Meeting NewsPerspective

Therapeutic drug monitoring program improves clinical outcomes in pediatric IBD

SAN DIEGO — Implementing a practice-wide therapeutic drug monitoring program may help improve several significant clinical outcomes in children with inflammatory bowel disease, according to study results presented at Digestive Disease Week.

In his presentation, John L. Lyles, MD, of the division of gastroenterology, hepatology and nutrition at Cincinnati Children’s Hospital Medical Center (CCHMC), said that therapeutic drug monitoring (TDM) has been beneficial for the treatment of patients with IBD, but evidence to support expanding and implementing a larger scale TDM program has been limited.

CCHMC instituted Remicade (infliximab, Janssen) and Humira (adalimumab, AbbVie) TDM guidelines in 2014 that included recommendations to monitor drug levels after induction and annually, while adjusting dose or frequency to achieve a drug level of more than 5 g/mL. Researchers compared outcomes in patients who started therapy before the TDM program was implemented (pre-TDM, 2011 to 2013; n = 108) and after (post-TDM, 2014 to 2017; n = 206) with a one-year washout period. They assessed sustained clinical remission (SCR), defined as physician global assessment of quiescent from 22 to 52 weeks and off corticosteroids at 52 weeks. Both groups had similar baseline characteristics, except for expected higher starting infliximab maintenance dose in the post-TDM group.

Lyles and colleagues found that 59% of patients in the post-TDM group achieved SCR compared with 42% in the pre-TDM group (risk difference 17.6%; 95% CI, 5.4-29%).

The TDM program also helped reduce incidence of high titer anti-drug antibodies and reduce anti-TNF cessation related to anti-drug antibodies.

“The implementation of a proactive anti-TNF therapeutic drug monitoring quality improvement program was not only feasible, but also improved sustained clinical remission rates, reduce incidence of high-tier anti-drug antibodies and reduced cessation due to antidrug antibodies,” Lyles concluded. – by Alex Young

Reference:

Lyles JL, et al. Abstract 303. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosures: Lyles reports no relevant financial disclosures. Please see the meeting disclosure index for all other authors’ relevant financial disclosures.

SAN DIEGO — Implementing a practice-wide therapeutic drug monitoring program may help improve several significant clinical outcomes in children with inflammatory bowel disease, according to study results presented at Digestive Disease Week.

In his presentation, John L. Lyles, MD, of the division of gastroenterology, hepatology and nutrition at Cincinnati Children’s Hospital Medical Center (CCHMC), said that therapeutic drug monitoring (TDM) has been beneficial for the treatment of patients with IBD, but evidence to support expanding and implementing a larger scale TDM program has been limited.

CCHMC instituted Remicade (infliximab, Janssen) and Humira (adalimumab, AbbVie) TDM guidelines in 2014 that included recommendations to monitor drug levels after induction and annually, while adjusting dose or frequency to achieve a drug level of more than 5 g/mL. Researchers compared outcomes in patients who started therapy before the TDM program was implemented (pre-TDM, 2011 to 2013; n = 108) and after (post-TDM, 2014 to 2017; n = 206) with a one-year washout period. They assessed sustained clinical remission (SCR), defined as physician global assessment of quiescent from 22 to 52 weeks and off corticosteroids at 52 weeks. Both groups had similar baseline characteristics, except for expected higher starting infliximab maintenance dose in the post-TDM group.

Lyles and colleagues found that 59% of patients in the post-TDM group achieved SCR compared with 42% in the pre-TDM group (risk difference 17.6%; 95% CI, 5.4-29%).

The TDM program also helped reduce incidence of high titer anti-drug antibodies and reduce anti-TNF cessation related to anti-drug antibodies.

“The implementation of a proactive anti-TNF therapeutic drug monitoring quality improvement program was not only feasible, but also improved sustained clinical remission rates, reduce incidence of high-tier anti-drug antibodies and reduced cessation due to antidrug antibodies,” Lyles concluded. – by Alex Young

Reference:

Lyles JL, et al. Abstract 303. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosures: Lyles reports no relevant financial disclosures. Please see the meeting disclosure index for all other authors’ relevant financial disclosures.

    Perspective
    Joel R. Rosh

    Joel R. Rosh

    All of us have recognized an observation frequently attributed to former U.S. Surgeon General C. Everett Koop, MD, which is, “Medications tend not to work well for people who don’t take them.”

    The analogy to that with biologic therapies is that biologics don’t work well in those patients who are underdosed. If I take a medication, whether it be by injection or infusion, and by the time it rolls around for me to take my next dose, there is an inadequate level of drug circulating from the last dose, I’m less likely to have a good outcome compared with someone who has enough drug delivered to maintain an efficacious level throughout this cycle from one dose to the other. This realization birthed the whole idea of therapeutic drug monitoring, or TDM.

    Within the TDM world there are those who advocate for reactive testing. That is, when a patient is not responding or has lost response to an agent, let me get a drug level and see if this is a dosing issue. Counter to this reactive strategy, there are those who advocate for the use of routine proactive testing to best personalize dosing and assure the maintenance of adequate drug levels. The devil is always in the details, and we don’t necessarily know the exact best target for drug level or the best time to obtain the level or how often to do it. Therefore, the concepts are pretty clear and it’s the logistics that still need to be worked out.

    In this study, the researchers target was 5 µg/mL, which for adalimumab is below the AGA guidelines of 7.5 µg/mL. The AGA guidelines for infliximab are 5 µg/mL, so they were in compliance with that. Although there are a lot of data that have come out since those guidelines were published that suggest a level of 10 µg/mL may be more efficacious with infliximab and it also depends on the phenotype of the patient as those with perianal disease may even need higher levels more like 12 µg/mL or 15 µg/mL.

    In any event, the goal here was 5 µg/mL and as a quality improvement project started in 2014, drug levels were obtained after induction and then annually. The researchers then compared clinical outcomes in 108 patients from 2011 to 2013 to those in almost twice as many patients (n = 206) from 2014-2017.

    They found that implementation of a proactive TDM program was feasible in a large pediatric IBD center and that their drug level monitoring program was associated with higher rates of clinical remission. It may be possible that a higher drug target level would have resulted in an even larger treatment effect and this remains a question to be answered, although the literature that is available suggests that would be the case. This was a study of interest in that it demonstrated that in a large center, a consensus to change treatment practice can improve the quality of care. By effecting a change in practice across a variety of providers, better treatment outcomes were realized.

    • Joel R. Rosh, MD, FAAP, FACG, AGAF
    • Director, Pediatric Gastroenterology
      Vice Chairman, Clinical Development and Research Affairs
      Goryeb Children’s Hospital
      Professor of Pediatrics, Icahn School of Medicine at Mount Sinai

    Disclosures: Rosh reports he serves as a consultant to AbbVie, Eli Lilly, Janssen and Pfizer. Rosh also reports receiving grant and research funding from AbbVie and Janssen.

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