{'fraction_non_alphanumeric': 0.03364699173082407, 'fraction_numerical': 0.017964071856287425, 'mean_word_length': 5.1978798586572434, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Editorial: vedolizumab in inflammatory bowel diseases—less is more?

Optimal strategies to de-escalate vedolizumab maintenance therapy for patients with inflammatory bowel disease (IBD) in stable clinical remission have not been adequately investigated. Danese et al reported treatment persistence and safety results among 311 IBD patients enrolled in the vedolizumab extended access program who had their dosing interval changed from 4to 8-weekly.1 At baseline, 93.1% were in clinical remission after a mean of 6.6 years on vedolizumab. Most (71.1%) were anti-tumour necrosis factor (anti-TNF)-naive. Only a few had a flare, hospitalisation or corticosteroids in the preceding 12 months. At 2 years, 93.9% of ulcerative colitis (UC) and 91.6% of Crohn's disease (CD) patients remained on 8-weekly dosing. Only 6.1% and 8.4% of UC and CD patients reverted to 4-weekly dosing; relapse was reported in 9.1% and 14.0% of UC and CD patients, respectively. There were no new safety concerns. These findings suggest that 8-weekly dosing (more commonly utilised in clinical practice) maintained clinical effectiveness with high persistence rates. The study findings, though interesting, are unsurprising. First, there were no meaningful differences in clinical outcomes between 4or 8-weekly vedolizumab in the registration clinical trials suggesting that 8-weekly dosing may suffice during maintenance therapy. Furthermore, there is no clear exposure-efficacy relationship for vedolizumab during the maintenance phase, either in clinical trials or subsequent cohort studies.2,3 This, in part, may relate to near complete occupancy of α4β7 integrin in peripheral blood memory T cells regardless of dose, drug levels or clinical response, suggesting that dose escalation may not necessarily achieve superior outcomes (or vice versa with dose reduction).4 This is in keeping with previously published data from the same cohort that showed that vedolizumab trough levels decreased following dose reduction, but C-reactive protein and clinical remission rates did not.5 Notably, however, the findings by Danese et al do not necessarily imply that 4-weekly dosing is redundant in clinical practice. Dose intensification in patients failing vedolizumab therapy recaptures clinical response as shown in meta-analysis and observational cohort studies.6-8 Mechanisms for the observed efficacy of dose intensification are unclear and may relate to emerging evidence of vedolizumab's effects extending beyond the inhibition of gut T-cell trafficking to B cells, and macrophages, for example.4 Further data are needed to identify de-escalation strategies for vedolizumab to inform clinical practice as current evidence is limited. A previously published vedolizumab dose-lengthening study from a subset (n = 34) of patients from the GEMINI study showed a low relapse rate (15%, median follow-up 43 weeks).9 In a multi-centre cohort study, vedolizumab withdrawal in 98 IBD patients in steroid-free remission resulted in relapse-free survival of 59% at 1 year.10 The extended follow-up in Danese et al's study further adds to the evidence in this area. The study lacks critical information on biomarker status and endoscopic activity prior to de-escalation, which needs to be addressed in future well designed, prospective studies. For now, the findings impart further confidence in the long-term favourable safety profile of vedolizumab and that dose reduction to 8-weekly is a sound strategy for patients in clinical remission.