P348 Disease trajectories in ulcerative colitis: Early identification of patients with endoscopic remission at Week 52
Schreiber, S.W.(1)*;Danese, S.(2);Dirk, L.(3);Agboton, C.(4);Colombel, J.F.(5);
(1)University Hospital Schleswig-Holstein, Gastroenterology, Kiel, Germany;(2)University Vita-Salute San Raffaele, Gastroenterology, Milan, Italy;(3)Takeda, Takeda, Zurich, Switzerland;(4)Takeda, Takeda, Cambridge- MA, United States;(5)Icahn School of Medicine at Mount Sinai, Gastroenterology, New York- NY, United States;
Background
Clinical understanding of different disease courses in response to targeted therapies in ulcerative colitis (UC) is lacking. Symptom load over time can help to define different trajectories leading to outcome measures at week 52. This post hoc analysis from the GEMINI 1 study of vedolizumab (VDZ) vs placebo for the treatment of moderately to severely active UC1 aimed to define different clinical patterns of response that led to Week 52 endoscopic remission based on daily collection of symptom data: rectal bleeding (RB) and stool frequency (SF).
Methods
RB and SF data, each scored 0 to 3, were extracted from the diary cards of patients who were treated with VDZ up to Week 50, had clinical outcome assessed at Week 52 and had sufficient diary data. From the daily scores, six different daily symptom score rules comprising RB alone or various combinations of RB and SF (Table 1) were derived. Each of the six symptom score rules was then accrued over the time to derive cumulative symptom scores (area under the curve [AUC]). The AUCs at Weeks 6, 10, 14 and 22 for each rule were evaluated for sensitivity and specificity to predict endoscopic remission at Week 52, which was defined as Mayo endoscopic subscore of ≤1 point.
Results
Of the 895 pts included in the GEMINI 1 study, 217 pts were treated with VDZ, had sufficient RB and SF data and Week 52 outcome data. Of these, 157 (72.4%) achieved endoscopic remission at Week 52. Rule 4, with a score of 0 if both RB=0 and SF≤1 or 1 if not, was consistently better at predicting response at Week 52, i.e., had largest area under the receiver-operator characteristic (ROC) curve (Week 10 and Week 14 shown in Table 2). Area under ROC curve for Rule 4 was 0.7317 (0.6578, 0.8057) and 0.7534 (0.6810, 0.8258) at Week 10 and Week 14, respectively (Fig 1). Rule 4 had better predictive performance than the use of RB Mayo score (RB1) alone or the simple dichotomization (RB2, 0 if RB≤1, 1 if RB >1) [Table 2]. AUCs for Rule 4 differed between pts with vs without endoscopic remission at Week 52, with differences evident as early as Week 10: median AUC=41 for pts with endoscopic remission vs 70 for pts without (Fig 2).
Conclusion
The daily collection of RB and SF symptoms during the first weeks of therapy with VDZ identifies patients with a high likelihood for endoscopic emission at Week 52. Early clinical symptom change is a simple method for tight monitoring of patients with UC. The identification of preferential responder populations in which marked reduction of suffering are combined with hard endpoints could help in establishing treatment optimization algorithms for targeted therapies.
References
1. Feagan BG et al. (2013) N Engl J Med 369:699–710
