. Author manuscript; available in PMC: 2020 Apr 27.

Published in final edited form as: Lancet. 2019 Mar 29;393(10182):1708–1720. doi: 10.1016/S0140-6736(18)32592-3

Table 2.

Multivariable Logistic Regression Models of Week 52 CS-free Remission in All Patients

	All patients (N=386^a)	Patients with biological data (N=177)
	Clinical Model	Clinical Model^b	Clinical + Biological Model
Number of events (%)	147 (38%)	69 (39%)	69 (39%)
Baseline predictors:	Odds Ratio (95% CI) p-value	Odds Ratio (95% CI) p-value	Odds Ratio (95% CI) p-value
PUCAI <45^c	1.84 (1.18, 2.89) 0.008
Hemoglobin ≥10 g/dL (w/o Wk 4 remission^d)	4.24 (1.46, 12.31) 0.008	6.79 (1.45, 31.76) 0.015	5.72 (1.16, 28.23) 0.032
Week 4 Remission^e	9.50 (3.39, 26.63) <0.0001	15.11 (3.39, 67.44) 0.00037	14.92 (3.18, 69.98) 0.00061
Antimicrobial Peptide Gene Signature			0.57 (0.39, 0.81) 0.0022
Ruminococcaceae (560535) OTU log relative abundance^f			1.43 (1.02, 2.00) 0.036
Sutterella (589923) OTU log relative abundance^f			0.81 (0.65, 1.00) 0.049
Model Characteristics
AUC (95% CI)	0.70 (0.65, 0.75)	0.68 (0.61, 0.75)	0.75 (0.68, 0.83)
CV AUC (95% CI)	0.63 (0.57, 0.69)	0.49 (0.40, 0.58)	0.72 (0.64, 0.80)
R²	0.16	0.17	0.29
Sensitivity (95% CI)	47% (39%, 55%)	70% (57%, 80%)	49% (38%, 61%)
Specificity (95% CI)	77% (71%, 82%)	60% (50%, 69%)	78% (70%, 85%)
PPV (95% CI)	56% (47%, 64%)	53% (42%, 63%)	58% (46%, 71%)
NPV (95% CI)	70% (65%, 76%)	76% (65%, 84%)	71% (62%, 79%)
P-values for Clinical+Biological vs. Clinical Model^g:
Likelihood Ratio Test			0.00037
Comparison of AUC			0.014
Hosmer-Lemeshow Goodness of Fit test median MI p-value (% of imputations with p > 0.05)	P = 0.42 (100%)	P = 0.99 (100%)	P=0.25 (100%)

Week 52 CS-free remission was defined as PUCAI < 10 and no corticosteroids (CS) for 28 days without additional therapy or colectomy.

CV AUC = AUC from leave-one-out cross-validation, PPV=positive predictive value, NPV = negative predictive value

Note: Missing covariate data imputed via multiple imputation. Clinical parameters selected by LASSO. Sensitivity, specificity, PPV, and NPV were based on a predicted probability of 0.50.

The evaluable population excludes participants who discontinued the study without additional therapy or colectomy and without protocol violations.

The clinical model was run on the subset of participants with biological data. Clinical model factors with p > 0.05 in this smaller cohort were removed from the model.

PUCAI < 45, irrespective of initial treatment.

The interaction of hemoglobin ≥10 g/dL and Week 4 Remission was statistically significant (p=0.042) and the combinations of hemoglobin ≥ 10 and week 4 remission were combined into a 3-level variable: 1) neither hemoglobin≥10 and no week 4 remission, 2) hemoglobin≥10 and no week 4 remission, and 3) week 4 remission regardless of hemoglobin. Patients with low hemoglobin not achieving week 4 remission had a very low rate of week 52 cs-free remission, while those reaching week 4 remission had the same chance of week 52 cs-free remission as those who started with higher hemoglobin.

Week 4 remission: PUCAI < 10 at week 4 with no prior treatment escalation or colectomy

Log relative abundance was calculated by taking the log base 10 of the OTU plus half of the minimum value

Compares the clinical model in the subset of patients with biological data against the clinical + biological model

The predicted probability of CS-free remission for someone with PUCAI<45, hemoglobin ≥10 and week 4 remission = exp(−2.449 + 0.612*1 + 1.443*0 + 2.252*1)/(1+ exp(−2.449 + 0.612*1 + 1.443*0 + 2.252*1)) = 0.60; see supplemental Table S6A.