RA Treatment with Tocilizumab Linked to Liver Enzyme Abnormalities

Elevations in liver enzymes were common in patients treated with intravenous tocilizumab, but serious hepatic adverse events were rare, according to a recent study.

In their study, researchers analyzed pooled data from clinical trials that included 4171 patients treated with intravenous tocilizumab at doses of 4, 8, or 10 mg/kg with or without disease-modifying antirheumatic drugs (DMARDs). The researchers assessed alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which were measured routinely in all trials, and calculated rates of hepatic adverse events per 100 patient-years of tocilizumab exposure.
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Overall, 16,204.8 patient-years of tocilizumab exposure were evaluated.

ALT elevations above the upper limit of normal (ULN) occurred in 70.6% of patients, and elevations of AST above ULN occurred in 59.4% of patients. Most elevations occurred during the first year of treatment, with 59% and 55% of patients experiencing ALT and AST elevations 1 to 3 times above ULN, respectively, 8.9% and 3.3% of patients experiencing elevations 3 to 5 times above ULN, respectively, and 2.9% and 0.9% of patients experiencing elevations 5 times above ULN, respectively.

Single ALT and AST elevations that were 3 times above ULN occurred in 7.7% of patients and 3.6% of patients, respectively, and 2 or more consecutive elevations of ALT and AST that were 3 times above ULN occurred in 1.9% and 0.4% of patients, respectively. The majority of those who experienced elevations 3 times above ULN (80%) returned to normal over a median of 5.6 weeks. ALT and AST elevations were the reason for the withdrawal from treatment for 2.5% of patients.

Seven serious hepatic adverse events occurred in the studies, with a rate of 0.04 per 100 patient-years.

“Transaminase elevations with tocilizumab were frequent, but rates of hepatic SAEs were low in this clinical trial data set,” the researchers concluded. “Regular monitoring, with dose adjustment of tocilizumab/DMARDs for persistent elevations, is recommended.”

—Melissa Weiss

Reference:

Genovese MC, Kremer JM, van Vollenhoven RF, et al. Transaminase Levels and Hepatic Events During Tocilizumab Treatment: Pooled Analysis of Long-Term Clinical Trial Safety Data in Rheumatoid Arthritis [published online August 1, 2017]. Arthritis & Rheumatology. doi:10.1002/art.40176.