Infliximab, sold under brand names like Remicade, Inflectra, and Avsola, is a powerful biologic medication prescribed for a range of chronic inflammatory conditions. Its purpose is to modulate the immune system by targeting and neutralizing tumor necrosis factor-alpha (TNF-α), a protein that plays a central role in promoting inflammation throughout the body. For patients whose bodies produce an excessive amount of TNF-α, this therapy can reduce inflammation, alleviate symptoms, and prevent further tissue damage.
What is infliximab?
Infliximab is a type of monoclonal antibody, a protein engineered in a lab to mimic the body's natural antibodies. Specifically, it's a chimeric antibody, meaning it's partly human and partly mouse. This design allows it to be more effective and less likely to trigger a severe immune response in humans compared to fully murine antibodies. Its primary target is TNF-α, which is a signaling protein (cytokine) that helps regulate immune cells and inflammation. When infliximab binds to both the soluble and membrane-bound forms of TNF-α, it blocks its ability to signal other cells to initiate or continue the inflammatory process. Infliximab was first approved by the FDA in 1998, and since then, several biosimilar products have become available, offering similar safety and efficacy profiles.
Comprehensive list of infliximab uses
Infliximab is FDA-approved for the treatment of several debilitating autoimmune diseases. Its specific uses and dosing regimens vary depending on the condition and patient response.
Inflammatory bowel diseases (IBD)
- Crohn's Disease (adult and pediatric): Infliximab is used for treating moderately to severely active Crohn's disease in adults and children aged 6 and older who have not responded well to conventional therapies. It helps to induce and maintain clinical remission and promote healing of the intestinal lining. It is also effective for managing fistulizing Crohn's disease.
- Ulcerative Colitis (UC) (adult and pediatric): For adults and children aged 6 and older with moderately to severely active UC, infliximab can be used to reduce signs and symptoms, induce and maintain clinical remission, and achieve mucosal healing. In severe cases unresponsive to steroids, it may also help patients avoid a colectomy.
Rheumatologic conditions
- Rheumatoid Arthritis (RA) (adult): In combination with methotrexate, infliximab is indicated for adults with moderately to severely active RA. It is proven to reduce symptoms, inhibit the progression of structural joint damage, and improve physical function.
- Ankylosing Spondylitis (AS) (adult): This medication is used to reduce the signs and symptoms of active ankylosing spondylitis in adults. Research has shown it can significantly improve spinal pain and physical function in patients.
- Psoriatic Arthritis (PsA) (adult): Infliximab helps reduce the signs and symptoms of active arthritis, inhibits structural damage, and improves physical function in adults with psoriatic arthritis. It can be used alone or in combination with methotrexate.
Plaque psoriasis
- Chronic Severe Plaque Psoriasis (adult): Infliximab is indicated for adult patients with extensive or disabling plaque psoriasis who are candidates for systemic therapy and have not responded to other treatments. It has demonstrated rapid and significant improvement in skin lesions.
How is infliximab administered?
Infliximab is administered via intravenous (IV) infusion, meaning it is delivered directly into a vein. The process typically takes at least two hours and is performed in a clinical setting under the supervision of a healthcare professional. To minimize potential infusion reactions, patients may be given premedication, such as acetaminophen or antihistamines, beforehand.
The treatment schedule involves an initial induction phase followed by a maintenance phase. For most indications, the standard induction regimen consists of three infusions given at weeks 0, 2, and 6. The maintenance phase usually involves infusions every 6 to 8 weeks thereafter.
Benefits vs. risks: A comparison table
When considering treatment with infliximab, it is crucial to weigh its benefits against its potential risks. A consultation with a healthcare provider is necessary to determine if the treatment is appropriate.
| Aspect | Benefits of Infliximab | Risks of Infliximab |
|---|---|---|
| Efficacy | Often leads to rapid and significant symptom reduction and sustained remission in moderate-to-severe disease. | Response can be lost over time, and some patients do not respond to initial therapy. |
| Disease Progression | Inhibits the progression of structural damage in rheumatoid and psoriatic arthritis. | Potential for severe adverse events, including opportunistic infections and malignancies. |
| Mucosal Healing | Promotes mucosal healing in IBD, which is associated with better long-term outcomes. | Rare but serious side effects like hepatotoxicity and nervous system disorders. |
| Function & Quality of Life | Improves physical function and overall quality of life for patients with chronic, debilitating conditions. | Infusion reactions can occur during or after treatment, though they are often manageable. |
| Drug-free Remission | Can lead to long-term, drug-free remission in some cases, particularly with early intervention. | Requires careful monitoring for potential reactivations (e.g., Hepatitis B, TB). |
Important safety considerations
Infliximab carries a Boxed Warning regarding its most significant risks, which require careful consideration and monitoring by both the patient and the healthcare team.
- Serious Infections: Infliximab suppresses the immune system, increasing the risk of serious and sometimes fatal infections. This includes bacterial, viral, and fungal infections, as well as the reactivation of latent tuberculosis (TB) and Hepatitis B. Before starting therapy, patients are tested for these conditions, and monitoring continues throughout treatment.
- Malignancies: An increased risk of certain cancers, particularly lymphomas, has been observed in patients treated with TNF blockers, including infliximab. This risk may be higher in pediatric and young adult patients, particularly when combined with other immunosuppressants. Periodic skin examinations are also recommended due to an increased risk of skin cancers.
- Cardiovascular and Neurologic Events: Infliximab can worsen heart failure in some patients, and its use is contraindicated in those with moderate to severe heart failure. There have also been reports of rare nervous system disorders, including demyelinating diseases like multiple sclerosis.
- Infusion Reactions: Allergic-type reactions can occur during or shortly after infusion, or as a delayed reaction several days later. Symptoms can include fever, rash, itching, and chest pain.
How infliximab works: The mechanism of action
The central mechanism behind infliximab's therapeutic effect is its interaction with TNF-α. In a healthy immune system, TNF-α is produced to help fight infections and regulate inflammation. However, in autoimmune diseases, an overproduction of TNF-α leads to a chronic inflammatory state that damages healthy tissue.
Infliximab effectively neutralizes this overabundance of TNF-α in several ways:
- Neutralizing Soluble TNF-α: It binds to and blocks the soluble form of the cytokine, preventing it from activating cell surface receptors and triggering inflammatory cascades.
- Binding Membrane-Bound TNF-α: By binding to the form of TNF-α expressed on the surface of immune cells, infliximab induces a process called reverse signaling. This can lead to cell death (apoptosis) of the TNF-α-producing cells, effectively reducing the source of the inflammation.
- Complement Activation: The binding of infliximab to membrane-bound TNF-α can activate the complement system, a part of the immune system that helps clear pathogens and damaged cells.
- Reduced Cell Trafficking: Infliximab decreases the expression of adhesion molecules on endothelial cells, which are critical for recruiting immune cells to sites of inflammation. This helps reduce the buildup of inflammatory cells in affected tissues, such as the gut or joints.
For more detailed scientific information, the National Institutes of Health (NIH) provides articles on infliximab's mechanism of action.
Conclusion
Infliximab is a cornerstone of modern treatment for several chronic inflammatory and autoimmune diseases, offering significant relief and improved quality of life for many patients. By targeting the inflammatory protein TNF-α, it can effectively manage conditions like Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. While its benefits are substantial, it is not without risk, and patients must be carefully selected and monitored throughout therapy. The decision to use infliximab is a complex one, requiring thorough evaluation of a patient's condition, medical history, and risk factors, emphasizing the importance of working closely with a healthcare provider specializing in these conditions.
