. 2021 Nov 26;10(23):5551. doi: 10.3390/jcm10235551

Table 3.

The selected current studies of clinical, biomarker, endoscopic, and histological targets in the treatment of patients with UC.

Study (Year)	Study Type and Population	Treatment Targets	Main Results and Outcomes
1. Clinical target
S. Restellini et al. (2019) [24]	Systematic review of 23 studies (n = 3320)	PROs vs. endoscopic activity	Composite clinical measures including rectal bleeding (RB) and stool frequency (SF) had moderate to strong correlations with endoscopic disease activity; absence of RB identified patients with an inactive disease with higher levels of sensitivity than normalization of SF
N. Narula et al. (2019) [25]	Meta-analysis of 5 studies (n = 2132)	PROs vs. endoscopic remission (MES 0–1)	Combined 2 items, RB and SF subscores of 0 (Se 36%, Sp 96%, pos-LR 8.4, neg-LR 0.66 for endoscopic remission); RB subscore of 0 (Se 81%, Sp 68%, pos-LR 2.5, negative LR 0.28); SF subscore of 0 (Se 40% Sp 93%, pos-LR 6.0, and neg-LR 0.64)
P.A. Golovics (2021) [26]	Prospective study (n = 171)	Clinical scores (PRO2, partial Mayo, SCCAI) vs. endoscopic scores (MES, UCEIS)	RB, SF subscore of 0, or PRO2 remission (RBS0 and SF ≤ 1), partial Mayo (≤2), and SCCAI (≤2.5) remission were similarly associated with MES ≤ 1 or UCEIS ≤ 3 scores in ROC analysis (AUC: 0.93–0.72)
2. Biochemical target
L. Hart et al. (2020) [37]	Prospective study (n = 185)	FC cutoff level vs. endoscopic and histologic activity	FC ≥ 170 μg/g predicts active endoscopic activity (MES 2–3 from MES 0–1) (Se 64%, Sp 74%), and FC ≥ 135 μg/g predicts active histological activity (Se 54%, Sp 69%)
X. Ye et al. (2021) [58]	Meta-analysis of 9 studies (n = 1039)	FC vs. histologic response and remission	Accuracy of FC for histological remission: Se, Sp, and AUC of 76%, 71%, and 79%, respectively; accuracy of FC for histological response: Se Sp, and AUC of 69%, 77%, and 80%, respectively.
P.S. Dulai (2020) [45]	Systemic review of 26 studies (n = 2886)	Combined FC cutoff level and PRO2 vs. endoscopic activity	PRO2 remission (RBS 0 + SFS 0/1) and FC ≤ 50μg/g may avoid endoscopy in 50% patients with a false-negative rate < 5% RBS 2/3 + SFS 2/3 and FC ≥ 250 μg/g may avoid endoscopy in approximately 50% of patients with false-positive rate < 5% RBS 0 but SFS 2/3 led to false-negative and false-positive rates consistently > 10%, and endoscopic evaluation may be warranted
J. Li et al. (2019) [47]	Meta-analysis of 14 studies (n = 1110)	FC cutoff level vs. clinical relapse	9 studies used FC cutoff ≥ 150 μg/g: Se71% and Sp 86%; 5 studies used FC cutoff < 150 μg/g: Se 79% and Sp 64% in predicting relapse; most of the studies had follow-up ≥ 12 months
3. Endoscopic target
M. Arai et al. (2016) [79]	Prospective study (n = 285) UC patients with clinical remission	UCEIS vs. MES vs. clinical relapse	UCEIS correlated with MES (r = 0.93). The recurrence rate was 5.0% for UCEIS = 0, 22.4% for UCEIS = 1, 27.0% for UCEIS = 2, 35.7% for UCEIS = 3, and 75.0% for UCEIS = 4–5 during follow-up of 48 months
P. Boal Carvalho et al. (2016) [73]	Retrospective UC with corticosteroid-free remission (n = 138)	MES 0 vs. MES 1 vs. clinical relapse	Clinical relapse more frequent in patients with MES 1 than MES 0 (27.3 vs. 11.5%, p = 0.022); MES 1 increased risk of relapse (OR 2.89, 95% CI 1.14–7.36, p = 0.026) during 12 months
M. Barreiro-de Acosta et al. (2016) [70]	Prospective UC (n = 187)	MES 0 vs. 1 vs. clinical relapse	The relapse rates in patients with Mayo scores 0 and 1 were 9.4% and 36.6%, respectively, during the first 6 months
S. Jangi et al. (2020) [93]	Retrospective UC patients (n = 270) with persistent EH (two serial endoscopies)	MES 0 vs. MES 1 vs. clinical relapse	1 year CR of relapse in patients with persistent EH was 11.5% and in patients with persistent histological remission was 9.5% (interval of EH evaluation: 16 months)
H. Yoon et al. (2020) [76]	Meta-analysis of 17 studies (n = 2608) UC patients in clinical remission	MES 1 vs. MES 0 vs. clinical relapse	MES 0: 52% lower risk of CR (RR 0.48; 95% CI, 0.37–0.62) The median 12-month risk of CR in patients with MES 1 was 28.7%; the estimated annual risk of CR in MES 0 was 13.7% (95% CI, 10.6–17.9)
4. Histological target
S. Park et al. (2016) [90]	Meta-analysis of 13 studies (n = 1360)	Histologic activity vs. clinical relapse	In patients with clinical and endoscopic remission, HR was associated with lower clinical relapse (CR), RR 0.48, 95% CI: 0.39–0.60 during follow-up of 12 months
R.K. Pai et al. (2020) [92]	Prospective study (n = 281)	Histologic activity (GS ≥ 2B.1) vs. need for corticosteroids	The histologic activity was associated with systemic corticosteroid use (OR 6.34; 95% CI, 2.20–18.28; p = 0.001); mucosal neutrophils had higher rates of corticosteroid use (p < 0.001) during follow-up of 3 years
K.C. Cushing (2020) [76]	Prospective study (n = 83) UC patients with MES 0	Complete histologic normalization (Geboes score = 0) vs. relapse	Patients with complete histologic normalizations were less likely to have relapse compared to those without normalization (12% vs. 50%, p < 0.001) (OR 7.22, 95% CI 2.48–24.70) during follow-up of 2 years
B. Christensen et al. (2020) [101]	Retrospective study (n = 646) UC patients	Segmental vs. complete colon histological normalization vs. clinical relapse	Complete histological normalization of the bowel was associated with improved relapse-free survival (HR 0.23; 95% CI 0.08–0.68; p = 0.008); segmental normalization did not improve clinical outcomes
A. Gupta et al. (2020) [100]	Meta-analysis of 28 studies (n = 2677) UC patient with MES 0–1.	Histologic activity vs. clinical relapse	Histologically active increased risk of relapse (OR 2.41, 95% CI 1.91–3.04), basal plasmacytosis (OR 1.94), neutrophilic infiltrations (OR 2.30), mucin depletion (OR 2.05), and crypt architectural irregularities (OR 2.22) during follow-up of 12–72 months
H. Yoon et al. (2020) [76]	Meta-analysis of 10 studies, UC patients with MES 0	Histologic activity vs. clinical relapse	HR had a 63% lower risk of relapse vs. patients with persistent histologic activity (RR, 0.37; 95% CI, 0.24–0.56); the estimated annual risk of clinical relapse in HR was 5.0% (95% CI, 3.3–7.7%)