Consensus Statements Support TDM-Guided Anti-TNF Therapy in IBD

Anti—tumor necrosis factor (TNF) agents, including infliximab and adalimumab, have revolutionized the treatment of inflammatory bowel disease (IBD). However, primary nonresponse (defined as no initial clinical benefit to therapy) and secondary loss of response (defined as a loss of response after an initially favorable outcome) are common, with resulting adverse outcomes. Among infliximab- and adalimumab-treated patients with IBD, primary nonresponse occurs in 10% to 30% of patients, while secondary loss of response occurs in 23% to 46% of patients by 12 months. Anti-TNF drugs are expensive, and there are a limited number of choices for IBD treatment, highlighting the need to use every existing agent optimally. Recently, anti-TNF dosing guided by therapeutic drug monitoring (TDM) has emerged as a potential strategy to optimize treatment and maximize benefit from these drugs, but there has been no formal consensus about TDM-guided anti-TNF dosing.

Recently, a group of 25 IBD experts from the Australian Inflammatory Bowel Disease Consensus Working Group and other international experts published recommendations on TDM in anti-TNF therapy that supported the role of TDM in optimizing treatment with anti-TNF agents for patients with IBD, particularly in situations of treatment failure.

The committee recommends TDM of anti-TNF agents upon treatment failure, following successful treatment induction, and when contemplating a drug holiday. However, the group said there is inconsistent evidence for proactive TDM, and therefore advise that TDM should be performed for patients in stable remission only if results are likely to impact clinical management. The assembly’s statement was published on October 13, 2017, in Alimentary Pharmacology and Therapeutics.

The statement presents an appropriate therapeutic range for infliximab and adalimumab that was delineated to make the guidelines more clinically applicable. The statement also makes the following recommendations:

• To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3 - 8 µg/mL and 5 - 12 µg/mL are deemed to be appropriate; this range may differ among disease phenotypes or treatment endpoints
• In cases of treatment failure, TDM may identify mechanisms to guide subsequent decision making
• In stable clinical response, TDM-guided dosing may help to avoid future relapse
• Data indicate that drug-tolerant and anti-drug antibody assays do not offer an advantage over drug-sensitive assays
• Further data are needed before a recommendation is made for TDM for other types of biologic agents

In order to reach their conclusions, the experts examined scenarios concerning when TDM of anti-TNF agents should be performed, the general approach to patients with symptoms of active disease while receiving anti-TNF therapy, the interpretation of TDM results in patients with confirmed active inflammatory disease who are on anti-TNF therapy, interpreting TDM results among patients in clinical remission who are on anti-TNF therapy, target drug trough levels, anti-drug antibodies, and TDM for other types of biological agents as well as future therapies.

The final recommendations were reached through a consensus process using a modified Delphi technique that used 3 iterations. The panelists agreed on the level of evidence and grade of recommendation according to Australian National Health and Medical Research Council guidelines, and all members of the delegation approved the final draft recommendations prior to submission for publication.

“In conclusion, TDM of anti-TNF agents is an important component of personalized therapy in IBD,” the experts state. “These consensus statements should provide a practical guide to applying TDM of anti-TNF agents in treatment optimization for IBD patients.”