New consensus statements for therapeutic drug monitoring in patients receiving anti-TNF agents for their IBD will help optimise patient outcomes and rationalise use of the costly agents.
The panel of Australian, New Zealand, US and Canadian experts agreed on 22 of the 24 statements drafted after an extensive literature review and modified Delphi process.
They agreed that therapeutic drug monitoring had most utility following successful treatment induction, when considering drug holidays and in treatment failure.
Lead author Professor Rupert Leong, from the Concord Hospital IBD Service, told the limbic monitoring was appropriate soon after successful indication to confirm a therapeutic drug level but not periodically during clinical remission unless the findings would affect management.
Therapeutic drug monitoring could also guide clinical decision-making in situations of primary non-response and secondary loss of response.
The panel determined dose escalation should only occur after confirming active inflammation.
“A lot of doctors are giving increased doses when patients complain of symptoms without finding out why. We need to have objective measures of inflammation such as faecal calprotectin, sigmoidoscopy or colonoscopy,” Professor Leong said.
The panel agreed adherent patients with confirmed active inflammation, sub-therapeutic drug trough levels and no detectable anti-drug antibodies should have dose escalation of their anti-TNF.
However patients with confirmed inflammation and therapeutic drug trough levels were more likely to have pharmacodynamic failure and should be switched out of class.
Professor Leong said drug holidays were possible for patients travelling to third world countries or having major surgery to avoid the risk of infection with immunosuppression.
“And when we stop treatment we might check drug levels because it’s possible people have no drugs on board; they may be clinically well for long periods of time and not relying on the drug.”
“We can then make the decision if there is a need to reintroduce treatment or not. It could be the disease naturally went into longstanding remission independently of the drug.”
Professor Leong said the relevance of anti-drug antibodies was becoming clearer over time.
“And they are not as detrimental as we initially thought. It turns out there are transient antibodies and these can be easily managed by continuing treatment or in some cases increasing the dose.”
The panel recommended drug-sensitive assays – commonly ELISA tests or radioimmunoassay (RIA) – were less expensive than drug-tolerant assays and just as reliable.
They also agreed that more data was required before recommending routine therapeutic drug monitoring in non-anti-TNF biological agents such as ustekinumab and vedolizumab.
“This is a dynamic field and guidance is not yet set in stone. Proactive monitoring will be increasingly adopted, and we also need to be vigilant of overall costs and adopt more cost-conscious ways of using the drugs.”