Long-term elevated inflammation raises ILD risk in rheumatoid arthritis
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Key takeaways:
- Persistently elevated ESR and CRP in patients with RA were associated with greater risk for interstitial lung disease.
- Control of systemic inflammation may aid in prevention of RA-ILD.
Patients with rheumatoid arthritis who demonstrate consistent long-term elevation of inflammatory markers have an increased risk for interstitial lung disease, according to data published in Arthritis Research & Therapy.
“Several studies have identified elevated or moderate disease activity as a contributing factor for RA-ILD,” Ronja Ramien, of the German Rheumatology Research Center, in Berlin, and colleagues wrote. “Of note, most of the studies only used values from one single time point, eg, study enrolment or ILD onset. In terms of systemic inflammation, results are inconclusive.
“To date, only one study has methodically focused on disease activity as a risk factor for incident ILD in RA patients,” they added. “They also focused on the inflammatory marker CRP, but did not include ESR.”
To determine how the development of ILD in RA correlates with disease activity, particularly via erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, Ramien and colleagues conducted a nested case-control study using the RABBIT register, a German cohort of patients with RA. The study included 139 patients with RA and incident ILD, matched with 686 controls with RA but no ILD. The mean observation time across the whole cohort was 38 months.
The researchers used conditional logistic regression models to analyze the effects of ESR and CRP, assessed using subscales of DAS28, on the incidence of ILD. According to the researchres, both values were log-transformed in regression analyses due to skewed distribution. A directed acyclic graph was drawn to identify covariates to be adjusted for, including rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis or chronic viral infections.
According to the researchers, mean DAS28 composite scores, based on either ESR or CRP, had no association with development of ILD in RA. However, increased RA-ILD risk was significantly associated with log ESR alone (OR = 1.86; 95% CI, 1.35-2.57) and log CRP alone (OR = 1.55; 95% CI, 1.21-1.97).
Greater RA-ILD risk was especially associated with continually high inflammation markers prior to ILD. Those with ESR higher than 21 mm/h the entire time were at greater risk than those below (OR = 2.98; 95% CI, 1.72-5.17), and those with CRP consistently above 5 mg/L had greater risk (OR = 3.7; 95% CI, 1.95-6.89) than those who stayed below.
“Systemic inflammation plays a central role in the development of ILD in patients with RA,” Ramien and colleagues wrote. “We found that persistently elevated ESR and CRP levels were associated with a higher chance of developing ILD. Therefore, rheumatologists should not only monitor composite disease activity scores, such as DAS28, but also pay attention to the time-varying levels of ESR and CRP. Tight control of systemic inflammation may thus not only improve the outcome of RA itself, but also help prevent development of RA-ILD. Furthermore, standardized, routine ILD screening is crucial for the early detection of RA-ILD.”
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