Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis—a spin-off study of the NORD-STAR randomized clinical trial
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Background: The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods: Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. Results: IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. Conclusion: IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 189 |
| Tidsskrift | Arthritis Research and Therapy |
| Vol/bind | 23 |
| Antal sider | 11 |
| ISSN | 1478-6354 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
AR is supported by the Swedish Research Council (#2019-01035); the Swedish state under the agreement between the Swedish government and the country councils, the ALF-agreement (#ALFGBG-717541); and King Gustaf V’s 80-year foundation (#FAI-2019-0603). MS is supported by the Gothenburg Society of Medicine (#GLS-935039). DN is supported by The Academy of Finland, Finska Läkaresällskapet, and Institutional grant of Helsinki University Hospital. KB is supported by the Swedish Research Council (#2017-00915); the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615); the Swedish Alzheimer Foundation (#AF-742881); Hjärnfonden, Sweden (#FO2017-0243); the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986); the European Union Joint Program for Neurodegenerative Disorders (#JPND2019-466-236); and the National Institute of Health (NIH), USA (grant #1R01AG068398-01). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532); the European Research Council (#681712); Swedish State Support for Clinical Research (#ALFGBG-720931); the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862); the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C); the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228); and the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE) and the UK Dementia Research Institute at UCL. Open access funding is provided by the Gothenburg University library.
Funding Information:
MS, ACL, TU, MTN, JL, KHP, GG, JA, KA, and AR have no competing interests to declare. MLH has received research grants from Abbvie, Biogen, BMS, Celltrion, Eli-Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Bioepis, Sandoz, and Novartis; chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies; and 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. MØ has received research grants from Abbvie, BMS, Merck, Celgene, and Novartis, and speaker and/or consulting fees from Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB. MSH has received speaker’s honoraria from Lilly and Roche over the last 4 years outside the submitted work. EAH has received grants from the Norwegian Regional Health Authorities and The South-Eastern Norway Regional Health Authority during the conduct of the NORD-STAR study, and speaker and/or consulting fees from Pfizer, AbbVie, Celgene, Novartis, Janssen, Gilead, Eli-Lilly, and UCB outside the submitted work. DN has received consulting fees from AbbVie, BMS, MSD, Novartis, Pfizer, Roche, and UCB. BG has received speaking fees from Amgen and Novartis. KB has served as a consultant, at advisory boards or at data monitoring committees for Abcam, Axon, Biogen and JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside the submitted work). HZ has served at scientific advisory boards for Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, and CogRx; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, and Biogen; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). RV has received research and educational support (grants) from BMS, GSK, Lilly, Pfizer, Roche, and UCB and consultancy and/or speaking fees from AbbVie, AstraZeneca, Biogen, Biotest, BMS, Galapagos, Gilead, GSK, Janssen, Pfizer, Sanofi, Servier, UCB, and Vielabio.
Publisher Copyright:
© 2021, The Author(s).
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