Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial.

Autor:	Lend K; Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centers, Amsterdam, The Netherlands kristina.lend@ki.se.; Division of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, Sweden., Lampa J; Division of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, Sweden.; Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden., Padyukov L; Division of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, Sweden.; Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden., Hetland ML; Department of Clinical Medicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark.; Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet Glostrup, Glostrup, Denmark., Heiberg MS; Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway., Nordström DC; Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.; University of Helsinki, Helsinki, Uusimaa, Finland., Nurmohamed MT; Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.; Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands., Rudin A; Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden.; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden., Østergaard M; Department of Clinical Medicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark.; Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet Glostrup, Glostrup, Denmark., Haavardsholm EA; Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway., Hørslev-Petersen K; Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark.; Department of Regional Health Research, University of Southern Denmark, Odense, Syddanmark, Denmark., Uhlig T; Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway.; University of Oslo, Oslo, Norway., Sokka-Isler T; Department of Medicine and University of Eastern Finland, Jyväskylä Central Hospital, Jyväskylä, Finland., Gudbjornsson B; Centre for Rheumatology Research, Landspitali University Hospital, Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Grondal G; Centre for Rheumatology Research, Landspitali University Hospital, Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Frazzei G; Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centers, Amsterdam, The Netherlands., Christiaans J; Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centers, Amsterdam, The Netherlands., Wolbink G; Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.; Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands.; Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands., Rispens T; Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.; Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, The Netherlands., Twisk JWR; Department of Epidemiology and Data Science, Amsterdam University Medical Centres, Amsterdam, The Netherlands., van Vollenhoven RF; Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.; Division of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2024 Nov 14; Vol. 83 (12), pp. 1657-1665. Date of Electronic Publication: 2024 Nov 14.
DOI:	10.1136/ard-2024-226024
Abstrakt:	Objectives: To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT). Methods: Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking. Results: In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks. Conclusions: Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice. Trial Registration Number: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815. Competing Interests: Competing interests: LP reports institutional support for the present manuscript from Amsterdam University Medical Centers. MLH reports institutional grants from AbbVie, Bristol Myers Squibb, Eli Lilly, MSD, Pfizer, Sandoz, Novartis, Nordforsk and UCB; speaker honoraria from Medac, Novartis, Pfizer, Sandoz and UCB; institutional data safety monitoring board or advisory board fees from AbbVie. MLH has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data and is partly funded by Novartis and UCB. DCN reports research grant from MSD; consulting fees from Bristol Myers Squibb, Lilly, Novartis, Pfizer, and UCB; speaker honoraria from Pfizer and UCB; participation on a data safety monitoring board or advisory board fees from UCB. MØ reports institutional grants from AbbVie, Amgen, Bristol Myers Squibb, Merck, Celgene, Eli Lilly Novartis and UCB; personal speaker honoraria from AbbVie, Bristol Myers Squibb, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB; participation on a data safety monitoring board or advisory board personal fees from AbbVie, Bristol Myers Squibb, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB. EAH reports institutional grant from research council of Norway; personal speaker honoraria from Pfizer, UCB and Novartis; and participation on a data safety monitoring board or advisory board fees from AbbVie, Pfizer and Eli Lilly. TU reports personal speaker honoraria from Lilly, Pfizer, UCB and Galapagos. TR reports a patent application (TR is the inventor) based on the use of bioengineered IgG targets for the characterisation of rheumatoid factor reactivity patterns. RFvV reports institutional support for the present manuscript from Bristol Myers Squibb; institutional grants for research or education from Alfasigma, AstraZeneca, Bristol Myers Squibb, Galapagos, MSD, Novartis, Pfizer, Roche, Sanofi and UCB; consulting fees from AbbVie, AstraZeneca, Biogen, Bristol Myers Squibb, Galapagos, GSK, Janssen, Pfizer, RemeGen and UCB; speaker honoraria from AbbVie, AstraZeneca, Bristol Myers Squibb, Galapagos, GSK, Janssen, Pfizer and UCB; and participation on a data safety monitoring board or advisory board fees from AbbVie, AstraZeneca, Biogen, Bristol Myers Squibb, Galapagos, GSK, Janssen, Pfizer, RemeGen and UCB. All other authors declare no competing interests. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)
Databáze:	MEDLINE
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