Infliximab

Approved Uses

Infliximab is used to treat conditions where the immune system attacks healthy parts of the body. It is typically prescribed for patients with moderate to severe symptoms, often when other medications have not been effective enough.

Gastrointestinal Disorders

• Crohn's Disease: Used in adults and children (6 years and older) to reduce symptoms and maintain remission. It is also used to help close and treat draining enterocutaneous and rectovaginal fistulas.
• Ulcerative Colitis: Used in adults and children (6 years and older) to reduce symptoms, induce and maintain clinical remission, and improve the appearance of the intestinal lining.

Joint and Bone Conditions

• Rheumatoid Arthritis: Used in combination with methotrexate to reduce symptoms, improve physical function, and slow the progression of joint damage in adults.
• Ankylosing Spondylitis: Used to reduce signs and symptoms in adults with this inflammatory disease that primarily affects the spine.
• Psoriatic Arthritis: Used to reduce symptoms, improve physical function, and slow the progression of structural damage in adults.

Skin Conditions

• Plaque Psoriasis: Used in adults with chronic severe plaque psoriasis who are candidates for systemic therapy and when other treatments are less appropriate.

Mechanism of Action

Infliximab belongs to a class of medications known as tumor necrosis factor (TNF) blockers. It is a monoclonal antibody, which is a type of protein designed to recognize and bind to a specific target in the body.

The primary target of infliximab is a substance called tumor necrosis factor-alpha (TNF-alpha). In a healthy body, TNF-alpha helps the immune system fight infections. However, in people with certain autoimmune diseases, the body produces too much of this protein. Excessive TNF-alpha leads to chronic inflammation, which can damage healthy tissues and cause symptoms like pain, swelling, and redness.

When infliximab is administered, it attaches itself to TNF-alpha molecules. This action prevents the protein from binding to its receptors on cells, effectively neutralizing its ability to trigger inflammation. By lowering the activity of TNF-alpha, infliximab helps to:

• Reduce inflammation in the joints, skin, and digestive tract.
• Decrease the physical symptoms associated with autoimmune disorders.
• Prevent further damage to tissues and organs.

Common Side Effects

The following side effects are frequently reported and are often mild:

• Headache
• Stomach pain, nausea, or vomiting
• Stuffy or runny nose, sore throat, or sinus pain
• Cough
• Fatigue or tiredness

Serious Side Effects

Contact a healthcare provider immediately if you experience any of the following serious symptoms:

• Signs of infection: Fever, chills, night sweats, or a persistent cough.
• Liver problems: Yellowing of the skin or eyes, dark urine, or pain in the upper right side of the stomach.
• Heart failure symptoms: New or worsening shortness of breath, swelling in the ankles or feet, or sudden weight gain.
• Nervous system issues: Numbness, tingling, vision changes, or weakness in the arms or legs.
• Lupus-like syndrome: Joint pain or a rash on the cheeks or arms that worsens when exposed to the sun.
• Blood disorders: Pale skin, easy bruising, or unusual bleeding.
• Severe allergic reactions: Hives, difficulty breathing, or swelling of the face, lips, or throat.

Infusion Reactions

Some side effects may occur during or shortly after the infusion. Tell your healthcare provider right away if you feel dizzy, nauseated, itchy, or experience chest pain, fever, or chills during the treatment.

Boxed Warnings

Infliximab has boxed warnings for serious infections and malignancy. Because it affects the immune system, it can increase the risk of developing life-threatening infections, including tuberculosis (TB), bacterial sepsis, and invasive fungal infections. Patients must be tested for TB before and during treatment. Treatment should not be initiated if an active infection is present.

There is also an increased risk of lymphoma and other cancers in children and adolescent patients. A rare, often fatal type of cancer called hepatosplenic T-cell lymphoma has occurred in some young adults using infliximab alongside other specific medications for inflammatory bowel disease.

Heart and Liver Complications

This medication may cause new or worsening heart failure. It has also been associated with severe liver damage, which can lead to liver failure or the need for a transplant. Monitoring for signs of jaundice (yellowing of the skin or eyes), extreme fatigue, or swelling is necessary.

Neurological and Blood Disorders

Infliximab may worsen or contribute to the development of demyelinating diseases, such as multiple sclerosis or Guillain-Barre syndrome. Additionally, some patients may experience a significant drop in blood cell counts, which can increase the risk of bleeding or further infection.

Allergic Reactions and Vaccinations

• Infusion Reactions: Serious allergic reactions, including anaphylaxis, can occur during or shortly after the infusion.
• Delayed Hypersensitivity: Some patients may experience fever, rash, or joint pain several days after treatment.
• Vaccines: Live vaccines should not be administered while receiving infliximab, as the drug may reduce the body's ability to respond safely to the vaccine.

Pregnancy

Research on the use of infliximab during pregnancy is limited. While studies have not consistently shown an increased risk of birth defects, the medication is known to cross the placenta, particularly during the third trimester. This exposure may affect the immune system of the newborn.

If you are pregnant or planning to become pregnant, consider the following points for discussion with a clinician:

• Immune System Effects: Infants exposed to infliximab in the womb may have a higher risk of infection after birth.
• Vaccination Schedule: Healthcare providers may recommend delaying live vaccines for infants who were exposed to this medication before birth. This delay often lasts for at least six months after the parent's last dose during pregnancy.
• Clinical Necessity: The medication is typically used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breastfeeding

Infliximab has been detected in human breast milk in very low levels. It is currently unknown if these small amounts cause harm to a nursing infant. Because the long-term effects are not fully established, it is important to consult with a healthcare professional to weigh the benefits of breastfeeding against the potential risks to the infant while receiving treatment.

Administration Forms

Infliximab is supplied in two primary formats for administration:

• Powder for Reconstitution: This is a lyophilized powder provided in vials. It must be mixed with a sterile liquid and further diluted by a healthcare professional before it is administered as an intravenous infusion.
• Solution for Injection: Some versions of this medication are available as a pre-mixed liquid solution. This form is intended for subcutaneous injection, which is delivered into the fatty tissue just under the skin.

The intravenous form is typically administered by a healthcare professional in a clinical setting, while the subcutaneous form may be available in prefilled syringes or autoinjector pens for use after proper training.

FDA Approval and Indications

Infliximab is approved by the U.S. Food and Drug Administration (FDA) for the treatment of several chronic conditions in adults and, in some cases, children. These include:

• Crohn's disease and ulcerative colitis
• Rheumatoid arthritis (used in combination with methotrexate)
• Ankylosing spondylitis
• Psoriatic arthritis
• Chronic severe plaque psoriasis

The FDA has also approved several biosimilar versions of infliximab, which are highly similar to the original reference product.

Boxed Warnings

The FDA requires a boxed warning for infliximab due to the risk of serious side effects:

• Serious Infections: Patients taking infliximab are at increased risk for developing serious infections that may lead to hospitalization or death. These include tuberculosis (TB), bacterial sepsis, and invasive fungal infections.
• Malignancy: Lymphoma and other cancers, some fatal, have been reported in children and adolescent patients treated with TNF blockers like infliximab. A specific type of rare cancer called hepatosplenic T-cell lymphoma has occurred primarily in adolescent and young adult males with inflammatory bowel disease.

Regulatory Requirements

Before starting treatment, the FDA recommends that patients be tested for latent tuberculosis. Healthcare providers must also monitor patients for signs of infection and certain types of skin cancer during treatment.

How the Infusion is Given

Infliximab is delivered slowly through a needle or catheter placed into a vein, a process known as an intravenous (IV) infusion. This procedure must be performed by a healthcare professional who can monitor your response to the medication in a clinical environment.

Duration and Schedule

The infusion typically takes at least two hours to complete. The treatment schedule usually begins with three initial doses given over a six-week period (at weeks 0, 2, and 6). After these starting doses, maintenance infusions are generally administered every six to eight weeks, depending on the specific condition being treated and the patient's response.

Monitoring for Reactions

Because some patients may experience an infusion reaction, healthcare providers will watch you closely during the procedure and for a period of time afterward. Symptoms of a reaction can include:

• Fever or chills
• Chest pain
• Shortness of breath
• High or low blood pressure
• Itching or rash

In some cases, delayed reactions can occur several days after the infusion. It is important to notify your doctor if you experience muscle or joint pain, fever, or swelling of the face and hands within 12 days of receiving a dose.