The thorny issue of proactive therapeutic drug monitoring (TDM) for anti-TNF therapy in IBD patients was the subject of a vociferous debate at DDW 2018, ending in no agreement.
While noting that Australian clinicians have recently issued a consensus statement offering cautious support for proactive TDM in some situations, the session at DDW 2018 was marked by a distinct polarisation over the limited evidence to support monitoring of infliximab or adalimumab, let alone the non-TNF agents such as ustekinumab and vedolizumab used in IBD.
Most clinicians agreed with the 2017 American Gastroenterology Association statement that backed reactive TDM in patients failing treatment in order to guide decision‐making.
However there was a clear divergence of opinion when it came to the AGA’s cautionary lack of endorsement of proactive testing.
Professor Hans Herfarth, co-director of the University of North Carolina Multidisciplinary Center for IBD Research and Treatment, noted that the AGA cautionary approach was based on trials such as TAXIT and TAILORIX that did not find a significant difference in clinical and biochemical remission between proactive TDM-based dosing and dosing based on symptoms.
However Dr Adam Cheifetz, director of the Center for Inflammatory Bowel Disease at Beth Israel Deaconess Medical Center made a strong argument in favour of proactive TDM, saying it should now be routine to optimise management of IBD with TNF inhibitors.
He pointed to findings presented during the meeting showing that low concentrations of adaluminab at week 4 of treatment predicted immunogenicity and poor response.
Dr Cheifetz added that the TAXIT and TAILORIX trials were flawed or not designed to assess TDM, and this meant they could not be considered to be negative trials for proactive TDM. In fact, they showed that only 25% of patients treated with infliximab would be in remission without dose intensification, he pointed out.
He also noted a recent survey of more than 400 gastroenterologists which showed more than one in three were already proactively checking their patients’ drug levels and antibody levels. The main barrier for clinicians using proactive TDM was lack of reimbursement and costs to patients rather than clinicians’ concerns about the level of evidence, he argued.
“If the barriers were removed, more clinicians would test proactively, he said.
But Prof Herfarth said that despite some suggestions of benefit, there were still too many unanswered questions about proactive TDM.
To reach a consensus it will be necessary to agree on the right time points for proactive TDM such as during induction or maintenance, and how often TDM should be performed, he suggested. There are also unanswered questions about the optimal trough concentrations for desired outcomes, and whether these should be remission or muscosal healing, he added.
“The field is very fast moving, there’s a lot of new data. I think we have to look at that and go back and revitalise the 2017 AGA consensus statement,” he concluded.
The 2017 consensus statement drawn up by Australian clinicians recommends proactive testing after successful induction at week 14, in those where a drug holiday is contemplated, and periodically during remission “if the results are likely to impact management.”