BACKGROUND
Prospective long-term data on vedolizumab (VDZ) in children with Crohn’s disease (CD) and ulcerative colitis (UC) are lacking. In this prospective, multicenter cohort study, we aimed to evaluate the effectiveness and safety of maintenance therapy with VDZ in pediatric patients with CD and UC.

METHODS
Children commenced on VDZ were followed at baseline and 2, 6, 14, 30 and 54 weeks thereafter. Serum for drug levels and stool for calprotectin were repeatedly obtained. The primary outcome was sustained steroid-free remission (SSFR), defined as clinical remission (PUCAI<10 or wPCDAI<12.5) without steroids or exclusive enteral nutrition at both 30 and 54 weeks, analyzed under the ITT principle.

RESULTS
139 children were enrolled (77 [55%] UC, 62 [45%] CD; age 14.9 years (IQR 12.0-16.6). Of the 119 (86%) children >30kg, 110 (92%) received a dose of 300mg; 20 (14%) weighed<30 kg and received a dose of 8.3mg/kg (IQR 7–10.3). Week-54 remission rate was 52% in UC and 37% in CD; SSFR rates were 42% and 24%, respectively (OR 2.2 [95%CI 1.1-4.7]; Figure 1). SSFR rate was numerically higher in isolated colonic CD than in ileal disease (5/11 [45%] vs 10/49 [20%], OR 3.3 [95%CI 0.8-12.9]; p=0.08). Infusion interval was shortened in 22 children (10 [13%] UC, 12 [19%] CD), of whom none achieved SSFR.

SSFR rate was higher in week-6 responders compared to non-responders in UC (51% vs 27%, OR 2.9 [1.1-7.7]) and CD (35% vs 14%, OR 3.4 [95%CI 0.95-12.4]), similar to the week-14 figures (UC: 50% vs 22%, OR 3.6 [1.2-11.1]; CD: 36% vs 8%, OR 6.2 [1.3-30.8]). SSFR was eventually achieved in 49% of UC children having mild disease at week 6 and 14% with moderate-severe disease (OR 5.8 [95%CI 1.2-28.2]); the corresponding rates in CD were 31% and 0% (p=0.02).

In multivariable models, the best predictors in CD were lower wPCDAI at baseline (AUROC 0.88 [95%CI 0.79-0.96]; optimal cutoff 25 (sens/spec 76%/80%)) and at week 6 (0.90 [0.82-0.98]; optimal cutoff 17.5 (80%/87%)). In UC, the best predictors were PUCAI at week 6 (0.70 [0.57-0.82]; optimal cutoff 10 (64%/57%)) and at week-14 (0.78 [0.67-0.89]; optimal cutoff 5 (76%/60%; Table 1).

In children <30kg, SSFR was associated with week 6 drug levels >30ug/mL, not reaching statistical significance (3/6 [50%] vs 1/8 [13%], OR 7.0 [95%CI 0.5-97]). By week 54, 197 adverse events were recorded, of which were VDZ-related in 8 (5.8%) children, and in 2 (1.4%) led to stopping VDZ; none were severe. There was 1 lymphoma case judged to be unrelated to VDZ.

CONCLUSION:
VDZ was effective for maintaining remission, more so in UC and in colonic CD. The likelihood of eventually achieving SSFR was very low in children with moderate-severe disease or those not showing response at week 6, particularly in CD.

Figure 1 - Clinical Outcomes at 6, 14, 30, and 54 Weeks for Crohn's Disease and Ulcerative Colitis

Table 1

Richard Russell

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