Clinical Information

Drug and target:

Infliximab (IFX) is a chimeric monoclonal antibody (IgG1 kappa) which targets tumor necrosis factor (TNF)-alpha. IFX works by preventing TNF-alpha from binding its cellular receptors through competitive inhibition. IFX recognizes both soluble TNF-alpha trimers circulating in plasma and transmembrane TNF-alpha on cell surfaces.(1) IFX also exhibits anti-inflammatory properties by downregulating several cytokines while enhancing interleukin 10 production.(2,3) The reference product for IFX is Remicade (Janssen Pharmaceuticals).(4) Several biosimilars are US Food and Drug Administration (FDA)-approved, including but not limited to: Renflexis (infliximab-abda, Organon), Inflectra (infliximab-dyyb, Pfizer Inc), Ixifi (infliximab-qbtx, Pfizer Inc), and Avsola (infliximab-axxq, Amgen). Biosimilars have the same primary amino acid sequence as Remicade. Therefore, "infliximab" will be used to refer to the reference product and the biosimilar products interchangeably. This test cannot distinguish between the reference product Remicade and the infliximab biosimilar products.

Indications:

As of December 2025, infliximab is FDA-approved for Crohn disease (adult and pediatric), ulcerative colitis (adult and pediatric), rheumatoid arthritis (in combination with methotrexate), ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.(5) Doses vary by indication, and follow a main framework of intravenous (IV) infusions of induction at weeks 0, 2 and 6, followed by scheduled maintenance IV infusions every 8 weeks thereafter. For Crohn disease and ulcerative colitis, the initial dosing regimen is 5 mg/kg IV over at least 2 hours. For rheumatoid arthritis, the dosing starts at 3 mg/kg IV. There is a newer subcutaneous formulation of IFX, not entirely interchangeable with IV IFX. Its availability depends on the geographic location and indication. In the United States, it is approved for maintenance stages of Crohn disease and ulcerative colitis.

Pharmacokinetic highlights:

Infliximab has a volume of distribution of 3-6 liters and clearance rates of 11-15 mL/hr with a half-life of 14 days. Steady-state concentrations in the body are achieved by week 14.(5,6) IFX clearance is affected by disease state, concomitant use of immunosuppressants, high concentrations of TNF-alpha and C-reactive protein, low albumin concentrations, high body mass index, and presence of anti-drug-antibodies.(7-9) Male patients seem to clear IFX faster than female patients.(9)

Immunogenicity:

Patients may develop anti-drug antibodies-to-infliximab (ATI).(5,10-12) Concomitant use of immunomodulators can reduce the formation of ATI in some patients.(5) ATI formation may increase drug clearance in treated patients or neutralize the drug effect, thereby potentially contributing to the loss of response. ATI could also cause adverse events such as serum sickness and hypersensitivity reactions. Infliximab drug level quantitation is commonly performed in conjunction with immunogenicity assessment for ATI.

Evidence for therapeutic drug monitoring:

Therapeutic drug monitoring (TDM) of IFX is supported by evidence for both reactive and proactive strategies, with stronger consensus for reactive use. Reactive TDM is performed in the setting of loss of response or infusion reactions. Reactive TDM is well validated to distinguish pharmacokinetic failure (low drug, absent antibodies) from immunogenicity (anti-drug antibodies), enabling rational dose escalation or switching and improving cost-effectiveness.(13-15) Proactive TDM studies, involving routine measurement during maintenance stages of therapy, suggests benefits in reducing immunogenicity, maintaining remission, and optimizing long-term exposure, particularly early in therapy and in high-risk patients.(16)

Measurement of IFX concentration is indicated at trough, immediately prior to the next scheduled infusion.(5,6) IFX concentrations tend to reach steady state and stabilize after 14 weeks (approximately 100 days).(17) Quantitation of peak IFX concentration is strongly discouraged.