Clinicians are a step closer to being able to confidently and effectively use therapeutic drug monitoring to maximise the longevity and efficacy of anti-TNF agents for IBD patients.

The Australian Inflammatory Bowel Disease Association (AIBDA), a branch of the Gastroenterological Society of Australia (GESA), is currently in the final stages of preparing consensus statements on the appropriate use and interpretation of therapeutic drug monitoring (TDM) for anti-TNF agents.

The statements are expected to be published later this year, however GESA AGW 2017 delegates were given a sneak peek at the conference on the Gold Coast today.

One of key authors of the consensus statements, Dr Nikola Mitrev, a research student at Sydney University’s Medical School, has been closely involved with its development and is using it for his thesis work.

Presenting an overview to delegates, he said TDM had emerged as a valuable means of optimising anti-TNF agent use in IBD. However, the vast majority of gastroenterologists had struggled with it for a number of reasons, including access, cost and the lack of clear guidelines about when to test and how to interpret the results.

“These consensus statements are quite important in guiding gastroenteologists of when to perform the tests and how to interpret the results and act on them,” Dr Mitrev told the limbic.

The statements will address both reactive TDM (for patients failing treatment) as well as proactive TDM (for patients responding to treatment) with algorithms developed for both categories. Dr Mitrev said data is more robust for reactive TDM, however there is data to support proactive TDM as well.

“By intervening early we hope that we can protect drug therapy for longer by reducing the risk of secondary loss-of-response,” he said.

The direction for proactive TDM was less clear, and was recommended to be used shortly after successful induction of remission.

“You want to avoid disease flares and protect response to these medications,” Dr Mitrev said.

He conceded that it was still very early days in the use of TDM, particularly given the mixed evidence for proactive TDM.

“We do need more studies, particularly prospective interventional studies,” he said.

“The issue with cross-sectional studies is it is not clear if low anti-TNF drug levels lead to disease relapse, or if disease-relapse leads to low drug levels due to increased drug clearance in high inflammatory states.”

“The recommendations we make are only as good as the data we have.”

Professor Rupert Leong, a senior staff specialist gastroenterologist, Director of Endoscopy and Head of the Inflammatory Bowel Disease Service at Concord Hospital, Clinical Professor of Medicine at University of Sydney and UNSW, and founding director of IBD Sydney, Australia, was the other key author of the statements and has overseen the project from the beginning.

He told the limbic that TDM had an important role to play in the care plan for patients.

“This indeed can revolutionise the way we use biological agents as we have developed algorithms that are evidence-based with support from the Australian IBD gastroenterologists,” he said.

Once published, the consensus statements are expected to play a key role in AIDBA’s lobbying for MBS rebates for TDM of anti-TNF agents.

Conjoint Associate Professor Susan Connor, senior staff specialist at Liverpool Hospital’s Department of Gastroenterology and Hepatology, and a member of the steering committee overseeing the consensus statements, has been particularly vocal on the issue.

She told delegates at last year’s AGW that therapeutic drug monitoring should play an important role in determining and maintaining the most optimal dose of anti-TNF agents for IBD patients, but needed MBS rebates to be more accessible.

Professor Connor said monitoring of infliximab drug levels was invaluable in the management of patients with IBD and there was more than just weight to consider when establishing the correct dosage for each patient. Gender, BMI, abdominal obesity, inflammatory burden and C-reactive protein (CRP) levels also play a role.

Drug concentration is also influenced not only by dose but also by how the drug is absorbed, distributed, metabolised, and eliminated by the body, and this will vary between individuals.

“One size doesn’t fit all and one dosage doesn’t fit all,” she told the limbic last year. “Each person’s body deals with the drug in a different way and that’s where TDM comes in.”

Professor Connor said achieving optimal therapeutic drug concentration was also associated with improved mucosal healing and reduced CRP levels.

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