Relationship between endoscopic mucosal healing and histologic inflammation during remission maintenance phase in ulcerative colitis: a retrospective study

Kanazawa, Mimari; Takahashi, Fumiaki; Tominaga, Keiichi; Abe, Keiichiro; Izawa, Naoya; Fukushi, Koh; Nagashima, Kazunori; Kanamori, Akira; Takenaka, Kazuhiro; Sugaya, Takeshi; Iijima, Makoto; Takada, Atsuko; Imai, Yasuo; Hiraishi, Hideyuki; Irisawa, Atsushi

doi:10.1055/a-0869-7619

Cited by 24 publications

(17 citation statements)

References 34 publications

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“…We found that beyond degree of endoscopic healing, no conventional demographic or clinical factors could identify which patients treated‐to‐target of EH would achieve histologic remission. While prior studies have not evaluated factors associated with achieving histologic remission, they have not identified any systematic differences in patients who achieve histologic remission vs persistent histologic activity after achieving EH 2,3,5 . We show in this cohort that conventional baseline factors do not determine if patients are able to achieve histologic remission.…”

Section: Discussionmentioning

confidence: 55%

“…Clinical remission, a composite outcome defined by a (PRO, patient reported outcome) of resolution of rectal bleeding and near normalisation of stool frequency and endoscopic healing based on MES 0 or 1, is the recommended treatment target in patients with UC, based on recent guidelines 1 . Approximately 50%‐60% patients with EH achieve histologic remission, whereas others have persistent histological activity 2 . Histologic remission, regardless of clinical and endoscopic activity, may have superior long‐term outcomes, 3‐5 warranting its examination as a treatment target in patients with UC 6 .…”

Section: Introductionmentioning

confidence: 99%

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Predictors and outcomes of histological remission in ulcerative colitis treated to endoscopic healing

Jangi

Yoon

Dulai

et al. 2020

Aliment Pharmacol Ther

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Summary Background Clinical remission is the recommended treatment target in ulcerative colitis. The predictors and outcomes of achieving histologic remission within a treat‐to‐target paradigm are not well established. Aim To evaluate the predictors and outcomes of achieving histologic remission in patients with ulcerative colitis treated‐to‐target of endoscopic healing (modified Mayo endoscopy score 0 or 1). Methods We conducted a retrospective cohort study in adults with active ulcerative colitis (modified Mayo endoscopy score 2 or 3), whose treatment was iteratively optimised to achieve endoscopic healing. We identified predictors of achieving histologic remission, and outcomes (risk of symptomatic relapse, and ulcerative colitis‐related hospitalisation and/or surgery) of achieving histologic remission vs persistent histologic activity, using Cox proportional hazard analysis. Results Of the 411 patients with clinically active ulcerative colitis, 270 achieved endoscopic healing. Of the 270 patients, 55% simultaneously achieved histologic remission. Depth of endoscopic healing at final endoscopic assessment was the only independent determinant of histologic remission (modified Mayo endoscopy score 0 vs 1: odds ratio, 0.31 [95% confidence intervals, 0.18‐0.52]). Over 28 months, achieving histologic remission was associated with a lower risk of clinical relapse (1‐year cumulative risk: 18.7% vs 29.5%; adjusted hazard ratio, 0.56 [0.37‐0.85]), and lower risk of hospitalisation (hazard ratio, 0.44 [0.20‐0.94]). The incremental benefit of achieving histologic remission was observed only in patients achieving Mayo endoscopy score 1, but not Mayo endoscopy score 0. Conclusions In patients with active ulcerative colitis treated‐to‐target of endoscopic healing, 55% simultaneously achieved histologic remission. Histologic remission, particularly in patients achieving modified Mayo endoscopy score 1, was associated with favourable outcomes. Treating to a target of histologic remission over endoscopic healing requires prospective evaluation.

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Predictors and outcomes of histological remission in ulcerative colitis treated to endoscopic healing

Jangi

Yoon

Dulai

et al. 2020

Aliment Pharmacol Ther

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“…In clinical practice the finding of Mayo endoscopic subscore (MES) 0–1 is considered “endoscopic remission” [3]. Recent data, however, indicates that MES 1 is not completely normal with regards to inflammatory histological state [6]. This increases the risk of relapse [7] and later complications.…”

Section: Introductionmentioning

confidence: 99%

Head to head comparison of two commercial fecal calprotectin kits as predictor of Mayo endoscopic sub-score and mucosal TNF expression in ulcerative colitis

Goll¹,

Heitmann²,

Moe³

et al. 2019

PLoS ONE

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BackgroundFecal calprotectin is widely used to monitor disease activity in patients with inflammatory bowel disease. Multiple commercial kits exist, however, since the analyses are not standardized, these kits cannot be used interchangeably. We aimed to perform a technical evaluation of two kits (Calpro from Calprolab, Norway and Calprest from Eurospital, Italy) and perform a tuning for detection of clinically relevant disease states in ulcerative colitis.Materials and methodsFor tuning against different clinical states a total of 116 patients with ulcerative colitis were recruited (67 of which were part of an earlier publication). For the technical evaluation an additional series of 80 random samples from the hospital lab were included. Technical evaluation was done by correlation and limits of agreement analysis; cut-off levels were explored by ROC analysis against clinically relevant actual states.ResultsThe technical evaluation revealed good correlation between assays, however a non-linear difference was found: At values below 200 mg/kg, no significant bias was found; in the interval 200–1000 mg/kg the Calprest assay measured on average 30% lower than Calpro; and at higher values Calprest measured 60% higher values than Calpro. Both assays predicted Mayo endoscopic score (MES) 0 (cutoff 28: sensitivity 0.38; specificity 0.82 for Calprest; cutoff 28: sensitivity 0.50; specificity 0.77 for Calpro), and MES 2–3 (cutoff 148: sensitivity 0.72; specificity 0.80 for Calprest; cutoff 208: sensitivity 0.64; specificity 0.80 for Calpro), but did not predict normalization of mucosal TNF transcript per se. A combination of calprotectin and MES predicted mucosal TNF transcript values reasonably well (Calpro: sensitivity 0.85, specificity 0.58; Calprest: sensitivity 0.85, specificity 0.61).ConclusionThe Calpro and Calprest assays correlated well, but subtle differences were found, underlining the need for kit-specific cut-off values. Both kits were most precise in predicting active inflammation (MES 2–3), but less so for prediction of mucosal healing (MES 0) and normalization of mucosal TNF gene expression.

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“…Therefore, it is considered that the association of 5-ASAs with a MES of 0 (the finding that a MES of 0 may be used as an index for the dose reduction of 5-ASAs) is different from the results of the present study. Additionally, while it has been reported that there are differences between MES 0 and MES 1 in terms of remission maintenance rates and surgery rates 2,40–42 , we found that it is also important to not only perform an endoscopic mucosal assessment but also to confirm histological healing, in order to ensure remission maintenance 43 . As the research gap in UC treatment, we studied the clinical issue of IM withdrawal was possible or not in UC cases that achieved MH.…”

Section: Discussionmentioning

confidence: 65%

Endoscopic score vs blood cell indices for determining timing of immunomodulator withdrawal in quiescent ulcerative colitis

Takenaka

Tominaga

Kanazawa

et al. 2019

Sci Rep

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While immunomodulators (IMs) are used as key drugs in remission maintenance treatment for ulcerative colitis (UC), there has been no evidence to date for determining monitoring methods and drug withdrawal. Therefore, we examined if a decrease in white blood cell count (WBC) and an elevation in mean cell volume (MCV) could be used as optimization indices and if mucosal healing (MH) could be a rationale for determining the time of IM withdrawal. Subjects were 89 UC patients who were using IMs and for whom clinical remission had been maintained. Those with a Rachmilewitz Clinical Activity Index score of 4 or lower and those with a Mayo endoscopic subscore (MES) of 0 or 1 were defined as MH. The remission maintenance rates of the following comparative groups were examined: an IM continuation group and an IM withdrawal group; an IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and an IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower; an IM continuation group of patients for whom MH had been achieved and an IM continuation group of patients for whom MH had not been achieved; and an IM withdrawal group with a MES of 0 and an IM withdrawal group with a MES of 1. A significantly higher remission maintenance rate was observed in the IM continuation group compared to the withdrawal group (p < 0.01). No significant difference was observed between the IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and the IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower (p = 0.08). Higher remission maintenance rates were observed in the IM continuation group of patients for whom MH had been achieved compared to the IM continuation group of patients for whom MH had not been achieved (p = 0.03). No significant difference was observed between the IM withdrawal group with MES 0 and the IM withdrawal group with MES 1. (p = 0.48). This retrospective study showed that remission maintenance could be firmly obtained by continuing IM administration in case of endoscopic MH; however, MH was not an indicator of IM withdrawal.

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Relationship between endoscopic mucosal healing and histologic inflammation during remission maintenance phase in ulcerative colitis: a retrospective study

Cited by 24 publications

References 34 publications

Predictors and outcomes of histological remission in ulcerative colitis treated to endoscopic healing

Predictors and outcomes of histological remission in ulcerative colitis treated to endoscopic healing

Head to head comparison of two commercial fecal calprotectin kits as predictor of Mayo endoscopic sub-score and mucosal TNF expression in ulcerative colitis

Endoscopic score vs blood cell indices for determining timing of immunomodulator withdrawal in quiescent ulcerative colitis

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