The findings may ease fears of potentially toxic pulmonary effects in this patient cohort.
Patients with rheumatoid arthritis-associated interstitial lung disease who initiated TNF inhibitor therapy did not have an increased likelihood of respiratory hospitalisation or death, according to a new US study.
Approximately one in 10 patients with rheumatoid arthritis are also affected by interstitial lung disease, which has a poor survival rate. Although disease-modifying antirheumatic drugs (DMARDs) like tumour necrosis factor inhibitors are becoming a more popular treatment option for RA patients, little is known about their safety and effectiveness in patients with associated ILD – leading the American College of Rheumatology to conditionally recommend not using TNF inhibitors as an initial therapy in this cohort.
But a new US retrospective cohort study, published in The Lancet Rheumatology, performed a real-world comparison of initiating TNF inhibitors versus non-TNF inhibitors in patients with RA-associated ILD. They found no differences in the likelihood of death and/or respiratory hospitalisation between the two treatment groups.
“In the absence of trials of DMARDs in RA-associated ILD, these findings provide reassurance and suggest that avoiding TNF inhibitors in patient with RA-associated ILD might be unnecessary,” the authors of an accompanying commentary concluded.
Researchers analysed pharmacy dispensing data and medication administration records held by the US Department of Veterans Affairs to identify RA-associated ILD patients who had initiated a TNF inhibitor or a non-TNF inhibitor therapy, using propensity score matching to reduce the variability between cohorts to match patients in the two treatment groups based on factors such as age, gender, RA and ILD duration and previous treatment history.
The final sample for the primary analysis (a composite outcome of death or respiratory hospitalisation in the first three years after starting treatment) consisted of 237 patients who had initiated TNF inhibitors and 237 patients who had initiated non-TNF inhibitors. The average age of included patients was 68, and 92% of the sample were male.
After adjusting for BMI, erythrocyte sedimentation rate or C-reactive protein elevation and inhaled corticosteroid use, there was no difference in the likelihood of patients receiving TNF inhibitors dying or experiencing a respiratory hospitalisation in the three years after treatment initiation (adjusted HR 1.21, 95% confidence interval 0.92-1.58).
The researchers found no differences between groups in a range of secondary, subgroup and sensitivity analyses, including comparing the likelihood of death and respiratory hospitalisation as separate outcomes rather than a composite, limiting the follow-up period to one year rather than three years or only considering patients who had previously been treated with a DMARD.
“Our results do not suggest that systematic avoidance of TNF inhibitors is required in all patients with RA-associated ILD,” the researchers concluded.
“[But] given disease heterogeneity and [the] imprecision of our estimates, some populations of patients with RA-associated ILD might benefit from specific biological or targeted synthetic DMARD treatment strategies.”
Caution must be taken when interpreting the findings as the majority of patients included in the current study were men – but RA is normally two to three times more common in women.
However, the authors of the accompanying commentary felt the findings raised important questions about RA disease activity and RA-associated ILD outcomes.
“Previous research has shown that RA disease activity represents an important risk factor for the development of ILD. The effect of RA disease activity on the progression of pulmonary inflammation and fibrosis in RA-associated ILD remains unclear, but choosing an effective therapy could plausibly be more important than the specific medication choice,” they wrote.
