Comorbidities Increase in Importance in RA Save

Patients with rheumatoid arthritis (RA) have a large comorbidity burden at the time of diagnosis, including a wide range of ailments but with pulmonary disease a particular concern, a U.K. population-based study found.

Compared with controls, RA patients had a significantly higher rate of chronic lung disease, depression, diabetes, stroke, hemiplegia, and liver disease, according to Karim Raza, BMBCh, PhD, of the University of Birmingham in England, and colleagues.

And for those with chronic obstructive pulmonary disease (COPD), there was an almost threefold increase in mortality risk (HR 2.84, 95% CI 1.13-7.12, P=0.027), the researchers reported in Rheumatology.

The long-term prognosis has improved greatly in RA with the wide use of disease-modifying antirheumatic drugs and biologics as well as a treat-to-target approach to management. But mortality remains higher than in the general population, particularly from causes such as respiratory and cardiovascular diseases and cancer.

"With increasing life expectancy and improved control of joint disease in RA, the relative importance of comorbidity in RA is increasing," the researchers observed.

To examine and quantify the specific comorbidities and their contribution to mortality, they analyzed data from the Royal College of General Practitioners Research and Surveillance Center database, which includes a representative sample of the U.K. primary care population (approximately 1.5 million individuals).

They identified 6,591 patients diagnosed with RA before January 2017, matching them with an equivalent number of non-RA controls. Participants' mean age was 60, and two-thirds were women.

Among the specific comorbidities that were significantly more common in RA patients were the following:

• COPD: 7.1% vs 3.9%, P<0.001
• Asthma: 17% vs 13.5%, P<0.001
• Interstitial lung disease: 0.8% vs 0%, P<0.001
• Depression: 28.1% vs 23%, P<0.001
• Diabetes: 10% vs 8.2%, P<0.001
• Mild liver disease: 2.1% vs 1.4%, P=0.003

There were further increases in comorbidities during the 3 years after RA diagnosis, including hypertension, heart failure, and peptic ulcer disease, and the incidence of COPD, interstitial lung disease, and depression continued to rise.

The mean score on the Rheumatic Disease Comorbidity Index (RDCI) was 1.63 among RA patients compared with 1.38 for controls (P<0.001), while on the Charlson Comorbidity Index, mean scores were 1.68 and 0.55, respectively (P<0.001).

Higher comorbidity scores were associated with a greater risk of all-cause mortality, with adjusted hazard ratios of 1.26 (95% CI 1-1.59, P=0.049) on the RDCI and 1.30 (95% CI 0.99-1.70, P=0.057) for Charlson scores during a mean of 6 years of follow-up.

Among the chronic lung diseases, only COPD showed a significant association with mortality. There was no association between mortality and asthma (HR 1.79, 95% CI 0.75-4.30, P=0.192), and the numbers of patients with interstitial lung disease were too small to evaluate the risk. Among patients whose COPD was present at the time of RA diagnosis, the lung disease preceded RA by a median of 4.5 years, while asthma preceded RA by 12.5 years. Almost half of the patients with interstitial lung disease had the pulmonary diagnosis within 2 years before the RA diagnosis.

The temporal associations between lung diseases and RA have not previously been investigated in a community-based population. The differences, particularly between COPD and asthma, are likely to reflect the disparity in typical age of onset of those diseases, according to the authors.

The greater burden of pulmonary and cardiovascular disease observed among RA patients in this study also may reflect the influence of smoking, with only 29.6% of RA patients never having smoked compared with 35.5% of controls. Moreover, many studies have identified smoking as a risk factor for RA. "This underscores the importance of smoking cessation advice and support as part of the routine management of people with and at risk of RA," Raza and colleagues stated.

The finding that the number of comorbidities continued to increase in the years after RA diagnosis suggested "a need for clinicians to reassess comorbidity frequently post-diagnosis in the RA population, especially as medications used for RA treatment are associated with several comorbidities," they wrote.

"Management of comorbidities, especially preventable and modifiable ones and associated risk factors early on in the disease course may improve outcomes and quality of life," they concluded.

A limitation of the study was the possibility of residual confounding.

The study was funded by Pfizer UK.

The authors reported financial relationships with Pfizer, Sanofi, Gilead, Celltrion, AbbVie, Eli Lilly, Bristol-Myers Squibb, UCB, Janssen, Roche Chugai, and Celgene. Several are employees of Pfizer.