Infliximab, Biologics: Infusion Precautions
By Marianna Herrera, RN, BSN, IgCN - November 11, 2022

Biologics products have been developed to treat undesirable immune responses caused by chronic systemic inflammatory conditions. The immune system consists of a vast network of cells, tissues and organs that all perform specific functions to help keep the "host" in a state of equilibrium. Infliximab is a monoclonal antibody tumor necrosis factor α (TNF) inhibitor. That has been used to slow the progression of several inflammatory conditions, such as rheumatoid arthritis by blocking the activation of TNF, target specific therapy.

What is TNF? TNF is a cytokine (activator) that has many contradictory functions. Typically, TNF is detected in inflammatory, infectious conditions and after tissue injury. It induces the inflammatory cascade and is then followed by interleukin (IL)-6 and IL-1. In an event of an acute infection or tissue injury TNF is detected in serum almost immediately and up to 2 and 48 hours after. In instances of keeping the host in a state of equilibrium this is a very useful process. However, there has been continuous detection of TNF in patients with immune dysregulation. TNF has functions for degeneration and cell repair, cellular proliferation and apoptosis and in anti-tumor and tumor pro-growth properties. When TNF is activated in response to acute situations it is very beneficial to the host, but when it is constantly active and activating the inflammatory response, it can have undesirable effects for the host. Elevated concentrations of TNFα have been found in the tissues and fluids of patients with conditions such as rheumatoid arthritis, ulcerative colitis, Crohn's disease and ankylosing spondylitis.

Although many patients have benefited from using infliximab, it is imperative that we understand the effects this biologic can have on the body and what needs to be looked at with more care and what education a patient needs to be provided with when receiving infliximab.

Infliximab Therapy Side Effects - [Download PDF]

Contraindications:

• Patients with moderate to severe heart failure. During clinical trials evaluating TNF blockage as a treatment for heart failure have shown worsening disease progression in patients with NYHA class III-IV congestive heart failure (CHF). TNF activates apoptosis in compromised heart cells, therefore, by blocking TNF, compromised cells are not "destroyed "and patients with heart conditions may worsen. Patients with CHF could receive Infliximab, but the prescriber must evaluate the risk vs benefit of treating the patient with Infliximab and they must not receive doses greater than 5mg/kg.
• Monitor patients and educate patients on the following symptoms: shortness of breath with activity or while laying down, fatigue and weakness, swelling of legs/ankles/feet, sudden weight gain from fluid retention and chest pain.
• Stop infliximab therapy if new or worsening heart failure occurs.
• Patients who have hypersensitivity to infliximab, inactive ingredients, murine proteins or if they have experienced a severe hypersensitivity reaction to infliximab. Infliximab is a chimeric mAb, which means approximately 75% of the DNA sequence is human, however, the DNA sequence in the variable domain within the antigen binding fragment (Fab) remains murine.

Warnings and Precautions:

• Anaphylaxis can occur at any time during first and/or subsequent infusions. Always have anaphylaxis kit readily available.

• Serious infections (box warning) Patients treated with infliximab are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients are taking concomitant immunosuppressants such as methotrexate or corticosteroids, that deplete their immune system in a broader form. Other infections such as tuberculosis (TB), invasive fungal (including histoplasmosis, coccidioidomycosis, candidiasis and aspergillosis) and bacterial infections, viral or other infections caused by opportunistic pathogens have been reported. TNF is crucial for the clearance of intracellular pathogens, it also helps form and maintain granulomas in TB and induces apoptosis of TB infected cells.
• Infliximab should not be initiated in patients with an active infection, including clinically important localized infections.
• Patients at higher risk of infection include age greater than 65 years, co-morbid conditions and/or those taking concomitant immunosuppressants.
• Monitor and educate patients on following symptoms: severe cough lasting 3 weeks or longer, chest pain, coughing up blood or sputum, weakness or fatigue, unexplained weight loss, loss of appetite, chills, fever, night sweats.

Malignancies:

• Malignancies, especially lymphoma is a known risk of immunosuppression. During the trial period of infliximab, lymphoma and other malignancies have been reported in children and adolescents treated with TNFα inhibitors. In further studies it was determined most of the patients that developed malignancies were receiving concomitant immunosuppressant treatment. TNF has a tumor-promoting potential under certain conditions.

Hepatitis B virus (HBV) reactivation:

• May result in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation and monitor patients during and after treatment. If reactivation occurs, stop infliximab therapy and begin antiviral therapy. This can occur due to the inactivation on TNF function of differentiation and phagosome formation.

Hepatotoxicity:

• Elevated liver function tests have been observed in patients receiving infliximab.
• Monitor and educate patients on following symptoms: right-sided abdominal pain, dark urine, fever, nausea and vomiting, weakness and fatigue, rash and yellowing of skin or whites of eyes.

Blood dyscrasias, including neutropenia, anemia, thrombocytopenia:

• Monitor and educate patients on following symptoms: signs of infection, shortness of breath, pallor and bruising easily or bleeding.

Demyelinating Disorders:

• The role of TNF in demyelinating disorders is still under investigation.
• Rarely, new or worsening of neurological conditions such as demyelinating disease, multiple sclerosis, and Guillain-Barre syndrome.

SLE and Lupus-like syndrome:

• Infliximab may cause formation of autoantibodies and rarely, the development of lupus-like syndrome. Infliximab should be discontinued if this occurs.
• Increased cell lysis in patients treated with infliximab may lead to exposure to self-antigens.
• Monitor and educate patients on following symptoms: Severe allergic reaction, including difficulty breathing, shortness of breath and swelling around the eyelids, lips and cheeks.

TNF has many important functions that activate different events in the immune system. Due to its contradictory functions TNF is extremely helpful in maintaining homeostasis, but in constant and large amounts it could be detrimental to one's health. Luckily, advances have found a way to specifically block TNF and slow down progression and responses of the immune system with biologic products such as infliximab.