Infliximab: an infused TNF blocker for arthritis and bowel disease

The UK product information (Remicade) describes infliximab as a chimeric human-murine monoclonal antibody that binds with high affinity to both soluble and transmembrane TNF-alpha. Blocking TNF reduces the inflammatory signalling that drives conditions such as rheumatoid arthritis and inflammatory bowel disease.

It is given by infusion into a vein, in a clinical setting, which differs from adalimumab and etanercept, which are self-injected under the skin. Biosimilar infliximab products exist and are used under the same safety principles.

In rheumatoid arthritis, infliximab is given in combination with methotrexate to reduce signs and symptoms and improve physical function in adults with active disease when the response to DMARDs has been inadequate, or in severe, active and progressive disease not previously treated with methotrexate; a reduction in X-ray joint damage progression has been demonstrated.

In Crohn disease it is indicated for moderately to severely active disease in adults who have not responded to a full course of a corticosteroid and/or an immunosuppressant, or who cannot take them, and for fistulising Crohn disease after conventional treatment. For children and adolescents aged 6 to 17, it is indicated for severe active Crohn disease not responding to conventional therapy. It is also indicated for moderately to severely active ulcerative colitis after an inadequate response to conventional therapy.

Infliximab has been associated with acute infusion-related reactions, including anaphylactic shock, which can develop within seconds or within a few hours after an infusion, and with delayed hypersensitivity reactions. If an acute reaction occurs, the infusion is interrupted. Antibodies to infliximab may develop and have been associated with a greater frequency of infusion reactions.

Delayed hypersensitivity is more likely with longer gaps between treatments. Concomitant methotrexate or other immunomodulators appear to reduce antibody formation, which is one reason they are often continued alongside it.

Patients must be monitored closely for infections, including tuberculosis, before, during and after treatment, and because elimination may take up to six months, monitoring continues for that period. TNF is essential for clearing intracellular infections, so blocking it makes people more susceptible to serious infections including tuberculosis, bacterial infections such as sepsis and pneumonia, and invasive fungal, viral and other opportunistic infections. Suppression of TNF may mask symptoms of infection such as fever, so early recognition is important.

It is contraindicated in tuberculosis and other severe infections such as sepsis, abscesses and opportunistic infections, in moderate or severe heart failure (NYHA III/IV), and in hypersensitivity to infliximab, other murine proteins or any excipient.

Upper respiratory tract infection was the most common reaction in clinical trials, and viral infections such as influenza and herpes infections are very common. Bacterial infections such as cellulitis and abscess are common, while tuberculosis and fungal infections are uncommon, and meningitis and opportunistic infections are rare.

Rare but important effects include lymphoma, severe liver reactions and blood count problems. Seek advice promptly for fever, a persistent cough, painful skin infections, chest pain, breathlessness, or a rash or swelling soon after an infusion.

Combining infliximab with other biologics for the same conditions, such as anakinra and abatacept, is not recommended. Corticosteroids do not appear to affect infliximab pharmacokinetics to a clinically relevant extent. Live vaccines should not be given concurrently, and live vaccines are not recommended for infants for 12 months after in utero exposure, or for a breastfed infant while the mother is receiving infliximab unless infant serum levels are undetectable.

The product information describes a moderate number of prospectively collected pregnancies without an increase in malformation rate, but infliximab crosses the placenta and can be detected in infants for up to 12 months, with a possible increased risk of infection. It should only be used in pregnancy if clearly needed. Low levels are detected in breast milk, and your specialist will advise on feeding.