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Combined Histologic and Endoscopic Improvement Does Not Increase Prognostic Benefit Over Endoscopic Improvement Alone in Ulcerative Colitis

Marietta Iacucci, MD, PhD, FASGE reviewing Wong ECL, et al. J Crohns Colitis 2023 Feb 23.

Symptomatic and endoscopic remission are recommended targets in ulcerative colitis (UC) because they are associated with better long-term favorable outcomes. Nevertheless, histologic activity may persist in up to 30% of patients, leading to an increased risk of clinical relapse, steroid use, surgery, and hospitalization. However, histologic remission/healing has yet to be a formal target because there is insufficient evidence regarding its benefit over endoscopic improvement (EI) alone. Thus, the role of combined histologic and endoscopic mucosal improvement (HEMI) has been proposed in clinical trials. The VARSITY trial compared vedolizumab and adalimumab in UC, and in the previous analysis, postinduction histologic improvement (HI; week 14) predicted a one-year outcome.

This post hoc analysis of the VARSITY trial evaluated the prognostic role of HEMI (Mayo endoscopic subscore ≤1 and Geboes score <3.2) compared to EI alone and considered clinical outcomes, patient-reported outcomes, and inflammatory markers of patients achieving postinduction (week 14) and postmaintenance HEMI (week 52). 

Of the 468 patients with one year of data, 166 (35.5%) achieved HEMI and 209 (44.7%) attained EI at postinduction. Patients who achieved HEMI at postinduction and at week 52 had lower disease activity, reduced rectal bleeding and stool frequency, and lower fecal calprotectin and C-reactive protein compared to patients with EI alone. However, there was no difference for achievement of clinical remission, corticosteroid-free remission, and treatment failure at one year.


Despite an association with lower disease activity at postinduction and one year, there is no additional value of HEMI over EI in predicting one-year outcomes. Similarly, the PICaSSO group showed that solely endoscopic remission defined by a virtual electronic chromoendoscopy score predicts specified clinical outcomes as well as HI and HEMI. However, large prospective studies with a longer follow-up and inclusion of more drug classes are needed to define the correct timing for eventual drug escalation/withdrawal.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.

Marietta Iacucci, MD, PhD, FASGE

Bio and Disclosures


Wong ECL, Dulai PS, Hasan B, Marshall JK, Reinisch W, Narula N. Combined histologic and endoscopic endpoints at post-induction lack additional prognostic value compared to endoscopic improvement alone in ulcerative colitis: a post-hoc analysis of the VARSITY study. J Crohns Colitis 2023 Feb 23. (Epub ahead of print) (