One-year outcomes with ustekinumab therapy in infliximab-refractory paediatric ulcerative colitis: a multicentre prospective study

Background The phase 3 (UNIFI) trial of ustekinumab (anti-interleukin 12/23) demonstrated efficacy even after prior biologic failure in adult ulcerative colitis (UC), but paediatric data are lacking. Aim To prospectively monitor efficacy and serum concentrations of ustekinumab given to children with UC refractory to other biologics. Methods Children with anti-TNF refractory UC initiating ustekinumab intravenously at sites of the Canadian Children IBD Network prior to 12/2019 are included. The primary endpoint was steroid-free clinical remission with subcutaneous ustekinumab at 52 weeks (Paediatric Ulcerative Colitis Activity Index <10, no steroids >= 4 weeks). Ustekinumab levels were measured after week 20. Endoscopic improvement was defined as Mayo endoscopic subscore <= 1, or faecal calprotectin (FCP) <250 mu g/g if not re-colonoscoped. Results At six sites between 01/2018 and 11/2019, 25 children (median [IQR] age 14.8 years [12.3-16.2], 72% female) with UC duration 2.3 years (1.1-4.2) received intravenous ustekinumab (median dose/kg of 6.4 [5.5-7.5] mg). All patients had failed prior infliximab therapy, and 12 (48%) also vedolizumab. Five patients discontinued ustekinumab after IV induction (four undergoing colectomy). On intent to treat basis, 44% achieved the primary endpoint of steroid-free remission at week 52, including nine (69%) of 13 who previously treated with anti-TNF only vs two (17%) of 12 who previously failed also by vedolizumab (P = 0.008). Seven of 11 remitters met the criteria for endoscopic improvement. The median (IQR) trough levels (mu g/mL) were greater with q4 vs q8 weekly dosing (8.7 [4.6-9.9] vs 3.8 [12.7-4.8]) P = 0.02, but greater exposure was not associated with a superior rate of clinical remission. No adverse events were associated with therapy. Conclusion Ustekinumab demonstrated efficacy in this paediatric cohort with otherwise treatment-refractory UC. Treatment failure was not due to inadequate drug exposure.

Automated summary

The study monitored the efficacy and drug concentration of ustekinumab in adolescent ulcerative colitis patients, with 44% achieving steroid-free remission at 52 weeks, and 1 in 7 meeting the criteria for endoscopic improvement.