Calip GS, et al. - Researchers investigated tumor necrosis factor-alpha inhibitor (TNFI)-related risk of non-Hodgkin lymphoma (NHL) by duration and type of anti-TNF agent used. This is in light of a black box warning issued by the US Food and Drug Administration (FDA) for the use of TNFIs and risk of NHL. This warning for NHL was supported by the findings, and continued surveillance and awareness of this rare but serious adverse outcome are justified, especially with new TNFIs and biosimilar products forthcoming.

Methods

• In this nested case-control study within a retrospective cohort of adults with rheumatologic conditions taken from a US commercial health insurance database between 2009 and 2015, researchers identified use of TNFIs (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol) and conventional-synthetic disease-modifying antirheumatic drugs (csDMARDs).
• They estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL using conditional logistic regression models.

Results

• This analysis included 101 NHL cases and 984 controls matched on age, gender and rheumatologic indication.
• Relative to controls, greater TNFI use was found in NHL cases (33% vs. 20%) but csDMARD use was similar (70% vs 71%).
• TNFI ever-use was found to be related to nearly two-fold increased risk of NHL (OR = 1.93; 95% CI: 1.16–3.20) with an indication of increasing risk with duration (P-trend = 0.05).
• TNF fusion protein (etanercept) was noted to be related to increased NHL risk (OR = 2.73; 95% CI: 1.40–5.33), whereas no statistically significant risk with anti-TNF monoclonal antibodies was found (OR = 1.77; 95% CI: 0.87–3.58).
• Channeling bias was not likely to account for the results, as observed in sensitivity analyses assessing confounding by rheumatologic disease severity.