Abstract
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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Annals of the Rheumatic Diseases |
| Vol/bind | 83 |
| Udgave nummer | 12 |
| Sider (fra-til) | 1657-1665 |
| Antal sider | 9 |
| ISSN | 0003-4967 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:We express our gratitude to the patients, study nurses, investigators, joint assessors, data management and study teams who were involved in the NORD-STAR trial. The NORD-STAR trial was funded through the following public sources: the Academy of Finland (grant number 258536); Finska L\u00E4kares\u00E4llskapet; a grant from the South-Eastern Health Regional Health Authority, Norway; a Helsinki University Central Hospital (HUCH) institutional grant, Finland (grant number 1159005); the Icelandic Society for Rheumatology; an inter-regional grant from all health regions in Norway; NordForsk (grant number 70945); Regionernes Medicinpulje, Denmark (grant number 14/217); Stockholm County Council, Sweden (grant number 20100490); the Swedish Medical Research Council (grant numbers C0634901, D0342301, 2015-00891_5); the Swedish Rheumatism Association; and The Research Fund of University Hospital, Reykjavik, Iceland (A2015017). UCB provided certolizumab pegol at no cost. Bristol Myers Squibb provided abatacept at no cost. Additionally, the Karolinska Institute received several unrestricted grants from Bristol Myers Squibb; these were subsequently transferred to the principal investigators of Denmark, Finland and the Netherlands to help defray various trial related costs at the local level. Part of this work has been presented at the EULAR - Annual European Congress of Rheumatology 2024 in Vienna.
Funding Information:
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. M\u00D8 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.
Publisher Copyright:
© 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.