A biologic is a type of drug therapy produced from living cells that are made to target specific parts of the immune system. Anti-TNF agents are now common biologic agents used to treat children and teens with IBD. These drugs are made from proteins that recognize and bind to specific proteins that are responsible for creating inflammation. Using anti-TNF agents help prevent the attack of healthy cells in the GI tract and control IBD causing inflammation.
Though anti-TNF agents are very effective treatments, they can stop working in some patients, even if they were helpful in the beginning. This is known as ‘secondary loss of response.’ This occurs after the body produces antibodies against the drug, which is called ‘sensitization’. Once you have been sensitized to the drug, it no longer works well, and your body becomes ‘resistant’ to the medication. Doctors can help decrease sensitization by monitoring anti-TNF drug levels and combining an anti-TNF agent with an immunomodulator drug (a drug that helps regulate the immune system). We aim to increase ‘durability of response’ or length of time on an effective drug with these measures.
When an anti-TNF agent is taken alone, with no immunomodulator, we call this “mono-therapy.”
And when an anti-TNF agent is combined with an immunomodulator, we call this “combo-therapy”.
There is a strategy behind using combo therapy.
‘Sensitization’ of a biologic agent is thought to occur when the drug level in the body is low. It is thought that if the drug level is zero or close to zero when another dose of medication is given, the body will recognize the drug as foreign and mount an antibody response causing sensitization. Combination therapy is thought to work in different ways. How a drug interacts with your body is unique to each person and can be affected by many factors.
Immunomodulators reduce the body’s immune response to make antibodies. Meaning even if the drug level drops before your next dose, an immunomodulator can reduce the possibility of forming antibodies. Immunomodulators also reduce inflammation in the body by using a different pathway than biologic agents. By reducing inflammation, the biologic therapy is not used up as quickly, which helps keep drug levels up and reduces antibody formation.
For patients who have been on a biologic agent previously, this can be a factor that has shown to be most highly associated with ‘immunogenicity’ or likelihood of developing antibodies. For this reason, we often use combination therapy if it is your second biologic agent. The choice of a biologic agent is also a factor in deciding whether to combine with an immunomodulor.
Different biologic agents have been shown to have differences in rates of sensitizations, even as first-line agents. Among anti-TNFs, some are thought to have lower immunogenicity and are therefore used more often in monotherapy.
When combination therapy is used, it is often dosed at a level patients tolerate well and with few side effects. It is important to let your doctor know if you experience any side effects as there are strategies to reduce symptoms.
Patients may also struggle with taking additional medication. Still, rates of sensitization are highest at the beginning of therapy, and combination drug use may only be for a number of months.
Treatment of IBD, including selecting mono or combo therapy, is best personalized to each individual patient, depending on your disease location, disease activity, treatment history and personal preferences. Communicating with your doctor is the best way to determine a personalized treatment plan that best targets your IBD.
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Dr. Cynthia Popalis contributed to the content and review of this article for accuracy and balance. We thank Dr. Popalis for her time and contribution to our magazine. Dr Cynthia Popalis MD, FRCPC, is a Paediatric Gastroenterologist at Boomerang Health, SickKids’ clinic and Markham, Stouffville Hospital in Markham, Ontario.