LIVERPOOL -- Patients with rheumatoid arthritis who have interstitial lung disease (ILD) appeared to have a survival advantage if treated with rituximab rather than with a tumor necrosis factor (TNF) inhibitor, a researcher said here.
Among patients with usual interstitial pneumonia -- the most severe form of ILD -- death from any cause occurred in 31% of patients treated with anti-TNF therapy compared with 8% of those receiving rituximab (P=0.03), according to Clive Kelly, MBBS, of Queen Elizabeth Hospital in Gateshead, England.
Action Points
- Note that this observational cohort study documented improved mortality among rheumatoid arthritis patients with interstitial lung disease receiving rituximab compared with anti-TNF therapies.
- Be aware that this was not a controlled trial, so patients who received rituximab may have been healthier in general than those who received anti-TNF agents.
"And for respiratory mortality, there was almost a four-fold reduction with rituximab (4% versus 15%, P=0.04)," he reported here at the annual meeting of the British Society for Rheumatology.
It has been known for 50 years that ILD is a prominent feature of rheumatoid arthritis, and pulmonary complications have ranked only behind cardiovascular causes as a major cause of death.
On post-mortem examinations, 40% to 50% of patients with rheumatoid arthritis have had histopathologic evidence of fibrosis, and on high-resolution scans taken during the 1990s, 25% had radiological evidence of fibrosis.
Clinically, 5% of patients have evidence of lung involvement, and textbooks traditionally have estimated that when ILD develops, life expectancy falls to just 3 years.
Recently there have been reports of patients with rheumatoid arthritis-associated ILD treated with biologic therapies having disease progression and accelerated respiratory failure. Some reports have suggested that etanercept (Enbrel) might be safer, but then a case study of 12 patients given etanercept showed that all developed accelerated disease.
To more fully examine the effects of biologic therapy on ILD in rheumatoid arthritis, Kelly and colleagues analyzed data from the British Rheumatoid Arthritis Interstitial Lung Network, which enrolled cases from 16 centers across the U.K. during a 25-year period.
A total of 188 patients in the network have had ILD confirmed with high resolution CT scans between 2000 and 2012 -- the biologic era -- and a similar group of case controls had rheumatoid arthritis but without lung involvement.
Of those 188 with ILD, a total of 57 had been treated with a biological agent. Their mean age at the time of ILD diagnosis was 64, and the male-to-female ratio was 1:1, which is typical for ILD in rheumatoid arthritis.
Mean duration of arthritis was 9 years at the time the lung disease was diagnosed, and mean ILD duration at the time of biologic therapy was 4 years.
In 65% of the patients, the diagnosis was usual interstitial pneumonia.
"There was no real difference in all-cause or respiratory mortality for those with ILD treated with biologics and those treated with other agents, so biologics in general do not appear to be influencing the excess mortality in rheumatoid arthritis ILD," Kelly said.
But when they looked at anti-TNF treatment compared with rituximab, they found statistically significant differences even though the numbers were small, at 30 and 27 patients in the two groups, respectively.
"We therefore propose that a prospective trial be done comparing anti-TNF therapy with rituximab, using hard endpoints, to clarify the legitimacy of preferring B-cell therapy in rheumatoid arthritis ILD," he concluded.
Disclosures
The authors disclosed no relevant relationships with industry.
Primary Source
British Society for Rheumatology
Source Reference: Palmer E, et al "Rheumatoid arthritis-related interstitial lung disease: Association between biologic therapy and survival" BSR 2014; Abstract O36.