What are the considerations for switching to a different tumor necrosis factor (TNF) inhibitor within the same class in patients with inflammatory bowel disease (IBD)?

From the Guidelines

Switching anti-TNF medications within the same class is a reasonable strategy for inflammatory bowel disease (IBD) patients who have lost response to their initial anti-TNF therapy, as supported by the British Society of Gastroenterology consensus guidelines 1. When a patient fails one anti-TNF agent due to loss of response or adverse effects, switching to another medication in the same class (such as from infliximab to adalimumab, certolizumab pegol, or golimumab) can be effective in approximately 40-50% of cases. The decision to switch within class versus switching to a different class of biologics can be guided by therapeutic drug monitoring, which can help determine if the failure is due to antibody formation or inadequate drug levels 1. Some key points to consider when switching anti-TNF medications within the same class include:

• Discontinuing the current anti-TNF agent and initiating the new one at standard induction dosing
• Monitoring patients closely after switching for clinical response, typically within 8-12 weeks of initiating the new therapy
• Considering the use of therapeutic drug monitoring to guide the decision to switch within class versus switching to a different class of biologics
• Being aware of the potential for immune-mediated pharmacokinetic failure, which may require a switch to a different class of biologics 1. It's also important to note that the presence of low drug levels in the presence of high titre antibodies mandates a switch, ideally within class to an alternative anti-TNF therapy, particularly if the patient has previously shown themselves to be anti-TNF responsive 1. Overall, switching anti-TNF medications within the same class can be a effective strategy for managing IBD patients who have lost response to their initial anti-TNF therapy, and should be considered on a case-by-case basis, taking into account the individual patient's needs and circumstances.

From the FDA Drug Label

Of those in response at Week 4 who attained remission during the study, patients in the HUMIRA every other week group maintained remission for a longer time than patients in the placebo maintenance group. Among patients who were not in response by Week 12, therapy continued beyond 12 weeks did not result in significantly more responses. Forty-four percent (44%) of patients had previously lost response or were intolerant to a TNF blocker.

Switching anti-TNF within the class in IBD may be considered for patients who have lost response or are intolerant to another TNF blocker.

• Key points:
  • Patients who had previously received a TNF blocker were allowed to enroll in the study if they had previously had loss of response or intolerance to that TNF blocker.
  • Forty-four percent of patients had previously lost response or were intolerant to a TNF blocker.
  • The study suggests that switching to adalimumab may be effective for patients who have lost response to or are intolerant of another TNF blocker, such as infliximab 2.

From the Research

Switching Anti-TNF within Class in IBD

• Switching within the anti-TNF class is a viable option for patients with high anti-drug antibody (ADAb) levels who have previously benefited from anti-TNF therapy, as ADAb are molecule-specific 3
• For patients with low drug concentrations who are ADAb-negative or display low levels of ADAb, dose escalation is recommended, and if response remains unchanged, switching within class or out of class can be considered 3
• The decision to switch within or out of class should also take into account other factors, including patient preference, age, comorbidities, disease phenotype, extra-intestinal manifestations, and treatment costs 3, 4

Factors Influencing Switching Decision

• Disease behavior/phenotype, disease severity, C-reactive protein, albumin, cytokine expression in serum, previous anti-TNF therapy, and some proteomic markers may have a potential role in predicting response to anti-TNF agents 5
• For vedolizumab, the availability of useful predictive markers seems to be limited, with only some factors showing a limited value, such as the expression of α4β7 integrin in blood and faecal microbiota 5
• No predictive factor has been reported to be helpful in clinical practice for ustekinumab 5

Therapeutic Drug Monitoring

• Therapeutic drug monitoring can help guide treatment optimization and improve patient outcomes by determining drug serum concentrations and the presence of ADAb 3, 6
• Biosimilar agents have been approved for IBDs and are considered equivalent in efficacy to the originator, providing a potential option for patients 6