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
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.