Risk of TB Highest Within 6 Months of Starting TNF Inhibitors for RA

SAN FRANCISCO, CA—Patients with rheumatoid arthritis (RA) who initiate TNF inhibitor therapy have an increased risk of tuberculosis, with the highest risk of incidence within the first 6 months, researchers concluded at the 2015 ACR/ARHP Annual Meeting.

Those who were elderly and had received adalimumab and infliximab vs. etanercept were more likely to develop tuberculosis, the study found.

Data from several observational studies have demonstrated the relationship between TNF inhibitor treatment and development of tuberculosis. Clinical guidelines currently recommend screening for latent tuberculosis infection prior to starting TNF inhibitor therapy, as it may lower risk of developing active tuberculosis in patients taking TNF inhibitors.

Yon-Kyoung Sung, MD, from Hanyang University Hospital for Rheumatic Diseases, Clinical Research Center for Rheumatoid Arthritis in Seoul, South Korea, explained, “there is still limited evidence of the risk of tuberculosis in RA patients who used TNF inhibitors after introduction of latent tuberculosis infection screening and treatment guidelines.”

Dr. Sung and colleagues set out to estimate the incidence of tuberculosis in patients who used TNF inhibitors after the introduction of the guidelines, and to evaluate the safety of resuming biologic DMARDs (bDMARDS) in patients who developed tuberculosis post-TNF inhibitor treatment. Using the Korean national healthcare claims database, the authors identified a retrospective cohort of patients with RA (n=4,638) who started treatment with TNF inhibitors between January 2009 and December 2013.

Development of tuberculosis was defined via ICD-10 code plus use of at least 3 of 4 anti-tuberculosis agents: isoniazid, rifampin, ethambutol, and pyrazinamide. Researchers then calculated tuberculosis incidence rate per 100,000 person-years for patients starting TNF inhibitors based on total patients with RA. The team also compared characteristics between the “resuming bDMARD group” vs. “conventional DMARD group” and estimated the rate of tuberculosis relapse among patients who resumed bDMARDs.

Results showed that among patients who started TNF inhibitors as the first bDMARD, 81 patients developed tuberculosis during follow-up. The incidence rate for patients taking TNF inhibitors based on total RA patients was 1.10 per 100,000 person-years (95% CI: 0.86–1.34). Within the first 6 months, the incidence rate was 1.56 (95% CI: 1.02–2.10), which gradually decreased, the authors reported.

Of patients who developed tuberculosis during follow-up, 30 (37%) had resumed use of bDMARDs, with 2 experiencing reactivation of tuberculosis. The mean interval between development of tuberculosis and resuming bDMARDs was 3.3 months. Among these patients, half had changed their bDMARD and half were re-treated with previous bDMARDs.

"When they changed their bDMARDs, 7 patients were switched to etanercept, 4 patients were switched to rituximab, 2 patients to abatacept, 1 patient to adalimumab, and 1 patient to tocilizumab," Dr. Sung reported.

"Therefore, resuming bDMARDs should be undertaken with careful monitoring of tuberculosis relapse,” he concluded.