Meeting NewsPerspective

Predictors of response to Stelara identified in Crohn’s

SAN ANTONIO — Researchers were able to identify predictors of response to Stelara in Crohn’s disease, and subsequently model those predictors into a decision-support tool model that helped predict both achievement of clinical remission and rapidity with which symptoms reduced.

“Several studies have looked and identified potential predictors of treatment outcomes, but the optimal approach to integrating these predictors and integrating the therapy into practice is uncertain and unknown,” Parambir S. Dulai, MBBS, a gastroenterologist at UC San Diego Health, said during his presentation at the American College of Gastroenterology Annual Meeting. “We wanted to create an easy to use prediction model that is a support tool to guide the use of ustekinumab in Crohn’s disease within the emerging paradigm of treatment options.”

The ability to develop a prediction and decision support tool served as the primary outcome.

Secondary outcomes included whether the clinical decision support tool could predict Stelara (ustekinumab, Janssen) exposure, rapidity of onset of action and endoscopic remission.

The study comprised 781 patients with Crohn’s disease treated with ustekinumab during the induction and maintenance phases of the UNITI trial.

Patients were included if they received ustekinumab intravenously during the induction phase and subcutaneously during the maintenance phase.

There was no restriction in dosing arm and patients were not restricted based on their induction response status.

Participants exposed to placebo were excluded from the study. Clinical remission at week 16 served as the primary outcome of interest.

Clinical remission was defined as a CDAI score of less than 150 as defined by the primary trial.

In the derivation analysis, baseline albumin g/L (HR = 1.041; 95% CI, 1.019–1.063), no prior smoking history (HR = 1.233; 95% CI, 0.995–1.527), absence of baseline actively draining fistula (HR = 1.33; 95% CI, 0.906–1.952), absence of prior bowel surgery (HR = 1.425; 95% CI, 1.14–1.781), and absence of prior exposure to tumor necrosis factor antagonist (HR = 1.591; 95% CI, 1.214–1.9), were associated with achieving clinical remission by week 16 of treatment.

Rates of clinical remission at weeks 3, 6, 8, and 16 were significantly higher in the high probability group vs. the intermediate and low probability groups. The high probability group had a significantly greater reduction from baseline in CDAI compared with the intermediate and low probability groups at week 8 (high vs. intermediate, 94 vs. 54, P < 0.0001; high vs. low, 94 vs. 40, P < 0.0001) and week 16 (high vs. intermediate, 155 vs. 112, P < 0.0001; high vs. low, 155 vs. 84, P < 0.0001).

“There was a statistically significant association between the predicted probability groups, trough exposures and efficacy,” Dulai said. “Patients in the low probability group did possess several characteristics that are generally refractory to most medical therapies, so there could be some consideration in these patients and given the low trough concentrations there's some potential opportunities there for optimization and we are undergoing an external validation of this in a routine practice through the SUCCESS Consortium which is now finalized and going through its analysis.” – by Ryan McDonald

Reference:

Dulai PS, et al. Abstract 39. Presented at: American College of Gastroenterology Annual Meeting; Oct. 25-30, 2019; San Antonio.

Disclosure: Dulai reports no relevant financial disclosures.

SAN ANTONIO — Researchers were able to identify predictors of response to Stelara in Crohn’s disease, and subsequently model those predictors into a decision-support tool model that helped predict both achievement of clinical remission and rapidity with which symptoms reduced.

“Several studies have looked and identified potential predictors of treatment outcomes, but the optimal approach to integrating these predictors and integrating the therapy into practice is uncertain and unknown,” Parambir S. Dulai, MBBS, a gastroenterologist at UC San Diego Health, said during his presentation at the American College of Gastroenterology Annual Meeting. “We wanted to create an easy to use prediction model that is a support tool to guide the use of ustekinumab in Crohn’s disease within the emerging paradigm of treatment options.”

The ability to develop a prediction and decision support tool served as the primary outcome.

Secondary outcomes included whether the clinical decision support tool could predict Stelara (ustekinumab, Janssen) exposure, rapidity of onset of action and endoscopic remission.

The study comprised 781 patients with Crohn’s disease treated with ustekinumab during the induction and maintenance phases of the UNITI trial.

Patients were included if they received ustekinumab intravenously during the induction phase and subcutaneously during the maintenance phase.

There was no restriction in dosing arm and patients were not restricted based on their induction response status.

Participants exposed to placebo were excluded from the study. Clinical remission at week 16 served as the primary outcome of interest.

Clinical remission was defined as a CDAI score of less than 150 as defined by the primary trial.

In the derivation analysis, baseline albumin g/L (HR = 1.041; 95% CI, 1.019–1.063), no prior smoking history (HR = 1.233; 95% CI, 0.995–1.527), absence of baseline actively draining fistula (HR = 1.33; 95% CI, 0.906–1.952), absence of prior bowel surgery (HR = 1.425; 95% CI, 1.14–1.781), and absence of prior exposure to tumor necrosis factor antagonist (HR = 1.591; 95% CI, 1.214–1.9), were associated with achieving clinical remission by week 16 of treatment.

Rates of clinical remission at weeks 3, 6, 8, and 16 were significantly higher in the high probability group vs. the intermediate and low probability groups. The high probability group had a significantly greater reduction from baseline in CDAI compared with the intermediate and low probability groups at week 8 (high vs. intermediate, 94 vs. 54, P < 0.0001; high vs. low, 94 vs. 40, P < 0.0001) and week 16 (high vs. intermediate, 155 vs. 112, P < 0.0001; high vs. low, 155 vs. 84, P < 0.0001).

“There was a statistically significant association between the predicted probability groups, trough exposures and efficacy,” Dulai said. “Patients in the low probability group did possess several characteristics that are generally refractory to most medical therapies, so there could be some consideration in these patients and given the low trough concentrations there's some potential opportunities there for optimization and we are undergoing an external validation of this in a routine practice through the SUCCESS Consortium which is now finalized and going through its analysis.” – by Ryan McDonald

Reference:

Dulai PS, et al. Abstract 39. Presented at: American College of Gastroenterology Annual Meeting; Oct. 25-30, 2019; San Antonio.

Disclosure: Dulai reports no relevant financial disclosures.

    Perspective
    Miguel Regueiro

    Miguel Regueiro

    This was an interesting study looking at a clinical prediction model for ustekinumab in the UNITI-1 and UNITI-2 trials. The researchers aimed to determine if their model could predict which patients were more likely to respond to ustekinumab.

    The researchers split the model into those who were a high likelihood to respond and those who were a low likelihood. Essentially what they found was that having a higher baseline albumin, not smoking, not having fistula, not having had a surgery and not having prior anti-TNF were associated with more likely response.

    This indicates that using ustekinumab as first-line therapy for these patients with Crohn's disease who had not been on a biologic before and were non-smokers, had no fistula, and only luminal, inflammatory disease had a much better response than those that had these other risk factors.

    Additionally, the researchers looked at trough concentration levels of patients receiving ustekinumab. Probably not surprisingly they found that patients with higher trough concentration levels had better outcomes and better predictors of response. Which gets to the concept that if a patient has good levels of circulating medicine, then they would be more likely to respond.

    From a practical standpoint, this study is very interesting, but I’m not sure that this changes my approach to my positioning of ustekinumab for IBD. Meaning, I’d still use ustekinumab whether the patient did not have risk factors or did have such risk factors as fistula, cigarette smoking, or prior surgery. I think the future will be more about precision medicine and medication choice based on certain biomarkers. It’s possible this would improve our treatment responses and “the right medication for the right patient.”

    • Miguel Regueiro, MD
    • Chairman, Department of Gastroenterology, Hepatology and Nutrition
      Cleveland Clinic

    Disclosures: Regueiro reports consulting for AbbVie, Janssen, Pfizer, Takeda, Genentech, Gilead, Salix, Prometheus, Celgene.

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