Rates of histologic remission, minimal histologic disease activity and combined histologic plus endoscopic outcomes in ulcerative colitis (UC) treatment were higher with vedolizumab than adalimumab, according to the recent VARSITY trial.¹ The results were consistent with previously reported findings of higher rates of clinical remission and endoscopic improvement with vedolizumab vs. adalimumab.²

UC is a chronic inflammatory disorder of the large bowel characterized by bloody diarrhea, abdominal pain and fatigue.3 Biologic therapies are widely used to induce and maintain clinical remission for moderate-to-severe UC patients.^3,4 However, there is relatively dearth of trials comparing the effectiveness of different biologic agents.² The recent VARSITY trial was a phase 3b, double-blind, double-dummy, multicentre, randomized controlled trial designed to address this aspect.^1,2 The results have shown superior clinical remission and endoscopic improvement at week 52 with vedolizumab compared with adalimumab for the treatment of UC.^1,2

According to the European Crohn’s and Colitis Organization (ECCO), the determination of mucosal healing and treatment response should be supported by both endoscopic and histologic assessment of the mucosa.^1,5 This is because endoscopic changes alone do not necessarily reflect quiescent microscopic disease, and complete resolution of mucosal inflammation can only be confirmed by histologic assessment.¹ Histological outcomes are also indicators to predict hospitalization, corticosteroid use, exacerbation of UC, and the risk of advanced colorectal neoplasia.¹

Patients eligible in the VARSITY trial were adults aged 18-85 years old, with moderate-to-severe UC, as defined with a score of 6-12 on the Mayo Scale and a sub-score of 2 on the endoscopic components of the Mayo scale.¹ Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in, but capped at 25%.¹ Patients who had no response to conventional treatments were also eligible.¹ In the trial, 769 participants were randomized to receive either vedolizumab (n=383) or adalimumab (n=386) for 52 weeks with a final safety follow-up visit at week 68.¹ The patients in the vedolizumab group received 300mg vedolizumab intravenously on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo),¹ while the patients in the adalimumab group received 40mg adalimumab subcutaneously every 2 weeks after a total loading dose of 160mg at week 1 and 80mg at week 2, until week 50 (plus infusions of placebo).¹ Dose escalation was not permitted.¹ Histologic remission was defined as Geboes grade <2 and RHI score <2.1 minimal histological disease activity was defined as Geboe grade ≤3.1 and RHI score<4.¹

At week 52, more patients in the vedolizumab group than in the adalimumab group achieved histologic remission as determined by the Geboes Index score (29.2% vs. 8.3%; difference: 20.9%; 95% CI: 15.6%-26.2%) and the RHI score (37.6% vs. 19.9%; difference: 17.6%; 95% CI: 11.3%-23.8%).¹ Also, more patients in the vedolizumab group than in the adalimumab group achieved minimum histologic disease activity as determined by Geboes Index score (45.7% vs. 30.8%; difference: 14.8%; 95% CI: 8.0%-21.5%) and the RHI score (42.3% vs. 25.6%; difference: 16.6%; 95% CI: 10.0%-23.1%).¹

There was also moderate agreement between endoscopic improvement and histologic remission with the RHI score (κ=0.47; 95% CI: 0.42-0.52), as well as the Geboes grades (κ=0.36; 95% CI: 0.31-0.41).¹ This pattern was the same as the minimal histologic disease activity.¹ Since the association between histological outcomes and endoscopic improvement was greater with the RHI scoring system compared with the Geboes Index score,¹ RHI should be recommended as the better histological scoring system to compare treatment efficacies in trials.¹ 

Overall, vedolizumab was proven to be superior to adalimumab in achieving the histologic remission and minimal histologic disease activity in patients with moderate-to-severe UC.¹