The incidence and prevalence of extra-articular and systemic manifestations in a cohort of newly-diagnosed patients with rheumatoid arthritis between 1999 and 2006

Curr Med Res Opin. 2008 Feb;24(2):469-80. doi: 10.1185/030079908x261177.


Objective: To evaluate the incidence and prevalence of extra-articular (ExRA) and systemic (SysM) manifestations in a cohort of newly-diagnosed patients with rheumatoid arthritis (RA) in the United States.

Patients and methods: Retrospective analysis using inpatient, outpatient, and pharmacy claims data contained in the Thomson Healthcare MarketScan research databases. Patients >or= 18 years of age with a diagnosis of RA (ICD-9-CM 714.0x) on three non-diagnostic claims on different days between January 1, 1999 and September 30, 2006, and at least 12 months of continuous enrollment prior to, and at least 2 years following diagnosis were included in the analysis. Thirty ExRA/SysM, classified into six groups (cardiovascular, blood, mucosa, pulmonary, other, and non-specific), were evaluated. Patients were followed until in-hospital death, disenrollment, or study end.

Results: A total of 16,752 patients were included (mean age 59.8 +/- 13.5 years; 72.0% female), and were followed up for a mean of 3.9 +/- 1.4 years. ExRA/SysM were experienced by 47.5% of patients, with cardiovascular (27.2%) the most common. The most frequent individual ExRA/SysM was 'other CVD' (17.2%). Female sex was associated with a reduced risk of cardiovascular ExRA/SysM (HR, 0.66; 95% CI, 0.61-0.72), and an increase in mucosa ExRA/SysM (HR, 2.55; 95% CI, 2.03-3.19). Prior treatment with methotrexate (MTX) was associated with significantly reduced risks of cardiovascular (HR 0.65; 95% CI, 0.59-0.72) and blood system (HR 0.71; 95% CI, 0.61-0.82) ExRA/SysM. Other significant associations were also evident: age, comorbidity as measured by CCI and CDS, and geographic region were associated with increased risks for some ExRA/SysM, while prior NSAID treatment and the presence of diabetes were associated with a lower risk for some ExRA/SysM.

Conclusion: ExRA/SysM develop in approximately 47% of patients with RA within a few years of diagnosis. Prior treatment with some therapies used in RA management were associated with a reduced risk of developing some ExRA/SysM, while several demographic factors and the presence of comorbidities also affected the risk of developing ExRA/SysM. This analysis was restricted to patients with employer- or government-funded health insurance, while several potential predictors of ExRA/SysM could not be controlled for in the multivariate analysis, as they could not be measured using claims data. Hence, these results may not be generalizable to other groups of patients with RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia / epidemiology
  • Anemia / etiology*
  • Anti-Inflammatory Agents, Non-Steroidal
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / epidemiology
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology*
  • Comorbidity
  • Female
  • Humans
  • Incidence
  • Male
  • Methotrexate
  • Middle Aged
  • Prevalence
  • Retrospective Studies
  • Risk Factors
  • United States / epidemiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Methotrexate