Highlights from

ECCO 2019

European Crohn's and Colitis Organisation's 14th congress

Copenhagen 6-9 March 2019

Ustekinumab as maintenance therapy and with shortened interval

Ustekinumab was found to be safe and effective as maintenance therapy in ulcerative colitis and Crohn’s disease [1]. Both ustekinumab 90 mg every 8 weeks (q8w) and every 12 weeks (q12w) subcutaneous achieved clinical remission and maintained clinical response, and was effective in achieving endoscopic healing and corticosteroid-free remission among patients with moderate-to-severe ulcerative colitis who were in clinical response with a single IV dose of ustekinumab. The safety results in ulcerative colitis patients were consistent with the known safety profile of ustekinumab in Crohn’s disease.

These were the main results of the phase 3, double-blind, randomised withdrawal study UNIFI. Participants were 523 patients with moderate-to-severe active ulcerative colitis who failed conventional or biologic therapy (including anti-TNF and/or vedolizumab) and had clinical response 8 weeks after receiving a single IV ustekinumab induction dose. After 44 weeks, 43.8% and 38.4% of ustekinumab q8w and q12w patients, respectively, were in clinical remission vs 24% of patients in the placebo group (P<0.001 and P=0.002, respectively). Significantly greater proportions of ustekinumab q8w and q12w patients maintained clinical response through week 44 (68.0% and 71.0% vs 44.6%; P<0.001) and achieved endoscopic healing and corticosteroid-free clinical remission vs placebo patients. The proportions of patients with adverse events (AEs), serious AEs, infections, and serious infections in both ustekinumab groups were generally comparable with placebo (see Table).

Summary of key safety findings

** Patients who had clinical response to ustekinumab IV induction dose and were randomised to placebo subcutaneous on entry of this maintenance study.
AE, adverse event; NMSC, nonmelanoma skin cancer q8w, every 8 weeks; q12w, every 12 weeks.*

In the same UNIFI study, subjects with moderately to severely active ulcerative colitis receiving IV ustekinumab induction had higher rates of endoscopic healing, histological healing, and histo-endoscopic mucosal healing than those receiving placebo [2]. Approximately 10% of subjects who did not achieve clinical response 8 weeks after IV ustekinumab achieved histo-endoscopic mucosal healing following a second (subcutaneous) dose. Histological healing was associated with reductions in clinical and endoscopic disease activity as well as patient-reported symptoms.

Some Crohn’s disease patients will partially respond to ustekinumab or will experience a secondary loss of response. These patients might benefit from shortening the interval between injections from 90 mg q8w to q4w. In a retrospective, multicentre cohort study, this treatment optimisation resulted in two-thirds of patients recapturing response (n=50/76) [3]. Clinical response was observed in 57% (n=43/69) after a median of 2.1 months. Colonic location, inflammatory behaviour, and duration of ustekinumab therapy before optimisation were associated with clinical response. After a median follow-up of 8.2 months, 47% (n=36/76) were still treated with ustekinumab; 26% (n=20/76) were in steroid-free clinical remission. Among the 29 patients with colonoscopy during follow-up, 10 had mucosal healing. At the end of follow-up, 35% (n=27/76) were hospitalised, and 22% (n=17/76) underwent surgery.

Keywords: Crohn’s disease, ulcerative colitis, endoscopy

  1. Sandborn WJ, et al. ECCO 2019, OP37.
  2. Li K, et al. ECCO 2019, DOP71.
  3. Fumery M, et al. ECCO 2019, OP24.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.