OBJECTIVES: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and tumor necrosis factor (TNF) blocking agents have been widely used in the treatment of SpA. Recent evidence has shown anti-TNF therapies may induce hepatic injury. Interleukin inhibitors, a newer drug class with potentially lower side effects, have recently been approved for use. We aim to assess the risk of treatment-related liver injury among patients with SpA utilizing real-world data.

METHODS: A retrospective, claims-based observational study was conducted in a multi-state health system from 2010 to 2017. SpA patients were identified by diagnosis codes and proposed treatment agents, including NSAIDs, anti-TNF agents, and interleukin inhibitors. The primary outcome was 12-month incidence of liver injury after each treatment. Liver injury was evaluated as abnormal liver function test lab values.

RESULTS: The majority of patients (98.9%, n=16,348) received NSAIDs only for first-line treatment. Of those, 1.6% (n=259) changed from NSAIDs to second-line monotherapy treatment with anti-TNF agents (n=249) or interleukin inhibitors (n=6), or polytherapy with at least 2 anti-TNFs ± NSAIDs or anti-TNF + interleukin ± NSAIDs (n=4). Before the second-line treatment, liver injury rate at first-line was 8.5% (22/259),serving as a benchmark. Patients receiving anti-TNF agents as second-line treatment had a similar incidence of liver injury compared to the benchmark (9.2% vs 8.5%, p=0.768). Patients receiving interleukin inhibitors as second-line treatment did not have any liver injuries incidence, however no statistical significance was found due to the small sample size (0% vs 8.5%, p=1.000). Additionally, patients receiving a polytherapy had a higher incidence of liver injury (50.0% vs 8.5%, p=0.043), and the incidence remained high (33.3%) in clinical perspective after excluding those pre-existing liver injuries at first-line.

CONCLUSIONS: Treatment with a polytherapy of TNFs and/or interleukin inhibitors might increase the risk of liver injury. Further studies with larger sample sizes are needed to validate these findings.