Although an absence of rectal bleeding (to identify endoscopic remission) was found in adult patients with mild to moderate ulcerative colitis (UC) treated with mesalazine, many individuals in remission still had increased stool frequency, which indicates that it may not be a sensitive marker of disease activity in this population, according to a study published in Clinical Gastroenterology and Hepatology.
The association between rectal bleeding and increased stool frequency with endoscopic findings in patients with mild to moderate UC remains unclear. To evaluate the association, investigators performed a post-hoc analysis of data from a phase 3 non-inferiority trial of adults with mild to moderate UC (N=817) who were treated with mesalazine. The researchers obtained data on rectal bleeding, stool frequency, and Mayo endoscopic subscores (MESs) at weeks 0, 8, and 38, and evaluated the specificity, sensitivity, and positive and negative predictive value of rectal bleeding and stool frequency at weeks 8 and 38 to identify participants with MESs of 0 and/or 1. The Spearman’s rank correlation coefficient was used to quantify associations between changes in stool frequency and rectal bleeding and changes in MES after treatment. MES scores were available for 763 participants at week 8 and for 657 at week 38.
At week 8, 82 of 763 (10.7%) participants had MES scores of 0 and 310 of 763 (40.6%) had MES scores of 0/1. At week 38, 167 of 657 (25.4%) participants had MES scores of 0 and 363 of 657 (55.3%) had MES scores of 0/1. At week 8, 7 of 82 (8.5%) of participants with an MES of 0 had a rectal bleeding score of ≥1 and 40 of 82 (48.8%) had a stool frequency score of >1. At week 38, 6 of 167 (3.6%) participants had a rectal bleeding score of ≥1 and 63 of 167 (38%) had a stool frequency score of ≥1. Among patients with MESs of 0 or 1, 50 of 310 (16.1%) participants had a rectal bleeding score of ≥1 and 162 of 310 (52.3%) had had a stool frequency score of ≥1 at week 8; at week 38, 18 of 363 (5.0%) participants had a rectal bleeding score of ≥1 and 141 of 363 (38.8%) had a stool frequency score of ≥1.
The Spearman rank correlation coefficients for change in rectal bleeding with change in MES at week 8 were 0.39 (95% CI, 0.32-0.45; P <.001) compared with 0.34 (95% CI, 0.27-0.40; P <.001) for stool frequency. Among 389 participants with improved MES scores compared to baseline, 90.0% (350 of 389) had improved rectal bleeding and 79.2% (308 of 389) had improved stool frequency. Over half of participants with no change or worsening MES scores experienced improvement in stool frequency (51.1%, 191 of 374) or rectal bleeding (55.6%, 208 of 374).
Study investigators concluded, “While the absence of RB or SF is associated with endoscopic remission, a substantial proportion of patients will continue to have residual increased SF despite achieving a MES of 0 or 1, particularly during induction. In patients with persistent symptoms, fecal calprotectin is a sensitive marker for endoscopic remission although specificity is limited. Therefore, it may play an adjunctive role in triaging patients who are most likely to benefit from endoscopy. Overall, our findings highlight the limitations of using PROs alone for assessment of treatment response and the importance of objective endoscopic evaluation even in patients with mild-to-moderate UC.”
Disclosure: This clinical trial was supported by Tillotts Pharma, AG. Please see the original reference for a full list of authors’ disclosures.
Ma C, Sandborn WJ, D’Haens GR, et al. Discordance between patient-reported outcomes and mucosal inflammation in patients with mild to moderate ulcerative colitis [published online September 20, 2019]. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.09.021