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.² 

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.²