Vedolizumab is effective and safe in post-IPAA chronic pouchitis: The phase 4 EARNEST trial

The phase 4 EARNEST trial results have demonstrated a significant clinical improvement of pouchitis symptoms and endoscopic findings within 14 weeks of vedolizumab among ulcerative colitis (UC) patients who had undergone restorative proctocolectomy with ileal pouch-anal anastomosis (RP-IPAA) and developed pouchitis, further supporting the use of vedolizumab as a treatment for chronic pouchitis.2 

UC is the most common form of inflammatory bowel disease worldwide.3 It is an idiopathic inflammatory condition of the colon which results in diffuse friability and superficial erosions of the colonic walls.3 Up to 35% of UC patients require surgical intervention, with RP-IPAA being the gold standard.1 However, up to half of patients undergoing RP-IPAA develop pouchitis, and around a fifth of them will turn into chronic condition.2 Pouchitis is an idiopathic inflammation of the pouch and is the most common long-term complication in patients who have received RP-IPAA.2 It is characterized by increased stool frequency, abdominal pain, and fecal urgency, thus leading to impaired quality of life.2 Treatment is largely empirical with a lack of randomized controlled trials.4 For patients who are refractory to antibiotics, studies have suggested that tumor necrosis factor (TNF) antagonists such as vedolizumab may be an effective treatment.2  

EARNEST was a recent phase 4, multicenter, double-blind, randomized, placebo-controlled trial that evaluated the safety and efficacy of vedolizumab among post-RP-IPAA patients over a 34-week treatment period.2 A total of 102 adult patients with ≥3 recurrent pouchitis episodes 1 year prior to screening, and active chronic pouchitis defined by the modified Pouchitis Disease Activity Index (mPDAI) of ≥5 and endoscopic domain subscore ≥2 were recruited.2 Eligible patients were randomized 1:1 to receive intravenous (IV) vedolizumab 300mg or placebo on day 1 as well as weeks 2, 6, 14, 22, and 30.2 All patients received concomitant oral ciprofloxacin 500mg twice daily throughout weeks 1-4.2 Additional antibiotic therapy was permitted after week 14, and that oral glucocorticoids were permitted only if they were taken at a stable dose at least 4 weeks prior to randomization.2 

The primary endpoint was mPDAI-defined remission at week 14, which was defined as a score of ≤4 with ≥2 improvements from baseline.2 Results showed that 31% of patients (n=16) treated with vedolizumab had achieved mPDAI-defined remission compared with 10% in the placebo arm (n=5) with an adjusted difference of 22% (95% CI: 6.5-37; p=0.007).2 The secondary endpoints included mPDAI-defined remission at week 34, and mPDAI-defined partial response at week 14 and 34 (i.e., defined as a reduction of ≥2 points from baseline).2 The percentage of patients who had mPDAI-defined remission at week 34 remained higher in the vedolizumab group, which slightly increased to 35% of patients (n=18) on vedolizumab compared with 18% in the placebo arm (n=9), the between-group difference was 17% (95% CI: 0%-35%).2 Similarly, a higher proportion of patients achieved the secondary mPDAI-defined response in the vedolizumab group with a difference of 30% (95% CI: 8%-48%) and 22% (95% CI: 2%-40%) assessed at week 14 and week 34, respectively.2 Safety was also assessed in the study, in which serious adverse events (SAEs) occurred in 6% of patients (n=3) in the vedolizumab arm and 8% in the placebo arm (n=4), respectively.

In this study, vedolizumab has been proven effective in inducing remission and reducing symptoms of chronic pouchitis among patients who had undergone RP-IPAA.2 However, longer-term data with regard to both the efficacy and safety of vedolizumab in this patient population are still warranted.

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