. 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 3.

Multivariable Logistic Regression Models of Escalation to Anti-TNFα by Week 52 for Moderate/Severe Patients

	Moderate/severe patients (N=232^a)	Moderate/severe Patients with biological data (N=118^b)
	Clinical Model	Clinical Model	Clinical + Biological Model
Number of events (%)	94 (41%)	46 (39%)	46 (39%)
Baseline predictors:	Odds Ratio (95% CI) p-value	Odds Ratio (95% CI) p-value	Odds Ratio (95% CI) p-value
Total Mayo score ≥11	4.38 (2.25, 8.54) 0.0002
Rectal biopsy eosinophil peak count > 32/hpf	0.48 (0.25, 0.92) 0.027
Higher 25 (OH) D per increase in category: 1 = < 20 ng/mL 2 = 20– < 30 ng/mL 3 = ≥ 30 ng/mL	0.60 (0.37, 0.96) 0.034	0.29 (0.11, 0.74) 0.010	0.31 (0.14, 0.71) 0.0052
Hemoglobin ≥10 g/dL	0.50 (0.26, 0.95) 0.033	0.39 (0.20, 0.76) 0.0063	0.33 (0.11, 0.94) 0.038
Week 4 Remission^c	0.36 (0.19, 0.68) 0.0015	0.16 (0.06, 0.41) 0.00012	0.21 (0.07, 0.58) 0.0029
Transport and Antimicrobial Gene Signature			0.31 (0.16, 0.61) 0.00063
Oscillospira (581079) OTU log relative abundance^d			0.64 (0.44, 0.92) 0.018
Model Characteristics
AUC (95% CI)	0.78 (0.72, 0.84)	0.80 (0.72, 0.88)	0.88 (0.81, 0.94)
CV AUC (95% CI)	0.75 (0.68, 0.82)	0.75 (0.65, 0.84)	0.84 (0.76, 0.91)
R²	0.32	0.37	0.52
Sensitivity (95% CI)	58% (47%, 68%)	63% (49%, 77%)	66% (52%, 80%)
Specificity (95% CI)	85% (78%, 92%)	82% (73%, 91%)	83% (74%, 91%)
PPV (95% CI)	73% (61%, 84%)	69% (55%, 83%)	71% (57%, 85%)
NPV (95% CI)	75% (68%, 82%)	78% (68%, 87%)	79% (70%, 89%)
P-values for Clinical+Biological vs. Clinical Model^e:
Likelihood Ratio Test			0.00004
Comparison of AUC			0.016
Hosmer-Lemeshow Goodness of Fit test median MI p-value (% of imputations with p > 0.05)	P = 0.43 (99%)	P=0.96 (100%)	P=0.53 (100%)

Moderate/Severe = initiated on IV CS or oral CS with PUCAI ≥ 45. CV AUC = AUC from leave-one-out cross-validation, PPV = positive predictive value, NPV = negative predictive value.

Note: Missing clinical covariate data imputed via multiple imputation. Clinical parameters selected by LASSO. Sensitivity, specificity, PPV, and NPV are based on a predicted probability of 0.5.

Note: Escalation to anti-TNFα includes one patient starting a calcineurin inhibitor and one patient who received colectomy without escalation to anti-TNFα.

The evaluable population excludes participants who discontinued the study without additional therapy or colectomy and with no protocol violations.

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

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 Escalation to Anti-TNFα for someone with mayo ≥11, eos < 32, vitamin D < 20, hemoglobin <10, and no week 4 remission = exp(1.587 + 1.477*1 – 0.738*0 – 0.514*0 – 0.694*0 – 1.014*0) / (1+ exp(1.587 + 1.477*1 – 0.738*0 – 0.514*0 – 0.694*0 – 1.014*0)) = 0.96; see supplemental Table S8A.