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Editorial: is vedolizumab effective for perianal Crohn's disease?

Perianal disease poses a significant clinical challenge among Crohn's disease (CD) patients. With a prevalence of 20%-30%, it causes considerable morbidity and increases the risk of anal canal carcinoma.1,2 Alongside antibiotics, anti-TNFs and mainly infliximab, serve as firstline therapies and allogeneic adipose-derived stem cell treatment is being currently developed worldwide.3 However, among CD patients with perianal disease, clinical and radiological remission rates are considerably lower than for non-fistular disease, with 30%-50% and 20%-30% remission respectively.4 Although vedolizumab has been proven safe and effective as a firstand second-line therapy for moderate-to-severe CD, scarce data exist as to its efficacy for perianal disease.5-7 Chapuis-Biron and colleagues have conducted a multicentre study of 151 patients in order to address this important clinical question.8 Of the 151 patients, 102 (68%) had active perianal disease and 49 had inactive disease at enrollment (32%). Among the former, 68 (66.7%) discontinued therapy (median 33 weeks) and only 23 (22.5%) improved clinically. Among the latter, 30.5% experienced recurrence of perianal disease under vedolizumab therapy (median 21.9 weeks). The authors found that the number of prior biologics and antibiotic therapy at initiation were negative predictive factors. We believe this pivotal study has several strengths. First and foremost, this is the largest cohort to analyse the outcomes of vedolizumab therapy among perianal CD patients. In an exploratory analysis of the GEMINI2 trial, the outcome of vedolizumab therapy was assessed in 32 patients with perianal fistulae. By week 14, 11 (28%) had fistula closure, compared with 2 patients (11%) treated with placebo after induction therapy. This study also demonstrated antibiotic therapy as a negative predictor of fistula closure.7,9 Another strong point of the study is its subanalysis for active and inactive fistular disease. Thereby, two different clinical scenarios have been assessed— the rates of response/remission under vedolizumab therapy and the risk for perianal disease flare-up. However, response rates have not been subanalysed with regard to severity of perianal lesions. Although possibly limited by patient number, this could add some fine-tuning as to the effectiveness of vedolizumab for mild-to-moderate vs severe perianal lesions. Interestingly, the authors point out that 45 (44.1%) of patients received concomitant immunomodulators, which was not found to correlate with therapy success. These findings go in line with previous publications, which have not found a clinical benefit for combination therapy among vedolizumab therapy patients.9 It is of note that the authors have not assessed concomitant steroidal therapy as a possible predictor of therapy outcome, which should be addressed in future studies. Furthermore, in the current study, the measures of outcome have been clinical and radiological parameters related to perianal fistulas and vedolizumab serum levels have not been included. As higher vedolizumab trough levels have been associated with future favourable outcome,10 it would be interesting to explore whether higher vedolizumab trough levels at induction could predict improvement of perianal fistulas. To conclude, there is an unmet need for effective therapies for perianal CD. Future studies ought to better define the efficacy of vedolizumab in this regard and to explore possible combination therapies with adipose-derived stem cell injections and perhaps even anti-TNFs.