Findings from cross-sectional and predictive analyses of patients with UC treated with upadacitinib revealed HEMR and HEMI are associated with positive long-term clinical outcomes.
Endoscopic mucosal improvement (HEMI) and histologic endoscopic mucosal remissions (HEMR) were associated with better long-term clinical outcomes in patients with ulcerative colitis (UC) treated with upadacitinib (Rinvoq), according to findings from a recent post hoc analysis.
“Although previous studies have shown improved clinical outcomes with mucosal healing, these studies have not examined long-term outcomes in terms of histologic remission. Our study evaluated a unique composite endpoint of endoscopic histologic remission,” wrote investigators.1 “To our knowledge, this is the first study that assesses the benefits of achieving mucosal healing based on this stringent endoscopic and histologic measure.”
An inflammatory bowel disease linked to inflammation of the digestive tract, previous research suggests endoscopic healing and achievement of endoscopic remission have been associated with positive outcomes in patients with UC. Histologic remission recently emerged as another indicator of healing, making it a desirable treatment goal for patients.2
A team of investigators led by Laurent Peyrin-Biroulet, MD, PhD, head of the inflammatory bowel disease unit at Nancy University Hospital in Vandoeuvre-les-Nancy, France, sought to evaluate the clinical relevance of HEMI and HEMR in patients with UC participating in U-ACHIEVE, the phase 3 maintenance trial of upadacitinib. In order to examine the relationship between HEMI and HEMR endpoints and the achievement of long-term clinical outcomes, investigators performed post hoc analyses of histologic, clinical, and patient-reported outcome data.1
Patients with clinical response after week 8 or 16 in the U-ACCOMPLISH and U-ACHIEVE induction studies who received 52-week upadacitinib maintenance treatment through the U-ACHIEVE maintenance study were included in the analysis. Per trial protocol, patients received a full colonoscopy at screening and additional endoscopies at weeks 8 and 52, during which biopsies were collected from the rectosigmoid colon for evaluation by central readers to perform histologic and endoscopic scoring.1
For the purpose of analysis, investigators defined HEMI as Mayo endoscopic score (MES) ≤ 1 and Geboes histologic score ≤ 3.1 and HEMR as MES = 0 and Geboes histologic score < 2.0. To assess the relative importance of both endpoints for achieving long-term clinical and patient-reported outcomes, investigators conducted cross-sectional and predictive analyses on patients who achieved HEMR, patients who achieved HEMI without HEMR, and patients who did not achieve HEMI. Investigators used logistic regression models adjusted for histologic score at baseline, maintenance treatment dosage, gender, disease extent, disease duration, and baseline age and weight to estimate odds ratios (ORs) with 95% confidence intervals (CIs).1
Upon analysis, both HEMR and HEMI were associated with better long-term clinical outcomes. Results from the cross-sectional analyses showed patients with HEMR were more likely to achieve all clinical and patient-reported outcomes at week 52 than those with HEMI alone. Predictive analyses also showed patients with HEMR and HEMI at weeks 8 and 16 had significantly greater odds of achieving clinical remission (adjusted odds ratio [aOR], 3.6; P = .001) and endoscopic remission (aOR, 3.9; P < .001) at week 52 than patients not achieving HEMI and HEMR. Investigators pointed out these odds were lower among patients achieving HEMI without HEMR (clinical remission aOR, 3.2; P < 0.001; endoscopic remission aOR, 2.4; P = 0.010).1
“Early HEMI and HEMR are independent predictors of later remission and improved quality of life. Data on achieving the endoscopic remission and histologic remission endpoints and their benefit on long-term outcomes in upadacitinib-treated patients support HEMI and HEMR as desirable treatment goals in UC,” concluded investigators.1