Comorbidity in incident rheumatoid arthritis: a nationwide case-control study with bidirectional follow-up

Abstract

Objectives: To investigate the association between risk of different concurrent disorders and diagnosis of rheumatoid arthritis (RA) using a temporal approach.

Methods: Retrospective, case-control study. Data were extracted from all available healthcare claims for Poland between 2011-2021. Prevalent RA (n = 262 265) patients were examined to evaluate morbidity patterns. Incident RA (n = 15 879) and age-, sex- and region-matched controls were sampled 1:10 from the general population (GP). Exposure was new-onset RA identified by interspaced, repeat claims and prescription. Follow-up was performed in a bidirectional, five-year timeframe from RA diagnosis (Dx).

Results: RA is associated with enhanced risk of multiple concomitant disorders both pre- and post-Dx, especially hematologic (incidence rate ratio (IRR) 1.80, 95% CI 1.58, 2.05), pulmonary (IRR 1.57, 95% CI 1.53, 1.62), gastrointestinal (IRR 1.53, 95% CI 1.46, 1.60) and cardiovascular (IRR 1.25, 95% CI 1.22, 1.27) conditions. RA appears strongly associated with interstitial lung disease (pre-Dx IRR 2.97, 95% CI 2.20, 4.02; post-Dx IRR 4.66, 95% CI 3.91, 5.56) and inflammatory bowel disease (pre-Dx IRR 1.61, 95% CI 1.25, 2.07; post-Dx IRR 2.12, 95% CI 1.70, 2.63). Enhanced post-Dx risk of thyroid cancer (IRR 1.29, 95% CI 1.00, 1.66) and lymphoma (IRR 1.50, 95% CI 1.20, 1.88) was observed, in contrast to reduced risk of colon cancer (IRR 0.77, 95% CI 0.62, 0.94).

Conclusion: Enhanced risk of multiple concurrent disorders was observed both pre- and post-RA Dx, with varying patterns across different disease groups. These data highlight the multisystemic nature of RA and warrant further research into causal, bidirectional relationships.

Keywords: cardiovascular; comorbidity; epidemiologic; morbidity; neoplasm; rheumatoid arthritis; risk factor.

Figure 1.

Temporal trends in healthcare utilization for specific disease groups among incident rheumatoid arthritis patients. Disease groups are differentiated based on ICD-10 classification. PR: prevalence rate

Figure 2.

Relative risk of cardiovascular disorders in rheumatoid arthritis patients before and after diagnosis as compared with the general population. Pre- and post- refer to the patients’ status respective to rheumatoid arthritis diagnosis or presumptive diagnosis in case of controls (necessary to establish a bidirectional timeframe of follow-up). Ary: arrhythmia; Cereb: cerebrovascular disease; CAD: coronary artery disease; HF: heart failure; HTN: hypertension; IRR: incidence rate ratio; MI: myocardial infarction; RA: rheumatoid arthritis; VHD: valvular heart disease

Figure 3.

Relative risk of neoplastic disorders in rheumatoid arthritis patients before and after diagnosis as compared with general population. Pre- and post- refer to the patients’ status respective to rheumatoid arthritis diagnosis or presumptive diagnosis in the case of controls (necessary to establish a bidirectional timeframe of follow-up). IRR: incidence rate ratio; NMSC: non-melanoma skin cancer; orig: origin

Figure 4.

Relative risk of selected autoimmune disorders in rheumatoid arthritis patients before and after diagnosis as compared with general population. Pre- and post- refer to the patients’ status respective to rheumatoid arthritis diagnosis or presumptive diagnosis in the case of controls (necessary to establish a bidirectional timeframe of follow-up). IRR: incidence rate ratio; IBD: inflammatory bowel disease; Sarc: Sarcoidosis; Hypothyr: hypothyroidism; MS: multiple sclerosis; IDDM: insulin dependent diabetes mellitus