Servet Yolbas22,
  20. Karen Minde Fagerli23,
  21. Brigitte Michelsen23,24,
  22. Žiga Rotar25,26,
  23. Matija Tomšič25,26,
  24. Florenzo Iannone27,
  25. Maria Jose Santos28,
  26. Pedro Avila-Ribeiro29,30,
  27. Lykke Midtbøll Ørnbjerg31,
  28. Mikkel Østergaard31,32,
  29. Lennart TH Jacobsson1,
  30. Johan Askling2,
  31. Michael J Nissen33
  1. 1Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  2. 2Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  3. 3DANBIO and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Copenhagen, Denmark
  4. 4Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  5. 5Department for Rheumatology and Immunology, Inselspital University Hospital Bern, Bern, Switzerland
  6. 6Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
  7. 7Rheumatology Service, Hospital Clinico Universitario, Santiago de Compostela, Spain
  8. 8Research Unit, Spanish Society of Rheumatology, Madrid, Spain
  9. 9Inflammation Center, Department of Rheumatology, Helsinki University Hospital, Helsinki, Finland
  10. 10Orton Orthopaedic Hospital, Helsinki, Finland
  11. 11Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland
  12. 12Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  13. 13Department for Science and Research, Landspitali University Hospital, Reykjavik, Iceland
  14. 14Epidemiology Group, Aberdeen Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Aberdeen, UK
  15. 15Romanian Registry of Rheumatic Diseases, University of Medicine and Pharmacy, Bucharest, Romania
  16. 16Romanian Registry of Rheumatic Diseases, University of Medicine and Pharmacy ”Carol Davila”, Bucharest, Romania
  17. 17First Faculty of Medicine, Charles University, Prague, Czech Republic
  18. 18Institute of Biostatistics and Analyses, Ltd, Brno, Czech Republic
  19. 19Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
  20. 20Institute of Rheumatology, Prague, Czech Republic
  21. 21Division of Rheumatology, Department of Internal Medicine, University Hospital and Faculty of Medicine, Gazi University, Ankara, Turkey
  22. 22Division of Rheumatology, Department of Internal Medicine, University Hospital and Faculty of Medicine, Inonu University, Malatya, Turkey
  23. 23Department of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway
  24. 24Division of Rheumatology, Department of Medicine, Sorlandet Hospital, Kristiansand, Norway
  25. 25Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia
  26. 26Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
  27. 27Rheumatology Unit—DETO, University of Bari, Bari, Italy
  28. 28Reuma.pt registry and Department of Rheumatology, Hospital Garcia de Orta, Almada, Portugal
  29. 29Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
  30. 30Rheumatology Department, Hospital de Santa Maria, Lisboa, Portugal
  31. 31Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet Glostrup, Glostrup, Denmark
  32. 32Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
  33. 33Department of Rheumatology, Geneva University Hospital, Geneva, Switzerland
  1. Correspondence to Dr Ulf Lindström, Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; ulf.lindstrom{at}gu.se

Abstract

Background Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy.

Methods Patients with PsA from 13 European countries who initiated a first TNFi in 2006–2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed.

Results In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12–1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23–1.72)) and infliximab (OR 1.55 (1.21–1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept.

Conclusion This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.

  • arthritis
  • psoriatic
  • tumour necrosis factor inhibitors
  • methotrexate

Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

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Footnotes

  • UL and DDG are joint first authors.

  • Handling editor Josef S Smolen

  • Twitter @hteraG_senoJ

  • Contributors All coauthors have contributed significantly in accordance with contributorship guidelines.

  • Funding This work was supported by Novartis. Novartis had no influence on the data collection, statistical analyses, manuscript preparation or decision to submit. The work was also supported by NordForsk.

  • Competing interests BeG reports grants from BMS, grants from Pfizer, grants from AbbVie, outside the submitted work. AC reports consultancy and speaker fees from Abbvie, Eli Lilly, Merck Sharp & Dohme, Novartis and Pfizer. MP-S reports speaker and research fees from Gilead, Janssen, MSD and Sanofi. KE reports consulting fees from Lilly, Biogene, Sobi, Pfizer and Gilead. HR reports personal fees from AbbVie, personal fees from Roche, personal fees from Pfizer, outside the submitted work. BjG reports other from Novartis, other from Amgen, outside the submitted work. GTJ reports grants from AbbVie, grants from Pfizer, grants from UCB, grants from Celgene / Amgen, grants from GSK, outside the submitted work. CC reports speaker fees and grants from AbbVie, Amgen, Egis, Novartis, Pfizer and UCB. RI reports speaker fee from Abbvie, Amgen, Novartis, Pfizer, Lilly and UCB. JZ reports speaker and consulting fees from Elli-Lilly, Abbvie, Novartis and UCB. SY reports speaker fees from Abbvie, MSD, Novartis, UCB, Sanofi and Pfizer. BM reports grants and personal fees from Novartis, outside the submitted work. ZR reports speaker fees, consultancy fees and support to biorx.si registry by, AbbVie, Amgen, Biogen, Eli Lilly, Janssen, Medias, Medis, MSD, Novartis, OPH Oktal Pharma, Sandoz and Pfizer. MTreports speaker fees, consultancy fees and support to biorx.si registry by, AbbVie, Amgen, Biogen, Eli Lilly, Janssen, Medias, Medis, MSD, Novartis, OPH Oktal Pharma, Sandoz and Pfizer. FI reports consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Lilly, Novartis, Sanofi, Celgene and UCB, outside this work. MJS reports personal fees from Abbvie, Novartis and Pfizer, outside the submitted work. PA-R reports research grant (paid to academic research institute) from Novartis. LMØ reports grants from Novartis, during the conduct of the study. MØ reports grants, personal fees and non-financial support from AbbVie, grants, personal fees and non-financial support from BMS, personal fees from Boehringer-Ingelheim, personal fees from Eli Lilly, personal fees and non-financial support from Janssen, grants, personal fees and non-financial support from Merck, personal fees and non-financial support from Pfizer, personal fees and non-financial support from Roche, grants, personal fees and non-financial support from UCB, grants and personal fees from Celgene, personal fees from Sanofi, personal fees from Regeneron, grants, personal fees and non-financial support from Novartis, personal fees from Gilead, outside the submitted work. LJ reports lecture and consulting fees from Pfizer, Abbvie, Novartis, Eli-Lily and Janssen. JA reports grants from Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, outside the submitted work. MN reports research and consulting fees from Abbvie, Celgene, Eli-Lilly, Janssen, Novartis and Pfizer.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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