Opin vísindi

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

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


Title: 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
Author: Stockfelt, Marit
Lundell, Anna Carin
Hetland, Merete Lund   orcid.org/0000-0003-4229-6818
Østergaard, Mikkel
Uhlig, Till
Heiberg, Marte Schrumpf
Haavardsholm, Espen A.
Nurmohamed, Michael T.
Lampa, Jon
Nordström, Dan
... 9 more authors Show all authors
Date: 2021-07-13
Language: English
Scope: 189
Department: Faculty of Medicine
Internal Medicine and Emergency Services
Series: Arthritis Research and Therapy; 23(1)
ISSN: 1478-6354
DOI: https://doi.org/10.1186/s13075-021-02556-1
Subject: Sjúkdómsgreining; Iktsýki; Lyfjameðferð; Antirheumatic Agents; Arthritis, Rheumatoid; Drug therapy; Diagnosis; Autoantibodies; Humans; Antirheumatic Agents/therapeutic use; Anti-Citrullinated Protein Antibodies; Rheumatoid Factor; Interferon-alpha/therapeutic use; Arthritis, Rheumatoid/diagnosis; Rheumatology; Immunology and Allergy; Immunology
URI: https://hdl.handle.net/20.500.11815/3076

Show full item record

Citation:

Stockfelt , M , Lundell , A C , Hetland , M L , Østergaard , M , Uhlig , T , Heiberg , M S , Haavardsholm , E A , Nurmohamed , M T , Lampa , J , Nordström , D , Petersen , K H , Guðbjörnsson , B , Gröndal , G , Aldridge , J , Andersson , K , Blennow , K , Zetterberg , H , van Vollenhoven , R & Rudin , A 2021 , ' 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 ' , Arthritis Research and Therapy , vol. 23 , no. 1 , 189 , pp. 189 . https://doi.org/10.1186/s13075-021-02556-1

Abstract:

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.

Description:

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. Publisher Copyright: © 2021, The Author(s).

Files in this item

This item appears in the following Collection(s)