Area Editoriale
Background & Aims: Clinical remission, defined by a composite of patient reported outcomes and Mayo endoscopy subscore (MES) 0 or 1 is a recommended treatment target in patients with ulcerative colitis (UC). We estimated whether incorporating more rigorous remission definitions, of endoscopic remission (MES 0) and histologic remission, affects risk of relapse.
Methods: Through a systematic review, we identified cohort studies in adults with UC in clinical remission that reported a minimum 12-month risk of clinical relapse, based on MES (0 vs 1) and/or histologic disease activity, in patients with endoscopic remission. Using random effects meta-analysis, we calculated relative and absolute risk of clinical relapse in patients with UC achieving different treatment targets.
Results: In a meta-analysis of 17 studies that included 2608 patients with UC in clinical remission, compared to patients achieving MES 1, patients achieving MES 0 had a 52% lower risk of clinical relapse (relative risk, 0.48; 95% CI, 0.37–0.62). The median 12-month risk of clinical relapse in patients with MES 1 was 28.7%; the estimated annual risk of clinical relapse in patients with MES 0 was 13.7% (95% CI, 10.6–17.9). In a meta-analysis of 10 studies in patients in endoscopic remission (MES 0), patients who achieved histologic remission had a 63% lower risk of clinical relapse vs patients with persistent histologic activity (relative risk, 0.37; 95% CI, 0.24–0.56). Estimated annual risk of clinical relapse in who achieved achieving histologic remission was 5.0% (95% CI, 3.3–7.7).
Discussions and conclusions: The findings of this study are consistent with previous observations that histologic remission may be the treatment target that conveys the best long-term prognosis. The ability of current therapies to achieve more stringent endpoints, however, needs to be better evaluated before incorporating these endpoints in the treat-to-target paradigm. Whether proactively trying to achieve these endpoints with treatment optimization under the treat-to-target paradigm will result in similar benefits is unknown; furthermore there will be interest in any potential safety implications of treatment escalation in order to achieve more stringent targets. Authors were unable to separately ascertain the potential benefit of achieving these rigorous targets on outcomes such as hospitalization, colectomy and colorectal cancer, as well as potential harms in a quest to achieve more rigorous endoscopic and histologic remission definitions
In conclusion, in a systematic review and meta-analysis of patients with UC in clinical remission, patients with UC achieving treatment end points of endoscopic AND/OR histologic remission have a substantially lower risk of clinical relapse as compared to patients achieving conventionally-defined clinical remission, with the lowest risk of relapse in patients who achieve combined endoscopic and histologic remission. These end points may be considered as preferred treatment targets, but future studies are needed to evaluate the population-level feasibility and cost-effectiveness of treating patients with UC to these end points.