Discussion
UC
REGRESSION, INFILTRATE, DISEASE, REMISSION, MUCOSAL INFLAMMATION
In this post hoc analysis of patients with UC treated with upadacitinib, we observed that both HEMR and HEMI were associated with better long-term clinical outcomes. Achievement of HEMR at Week 8/16 was associated with numerically greater odds of improved clinical and patient-reported outcomes at Week 52 compared with patients who achieved HEMI without HEMR. Also, no UC-related hospitalizations and surgeries were observed during the 52-week maintenance phase in patients who achieved HEMR at Week 8/16.Results obtained in the present analysis support the long-term benefits to patients who achieve the stringent endpoint of HEMI. The HEMI endpoint combines both endoscopic and histologic improvement cutoffs (MES of 0 or 1 and Geboes histologic score ≤ 3.1, respectively). Patients who achieve the HEMI endpoint gained improvement in the macroscopic appearance of the mucosal surface as well as improvement in the microscopic and cellular features that are characteristic of mucosal inflammation [Results reported in this study also support previous evidence showing improved outcomes with an even stricter definition of mucosal healing. The HEMR endpoint (deep mucosal healing) combines both endoscopic and histologic remission cutoffs (MES = 0 and Geboes histologic score < 2.0, respectively) and requires that the mucosa appear normal upon endoscopic inspection, and that no acute inflammatory infiltrate (i.e., neutrophils and/or eosinophils) be present in either the crypts or lamina propria [Strengths of this study include patients’ receiving standard treatment and follow-up, as well as centralized histologic assessments as defined in the clinical trial protocol. 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, which was defined as Mayo endoscopic score = 0 and Geboes histologic score < 2.0. To our knowledge, this is the first study that assesses the benefits of achieving mucosal healing based on this stringent endoscopic and histologic measure. We acknowledge a number of limitations in our study. One limitation of this study is that logistic regression analyses were not performed on hospitalizations and surgeries because of the limited number of patients who were hospitalized or had surgery in the upadacitinib data. While this study used data from a randomized clinical trial, residual confounding may still arise from factors not included as covariates in the logistic regression. In addition, although full colonoscopy was performed for all participants at screening, the biopsy specimen was taken only from the rectosigmoid region and it is possible that a more proximal segment may, in some cases, have a greater histologic disease burden than the rectosigmoid regions. Furthermore, our results are based on data from Phase 3 clinical trials, which may not correspond to outcomes observed in routine clinical practice. Finally, outcomes in the maintenance study were assessed after a relatively short period of time (at Week 52). However, additional data is currently being collected in an ongoing long-term extension study, which will allow analysis of outcomes for a longer period of time.