Infliximab for Immune Checkpoint Inhibitor Therapy-Related Toxicities

Key Messages

What Is the Issue?

• Immune checkpoint inhibitor (ICI) therapy has become a treatment option for various types of advanced cancer, resulting in significant improvement in disease outcomes.
• However, ICIs can overstimulate the immune system leading to various side effects known as immune-related adverse events (irAEs) that can occur in any organ system.
• Administration of corticosteroids is the initial mainstay treatment of irAEs. However, there is little evidence of how to treat steroid-resistant irAEs. Treatment of steroid-resistant irAEs includes holding ICI and starting immunosuppressive therapy.
• Decision-makers are interested in understanding the use of infliximab, a selective immunosuppressive drug, for the treatment of steroid-resistant irAEs affecting various organs.

What Did We Do?

• We identified and summarized the literature regarding the efficacy and safety of infliximab for the treatment of steroid-resistant irAEs. Due to the limitation of evidence, we included studies of any design, including case reports and case series.
• A research information specialist conducted a literature search of peer-reviewed and grey literature sources published between January 1, 2019 and April 8, 2024. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.

What Did We Find?

• The evidence presented in this report was based on 2 systematic reviews of case reports and case series, 1 retrospective cohort study, and 40 additional publications consisting of 29 case reports and 11 case series.
• We identified 4 main irAEs, which were colitis, hepatitis, pneumonitis, and myocarditis.
• Very low-quality evidence, which was mainly derived from case reports and case series, suggests that infliximab may be effective for the treatment of steroid-resistant immune-induced colitis, while there are concerns regarding its use for the treatment of hepatitis due to potential hepatotoxicity and infectious complications. There is mixed evidence regarding the use of infliximab for the treatment of immune-induced pneumonitis and myocarditis.
• Recent consensus guidelines recommend the use of infliximab as first-line treatment for steroid-resistant immune-induced colitis, while its use for hepatitis is not recommended due to potential hepatotoxicity and infectious complications. The use of infliximab for the treatment of pneumonitis is an option, while its use for myocarditis remains to be determined.
• The usual dose of infliximab was 5 mg/kg, administered by IV. A higher dose of 10 mg/kg was seen in some cases. The number of infusions, the period between infusions and the length of treatment varied depending on the responsiveness of infliximab and the type and severity of irAEs.
• Treatment with infliximab as compared with vedolizumab resulted in comparable immune-induced colitis response rates, higher recurrent rate of colitis, and more hospitalizations despite a shorter time to clinical response.

What Does This Mean?

• The very low-quality evidence identified suggests the potential benefits of infliximab in the management of immune-induced colitis due to its efficacy and fast response.
• When using the clinical evidence and recommendations summarized in this report to inform decisions, decision-makers should consider that the evidence is of very low quality, mainly derived from case reports and case series.
• Large prospective and comparative studies are needed to verify the findings and to determine the role of infliximab in the treatment of other irAEs.