Incidence of seropositive and seronegative rheumatoid arthritis in Denmark: a nationwide population-based study

Abstract

Objective

To investigate and compare trends in incidence rates (IRs) of seropositive and seronegative rheumatoid arthritis (RA) in Denmark using various data sources for serostatus definition.

Method

This nationwide population-based cohort study was based on data from Danish healthcare and clinical quality registries between 2000 and 2018. Information on anti-cyclic citrullinated peptide and immunoglobulin M rheumatoid factor was obtained, and definitions of seropositivity according to the number of applied data sources were prespecified. Annual age- and sex-standardized IRs were calculated as the number of incident seropositive and seronegative cases, divided by the number of person-years (PY) in the general population in that given year.

Results

An increasing temporal trend in IR of seropositive RA and a decreasing trend in seronegative RA were observed. The IRs were higher for seropositive RA than for seronegative RA from 2009 onwards, with a widening of the IR gap between 2009 and 2016 regardless of the definition of seropositivity. When combining laboratory- and physician-reported autoantibody information and ICD-10 codes, the IR of seropositive RA in 2018 was approximately twice that of seronegative RA, at 19.0 and 9.0 per 100 000 PY, respectively. The level of antibody testing increased significantly during the study period.

Conclusions

The IR of seropositive RA increased over time, whereas the IR of seronegative RA decreased. Temporal IR changes may be caused by a real change in the RA serology subtypes, an increase in autoantibody testing and availability, changes in registration practice over time, or a combination of these factors.

Disclosure statement

Bolette G Soussi reports grants from the Danish Rheumatism Association and the Frimodt-Heineke Foundation during the conduct of this study; grants from Grosserer LF Foghts Foundation, the North Denmark Region, Aalborg University Hospital, EULAR congress bursary, and ACR congress bursary outside the present work; and Novo Nordisk stocks. René L Cordtz is employed by IQVIA outside the present work. Kirsten Duch reports grants from the Danish Rheumatism Association and the North Denmark Region outside the present work. Salome Kristensen has nothing to disclose. Daniel Prieto-Alhambra’s department has received grant(s) from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma; his research group has received consultancy fees from AstraZeneca and UCB Biopharma; and Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organized by DPA’s department. Asta Linauskas has nothing to disclose. Christian S Bork reports a grant from the Karen Elise Jensens Foundation outside the present work. Erik B Schmidt has nothing to disclose. Lene Dreyer reports a contract with BMS outside the present work, and support for attending conferences from Janssen, UCB, and Boehringer Ingelheim; and is chair of the scientific committee of the Danish Rheumatism Association, a member of DANBIO’s steering committee, and a member of ethical scientific committee 3 in Denmark.

Authors’ contributions

RL Cordtz, L Dreyer, and BG Soussi conceptualized the study with respect to devising appropriate study design and statistical methods. K Duch, RL Cordtz, and BG Soussi had direct access to the underlying data and take full responsibility for the integrity of the data, as well as statistical analyses. All authors were involved in the critical appraisal and interpretation of data. BG Soussi drafted the first manuscript and finished the manuscript after critical revision from the co-authors. All authors approved the final version of the manuscript and take responsibility for the decision to submit it for publication.

Data availability statement

Enquiries about data sharing will be handled in accordance with the data-handling laws from the European General Data Protection Regulation (GDPR). The Danish Data Protection Agency and Statistics Denmark prohibit extraction and sharing of any data making individuals identifiable.

Ethics statement

The study has been approved by the Data Protection Committee of Northern Jutland, Denmark (2021-084). No ethical approval was required by Danish law.

Patient and public involvement

No patient research partner was involved in the design, conduct, or reporting of this study.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/03009742.2024.2365540

Additional information

Funding

This work was supported by the Danish Rheumatism Association and the Frimodt-Heineke Foundation. The study was sponsored by Aalborg University Hospital, Denmark. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.