Hospitalization, mortality risks in RA-ILD similar for TNF inhibitors, non-TNF agents
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SAN DIEGO — TNF inhibitors demonstrate comparable risks for hospitalization and death vs. non-TNF agents in patients with rheumatoid arthritis-associated interstitial lung disease, according to data presented at ACR Convergence 2023.
“People with RA-ILD can have a difficult disease course, with a median survival of 4 to 8 years,” Bryant England, MD, PhD, of the Veterans Affairs Nebraska-Western Iowa Health Care System and the University of Nebraska Medical Center, told Healio. “But when it comes to selecting therapies, there is not a lot of good evidence to guide which therapies are most efficacious in which populations.”
England added that there is “some concern in the literature” about whether TNF inhibitors are safe to use in these patients.
“Because we do not have trial-level data, we wanted to simulate a clinical trial using real-world data,” he added.
To compare outcomes among patients with RA-ILD receiving TNF inhibitors vs. non-TNF/Janus kinase inhibitor therapies, England and colleagues conducted an active-comparator analysis of patients seen within the Veterans Health Administration between 2006 and 2018. The primary analysis included 474 patients with RA-ILD, of whom 237 were treated with a TNF inhibitor. These patients were matched to 237 patients who received a non-TNF inhibitor agent or JAK inhibitor.
“We used a propensity score matching approach to make sure the patients in each group were quite similar,” England said.
Patients who used mycophenolate or antifibrotics that could be used specifically to treat ILD were excluded. The cohort had a mean age of 68 years and was 92% men. The primary endpoint was a composite of time to respiratory-related hospitalization or mortality. The researchers also assessed for respiratory hospitalization or all-cause or respiratory mortality. The duration to the primary endpoint was 3 years, with 1-year findings representing the secondary endpoint.
Among the patients who received a TNF inhibitor, 51% used adalimumab (Humira, Abbvie), while 37% were prescribed etanercept (Enbrel, Amgen). The most commonly used non-TNF/JAK treatments were rituximab (Rituxan, Genentech), at 53%, and abatacept (Orencia, Bristol Myers Squibb), at 28%.
According to the researchers, there were no significant differences between TNF inhibition and non-TNF/JAK inhibition regarding the primary endpoint (HR = 1.19; 95% CI, 0.91-1.56; adjusted HR = 95% CI, 1.22; 0.92-1.6). Respiratory hospitalizations, all-cause mortality and respiratory-related mortality also were comparable between the two groups.
“Our [previous] beliefs have been based on lower-quality evidence suggesting worse outcomes in RA-ILD with TNF-inhibitor treatment,” England said. “But in our study, we did not observe that TNF inhibitors resulted in a worse outcome. However, despite our observational approach, we really need clinical trial data to more clearly illustrate whether our advanced RA therapies are efficacious in this high-risk population.”
He added that it also remains to be confirmed whether TNF inhibition can impact RA-ILD.
“While we did not find a difference between TNF inhibition and non-TNF inhibition, this does not mean that TNF inhibitors can treat RA-ILD,” England said. “What it means is that if you received a drug in this class, you did not have a worse mortality or respiratory-related hospitalization rate. It is a subtle but important distinction.”
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England BM. Abstract 1582. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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