An entertaining structure at the 2023 Crohn’s & Colitis Congress was "Controversies in IBD: Shark Tank Edition." Here, a panel of “sharks” composed of IBD experts listened to evidence-based presentations of controversial positions in IBD care. They were asked which position statements they would buy and those which they were “out.” Here are a summary of some of the pitches:
The first contestant was IBD legend himself, Dr. Ed Loftus of the Mayo Clinic, pitching the idea of combination biologic therapy upfront for everyone. The premise was that over two-thirds of patients would ultimately have a primary or secondary loss of response to anti-TNF therapy. He cited data efficacy from both the VEGA trial and EXPLORER CD studies. Unfortunately, despite dropping clear data on efficacy without compromising safety, the sharks did not buy in. The first point raised was the importance of finding the right kind of patient, one with significant refractory disease failing conventional therapy and one that would also be willing to take two biologics. A second major theme presented to the sharks was insurance coverage, one of the main hurdles they could foresee in starting a patient on dual-biologic therapy. Dr. Dotson, our pediatric expert on the panel, provided the perspective that, unfortunately, all this data remains limited to adult patients and cannot be extrapolated to the pediatric population at this time. The ultimate consensus around the tank remained that, at this time, there were no buyers until more data came out in the future about dual-biologic therapy and optimal timing and patient demographics for it, we would continue with our current conventional prescribing practices.
Our second contestant was Dr. Ryan Ungaro from Mount Sinai, who pitched the sharks on de-escalating combination therapy to biologic monotherapy after one year in all IBD patients. His first statement was the improved efficacy of combination therapy, seen in the SONIC trial. Dr. Unagro then cited evidence that combination therapy has been associated with increased infection risk and increased cancer risk. The STORI trial established that stopping anti-TNF therapy led to over 50% relapse, so this is not an acceptable option when discussing de-escalation of treatment. Mahumoud et al. demonstrated in a retrospective study of 500 patients, that immunomodulator therapy withdrawal in patients receiving anti-TNF therapy demonstrated no increased loss of response in the one to two years following discontinuation. The prospective DIAMOND2 study also supports the efficacy of de-escalating to biology monotherapy, with no difference in corticosteroid-free clinical remission seen in the group continued on combination therapy (95.5%) compared to the discontinued group (92.9%). Our guest sharks were keen on buying, however, with some vital caveats. It was recommended that patients were optimized before cessation of the immunomodulator (IM) and be in steroid-free, clinical and endoscopic remission for the past year. Dr. Loftus also mentioned the importance of checking a proactive drug level at this point and if the levels were all at borderline, dose optimization of the biologic should be performed before discontinuation of the IM.
Dr. Cynthia Seow, our presenter from the University of Calgary, brought the bold idea that proactive therapeutic drug monitoring is a dead art. She emphasized that the key to care should be treating to target, and not trough, levels. Dr. Seow noted that reactive therapeutic drug monitoring (TDM) is useful as it helps us rationalize real-time management decisions. She also explained that early reactive therapeutic drug monitoring is critical; it gives us information during acute inflammation about drug clearance and how to optimize dosing early on to “put out the fire.” The trouble with practice TDMs, as Dr. Seow mentioned, is that dose adjustments made for a predetermined trough concentration, regardless of disease activity, has not shown to have any improvement in clinical remission. She cited a meta-analysis by Ricciuto et al., which examined nine RCTs. It showed dose adjustments to maintain predetermined trough concentration regardless of disease activity did not improve clinical remission rates at week 48. Additionally, it led to increased costs due to the subsequent dose escalations. The majority of our sharks bought the idea that proactive TDM is not effective, as it was clear the data supported this. They pointed out the importance of semantics by noting that proactive is not equivalent to early reactive levels, which are usually done during the induction period while there is active inflammation, to help optimize drug dosing to ensure adequate maintenance dosing. Several sharks, including our shark working in the pediatric IBD population noted that a week 14 level is often performed during the administration of infliximab for adequate dosing optimization. This comes from the study published by Courbette et al. demonstrating that trough levels of infliximab at week six help predict remission at week 14 in the pediatric population.
Although this was a session fueled with fiery debates, ultimately, several key learning points arose from the discussion for the audience. From Dr. Loftus’s presentation, we learned that it remains too early to advocate for dual-biologic therapy for the masses, and choosing the correct patient is crucial to this strategy. From Dr. Ungaro, we happily bought the idea that we should discontinue immunomodulator therapy in patients on combination therapy as long as they are in clinical and endoscopic remission, ideally for a year. Lastly, Dr. Seow demonstrated the importance of using clinical and laboratory parameters to decide on drug dosing, as the evidence for proactive TDMs in the absence of clinical change is low, with a cost that may be unacceptable for many insurance companies.
Drs. Sharma and Parian have no conflicts of interest to report.
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