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A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality
  1. Charlotte Hyldgaard1,
  2. Ole Hilberg2,
  3. Alma Becic Pedersen3,
  4. Sinna Pilgaard Ulrichsen3,
  5. Anders Løkke1,
  6. Elisabeth Bendstrup1,
  7. Torkell Ellingsen4,5
  1. 1Department of Respiratory Diseases, Aarhus University Hospital, Aarhus, Denmark
  2. 2Department of Medicine, Vejle Hospital, Vejle, Denmark
  3. 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
  4. 4Department of Rheumatology, Odense University Hospital, Odense, Denmark
  5. 5Clinic for Rational and Innovative Patient Pathways, Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark
  1. Correspondence to Dr Charlotte Hyldgaard, Department of Respiratory Diseases, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark; chahyl{at}


Objectives To compare mortality risks in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and patients with RA without ILD.

Design Matched cohort study.

Setting The study was conducted in Denmark, using nationwide, prospectively collected data.

Participants Among patients with RA diagnosed between 2004 and 2016, 679 patients with RA-ILD were matched for birth year, gender and age at RA diagnosis with 11 722 patients with RA but without ILD.

Main outcome measures Mortality risks were assessed using Kaplan-Meier mortality curves, and hazard rate ratios (HRRs) for death were estimated using Cox proportional hazards regression models.

Results The number of prevalent RA patients more than doubled from 15 352 to 35 362 individuals during the study period. RA-ILD was seen in 2.2% of incident RA patients. 34.0% of RA-ILD cases were diagnosed within 1 year prior to and 1 year after the RA diagnosis. One-year mortality was 13.9% (95% CI, 11.4% to 16.7%) in RA-ILD and 3.8% (95% CI, 3.5% to 4.2%) in non-ILD RA, 5-year mortality was 39.0% (34.4% to 43.5%) and 18.2% (17.3% to 19.1%) and 10-year mortality was 60.1% (52.9% to 66.5%) and 34.5% (32.8% to 36.1%), respectively. The HRRs for death were 2 to 10 times increased for RA-ILD compared with non-ILD RA, irrespective of follow-up period. Stratified analysis showed that the HRR for death was highest in the first months after the diagnosis of RA-ILD was made, especially in patients diagnosed with RA before diagnosis of ILD. HRR was higher in males and in patients without comorbidity as assessed by the Charlson Comorbidity Index.

Conclusions ILD is a serious complication in RA, with a significantly increased mortality compared with a large matched cohort of RA comparisons without ILD.

  • Rheumatoid Arthritis
  • Epidemiology
  • Pulmonary Fibrosis

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  • Contributors CH, EB, OH and TE conceived the study idea and developed it in collaboration with ABP, SPU and AL. CH, ABP and SPU collected the data. CH, TE, EB, AL, AB, and OH reviewed the literature. ABP and SPU directed the initial analyses. These were developed further by the other coauthors and then carried out by ABP and SPU. CH, OH, ABP, SPU, AL, EB and TE participated in the discussion and interpretation of the results. CH organised the writing and wrote the initial draft. All authors critically revised the manuscript for intellectual content and approved the final version before submission. CH is the guarantor.

  • Funding The study was supported by a grant from The Danish Rheumatism Association and by the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation.

  • Competing interests None declared.

  • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval The study was approved by the Danish Data Protection Agency (record number 1-16-02-277-16). As this study did not involve contact with patients or an intervention, it was not necessary to obtain permission from the Danish scientific ethical committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.