Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoid arthritis: A European retrospective multicohort analysis |
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| Institution: | 1. CESP, INSERM UMR 1018, Faculty of Medicine, Paris-Sud University, Paris-Saclay University, UVSQ, Villejuif, France;2. Amsterdam Rheumatology and Immunology Center, Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands;3. GlaxoSmithKline, Stevenage, UK;4. University of Cambridge, Cambridge, UK;5. Ghent University, Ghent, Belgium;6. Medical Center Slotervaart, Amsterdam, the Netherlands;7. Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands;8. Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden;9. Department of Rheumatology, Lapeyronie Hospital, Montpellier University, Montpellier, France;10. Department of Rheumatology, AP-HP, Pitié Salpétrière Hospital, Paris, France;11. UPMC, GRC 08, Pierre Louis Institute of Epidemiology and Public Health, Paris, France;12. INSERM UMR 996, Faculty of Pharmacy, Paris-Sud University, Paris-Saclay University, Châtenay-Malabry, France;13. Clinical Immunology Laboratory, AP-HP, Paris-Sud University Hospitals, Le Kremlin Bicêtre Hospital, Le Kremlin Bicêtre, France;14. IPSEN, Slough, Berkshire, UK;15. Department of Neurology, Innsbruck Medical University, Innsbruck, Austria;p. GlaxoSmithKline, Uxbridge, Middlesex, UK;q. Sanofi, Chilly-Mazarin, France;r. SciCross AB, Skövde, Sweden;s. Department of Clinical Neuroscience, Clinical Neuroimmunology, Karolinska Institutet, Stockholm, Sweden;t. Unit of Computational Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden;u. UTCBS, CNRS UMR 8258, INSERM U1022, Faculty of Pharmacy, Paris-Descartes-Sorbonne-Cité University, Paris, France;v. AP-HP, Paris-Sud University Hospitals, Paul Brousse Hospital, Villejuif, France;w. CHU Sainte Justine, Quebec, Canada;x. INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Paris-Sud University, Paris-Saclay University, Le Kremlin-Bicêtre, France;y. Department of Rheumatology, AP-HP, Paris-Sud University Hospitals, Le Kremlin Bicêtre Hospital, Le Kremlin-Bicêtre, France;1. Department of Rheumatology - Hôpital Cochin. Assistance Publique - Hôpitaux de Paris, Paris Descartes University, France;2. Gastroenterology Department, Paris Descartes University, Sorbonne Paris Cité, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France;3. Department of Pharmacy, Paris Descartes University, Sorbonne Paris Cité, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France;4. Immunology Laboratory, Paris Descartes University, Sorbonne Paris Cité, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France;5. Internal Medicine Department, Paris Descartes University, Sorbonne Paris Cité, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France;6. INSERM (U1153): Clinical epidemiology and biostatistics, PRES Sorbonne Paris-Cité. Paris, France;1. Service d''Immunologie-hématologie et Rhumatologie pédiatrique, Institut Imagine, Hôpital Necker, Assistance Publique Hôpitaux de Paris, France & Centre National de Référence RAISE, 149 rue de Sèvres, 75015 Paris, France;2. Service d''Immunologie Biologique, Groupe Hospitalier Universitaire Paris-Sud, Hôpital Kremlin Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France;3. INSERM -UMR_S996, Université Paris-Saclay, Clamart, France;4. Service d''Hémato-Onco Pédiatrie, CHRU Nancy, 54511 Vandoeuvre les Nancy, France;5. Service de Néphrologie et Rhumatologie pédiatrique, Hôpital Purpan, Toulouse, France;6. Service de Pédi atrie générale, Hôpital A de Villeneuve, Montpellier, France;7. Service de Pédiatrie générale, Hôpital Mère-Enfants, Nantes, France;8. Service de Pédiatrie générale, Hôpital Robert Debré, Paris, France;9. Université Sorbonne Paris Cité, Paris, France;10. Unité de Recherche Clinique Paris Descartes Necker Cochin, Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Tarnier, Paris, France;11. Université Paris Descartes, Sorbonne Paris Cité, EA 7323, Paris, France;12. Service de Néphrologie, Rhumatologie et Dermatologie pédiatriques, Hôpital Femme-Mère-Enfants, Hospices Civils de Lyon, France & Centre National de Référence RAISE, Bron, France;13. INSERM U1111, Université de Lyon 1, France;14. UTCBS, CNRS UMR 8258, INSERM U1022, Faculté de Pharmacie de Paris, Université Sorbonne-Paris-Cité, Université Paris- Descartes, Paris, France |
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| Abstract: | ObjectivesTo evaluate the incidence of anti-drug antibody (ADA) occurrences and ADA-related risk factors under adalimumab and infliximab treatment in rheumatoid arthritis (RA) patients.MethodsThe study combined retrospective cohorts from the ABIRISK project totaling 366 RA patients treated with adalimumab (n = 240) or infliximab (n = 126), 92.4% of them anti-TNF naive (n = 328/355) and 96.6% of them co-treated with methotrexate (n = 341/353) with up to 18 months follow-up. ADA positivity was measured by enzyme‐linked immunosorbent assay. The cumulative incidence of ADA was estimated, and potential bio-clinical factors were investigated using a Cox regression model on interval-censored data.ResultsADAs were detected within 18 months in 19.2% (n = 46) of the adalimumab-treated patients and 29.4% (n = 37) of the infliximab-treated patients. The cumulative incidence of ADA increased over time. In the adalimumab and infliximab groups, respectively, the incidence was 15.4% (5.2–20.2) and 0% (0–5.9) at 3 months, 17.6% (11.4–26.4) and 0% (0–25.9) at 6 months, 17.7% (12.6–37.5) and 34.1% (11.4–46.3) at 12 months, 50.0% (25.9–87.5) and 37.5% (25.9–77.4) at 15 months and 50.0% (25.9–87.5) and 66.7% (37.7–100) at 18 months. Factors associated with a higher risk of ADA development were: longer disease duration (1–3 vs. < 1 year; adalimumab: HR 3.0, 95% CI 1.0–8.7; infliximab: HR 2.7, 95% CI 1.1–6.8), moderate disease activity (DAS28 3.2–5.1 vs. < 3.2; adalimumab: HR 6.6, 95% CI 1.3–33.7) and lifetime smoking (infliximab: HR 2.7, 95% CI 1.2–6.3).ConclusionsThe current study focusing on patients co-treated with methotrexate for more than 95% of them found a late occurrence of ADAs not previously observed, whereby the risk continued to increase over 18 months. Disease duration, DAS28 and lifetime smoking are clinical predictors of ADA development. |
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