A total of 195 patients treated with vedolizumab and 245 treated with anti-TNFα agents from the EVOLVE study met the current study inclusion criteria (Table 1). Most (195/440, 44.3%) patients had non-stricturing, non-penetrating disease with/without perianal disease, and ileal (136/440, 30.9%) or ileocolonic (148/440, 33.6%) location with/without upper gastrointestinal disease. At baseline, 160/440 (36.4%) had moderate CD and 62/440 (14.1%) had severe CD. A total of 44/440 (10.0%) patients had fistulae at their most recent assessment prior to receiving their index treatment, and 224/220 (50.9%) had ongoing disease exacerbation (defined as disease worsening of symptoms attributed to CD as noted in the medical record by clinician assessment) at index.

The prediction model for vedolizumab identified the following 11 characteristics as predictors of time to clinical remission: location of intestinal involvement (colonic, ileal, or both), type of CD behavior (stricturing, penetrating, or neither), prior non-biologic therapy, use of immune modulators at treatment initiation, steroid dependency (dependent or refractory), fistulae at the most recent assessment prior to index, having one or more pre-existing EIMs at index, exacerbations at treatment initiation, prior emergency department/emergency room (ED/ER) visits, prior hospitalizations, and prior healthcare provider visits/referrals other than routine visits (Table 2).

The prediction model for anti-TNFα identified only age as a predictor of time to clinical remission (Table 2). The models were cross-validated and showed an AUC of 0.62 for the vedolizumab model and an AUC of 0.62 for the anti-TNFα model.

In the full population of included patients, clinical remission rates at 12 and 24 months based on unadjusted Kaplan–Meier analyses were 60.9% and 75.7% in patients treated with vedolizumab and 56.1% and 68.8% in patients treated with anti-TNFα agents. Unadjusted median time to clinical remission (95% confidence interval [CI]) was 9.0 (7.2–11.0) months for patients treated with vedolizumab and 10.1 (7.6–12.7) months for patients treated with anti-TNFα agents (unadjusted log-rank P = 0.35). After propensity score adjustment, clinical remission rates at 12 and 24 months were 63.2% and 75.0% in patients treated with vedolizumab and 51.2% and 64.9% in patients treated with anti-TNFα agents. Adjusted median time to clinical remission (95% CI) was 7.8 (6.3–10.9) months for patients treated with vedolizumab and 11.1 (9.6–18.1) months for patients treated with anti-TNFα agents (weighted log-rank P < 0.05).

Differences in the rates of remission with vedolizumab relative to anti-TNFα agents in propensity score adjusted analyses within each of the studied subpopulations are shown in Fig. 1. Tables S3–7 (see ESM) show baseline characteristics after adjustment in each subpopulation. The weighted median time to clinical remission for patients treated with vedolizumab relative to anti-TNFα agents in the subpopulation of patients with the top 20% of effect scores was 4.0 months for vedolizumab vs 14.1 months for anti-TNFα agents (adjusted hazard ratio [HR] 3.3, 95% CI 1.9–5.8). Corresponding median times to remission for vedolizumab vs anti-TNFα agents and adjusted HR estimates in the top 40%, top 60%, and top 80% subpopulations were 4.8 vs 18.1 months (HR 2.0, 95% CI 1.3–2.9), 4.8 vs 12.7 months (HR 1.7, 95% CI 1.2–2.2), and 4.8 vs 11.7 months (HR 1.4, 95% CI 1.0–1.8), respectively.

Kaplan–Meier curves for adjusted time to clinical remission, by subpopulation. The red line shows the TNFα treatment group and the green line shows the vedolizumab treatment group. TNF tumor necrosis factor. *Statistically significant

In each subpopulation, clinical remission by 1 year after index treatment was achieved in the majority of patients treated with vedolizumab compared with approximately half of the patients treated with anti-TNFα agents (Fig. 2). In the top 20% subpopulation, the estimated proportions of vedolizumab- and anti-TNFα-treated patients who achieved clinical remission by 1 year were 91.5% and 47.2%, respectively; in the top 80% subpopulation, the proportions were 73.5% and 50.6%, respectively.

Proportion of patients achieving clinical remission by a 1 year and b 2 years in the vedolizumab and anti-TNFα treatment groups, by subpopulation. TNFα tumor necrosis factor alpha

Compared with the full sample of patients treated with vedolizumab, patients in the top 20% and 40% subpopulations treated with vedolizumab were older (mean ages of 58.9 years and 55.1 years for the subpopulations, respectively, vs 51.8 years for the full sample), more likely to have non-stricturing and non-penetrating disease behaviors (62.2% and 60.7%, respectively, vs 43.6%), less likely to have fistulae (0.0% and 0.0%, respectively, vs 3.6%), less likely to have ongoing exacerbation of disease at index (75.6% and 67.4%, respectively, vs 45.6%), more likely to have EIMs (37.8% and 28.1%, respectively, vs 17.9%), and less likely to have healthcare provider visit/referrals other than routine visits (22.2% and 36.0%, respectively vs 50.8%), or ED/ER visits (0.0% and 0.0%, respectively vs 7.7%) (Table 3).

Simplified rules for the top 40% (rule A), top 60% (rule B), and top 80% (rule C) subpopulations are summarized (Fig. 3 and Table 4).

Kaplan–Meier curves for adjusted time to clinical remission, by subpopulation. The red line shows the anti-TNFα treatment group and the green line shows the vedolizumab treatment group. ED/ER emergency department/emergency room, TNFα tumor necrosis factor alpha. aBased on prediction models, an effect score was estimated for each patient as the difference in the predicted 1-year rate of clinical remission associated with vedolizumab vs anti-TNFα treatment

Rule A for the top 40% subpopulation was based on the following criteria: patients (i) had an exacerbation ongoing at index; (ii) did not have ED/ER visits prior to index; and (iii) had pre-index disease behavior classified as other than stricturing with/without perianal disease. Patients meeting these three criteria made up 32% of the patients included in our EVOLVE analysis. Among these patients, median time to clinical remission was 6.7 months for vedolizumab-treated patients (n = 55) and 18.1 months for anti-TNFα-treated patients (n = 86) (unadjusted log-rank P < 0.001), and the adjusted HR of clinical remission for vedolizumab vs anti-TNFα was 2.9 (95% CI 1.7–5.0).

Rule B for the top 60% subpopulation differs with respect to one condition compared with rule A above. Patients identified by this rule (i) had an exacerbation ongoing at index; (ii) did not have ED/ER visits prior to index; and (iii) did not have fistulae at the most recent assessment prior to index. Among patients meeting rule B criteria, median time to clinical remission was 7.2 months for vedolizumab-treated patients (n = 81) and 14.1 months for anti-TNFα-treated patients (n = 99) (unadjusted log-rank P < 0.01), and the adjusted HR of clinical remission for vedolizumab vs anti-TNFα was 2.1 (95% CI 1.3–3.4).

Rule C for the top 80% subpopulation was based on the following criteria: (i) did not have ED/ER visits prior to index; and (ii) did not have fistulae at the most recent assessment prior to index. Patients meeting these criteria encompassed 81% of the patients with CD included in our EVOLVE analysis. Among these patients, median time to clinical remission was 8.5 months for vedolizumab-treated patients (n = 174) and 11.1 months for anti-TNFα-treated patients (n = 182) (unadjusted log-rank P < 0.05), and the adjusted HR of clinical remission for vedolizumab vs anti-TNFα was 1.7 (95% CI 1.2–2.3).