Infliximab

Infliximab belongs to the class of biological response modifiers called tumour necrosis factor (TNF) blockers. It is currently approved for the treatment of rheumatoid arthritis and Crohn disease. However, recent clinical trials of infliximab for the treatment of psoriasis and psoriatic arthritis are proving it to be an effective treatment for these conditions. In one major study, infliximab very quickly and effectively controlled the psoriasis and in about half the patients stopped the disease progressing further after just 3 doses of the medicine.

Experimentally, infliximab has been shown to help some patients with other serious inflammatory skin conditions such as hidradenitis suppurativa, pyoderma gangrenosum and pemphigus vulgaris.

How does it work?

Infliximab is biologically engineered from human and mouse antibody molecules. It works by directly binding to TNF molecules in the blood and diseased tissue. Infliximab-bound TNF cannot bind to or activate TNF receptors, which is the primary cause of the inflammation, redness, itching and flaky skin patches characteristic of psoriasis.

How is it given?

For the treatment of psoriasis and psoriatic arthritis, infliximab is administered by intravenous infusion under specialist supervision. Only a doctor experienced in its use should use it, and emergency treatment must be available in case of acute infusion-related reactions. Patients receiving infliximab require close supervision and monitoring throughout treatment.

Infliximab is usually given in combination with methotrexate, which helps to prevent the formation of anti-infliximab antibodies. It is administered by intravenous infusion over 2 hours and repeated after 2 and 6 weeks.

Contraindications

Infliximab should not be used under the following circumstances:

• untreated chronic infection, such as tuberculosis or hepatitis B/C
• patients with moderate to severe congestive heart failure
• known hypersensitivity to murine proteins or any other component of the product.

Precautions

Because infliximab works by selectively targeting only those chemicals involved in causing psoriasis, theoretically it should not have an effect on the rest of the body's immune system. Even so caution must be taken when considering its use in patients prone to infections or in those with chronic or recurrent infections.

• Patients should be tested for tuberculosis (TB) before starting infliximab.
• Treatment should be stopped if serious infection occurs, for example requiring hospitalisation or intravenous antibiotics. It can often be recommenced once the infection has been effectively treated.
• Uncommon infections with organisms such as listeria and legionella may be more common and more serious in patients on infliximab.

Infliximab should also be used with caution in the following situations:

• mild congestive heart failure
• pre-existing central nervous system (CNS) disorders, e.g. seizures
• elderly patients
• patients with kidney or liver failure
• pregnancy and breastfeeding

Side effects

Infliximab appears to be well tolerated. If any of the following symptoms are severe or do not go away you should contact your doctor.

• Coughing
• Nausea and/or vomiting
• Stomach pain
• Headache
• Fever and night sweats
• Fatigue and muscle weakness
• Unexpected weight loss

Acute infusion-related reactions include difficulty in breathing or swallowing, chest pain, swelling of face, lips, or hands, dizziness and headache, flushing, urticaria, and burning at the IV infusion site. These may be treated by reducing the rate of infusion, and with paracetamol and antihistamines.

In a small number of patients, lupus-like symptoms and signs may occur. These include photosensitivity and joint and muscle pain (arthritis and arthralgias). Treatment should be stopped if these occur.

Severe cutaneous reactions have rarely been reported, including Stevens Johnson syndrome and toxic epidermal necrolysis.

Like all medications that work on the immune system, it may increase the risk of certain types of lymphoma (white blood cell cancer). These have rarely been reported in patients on infliximab, usually in those also taking other medicines that suppress the immune system such as azathioprine or mercaptopurine. Skin cancers, in particular squamous cell carcinoma, have also been reported usually in patients on infliximab. These patients usually have other risk factors such as previous treatment with photochemotherapy (PUVA).