Ustekinumab for Perianal Crohn's Disease: The BioLAP Multicenter Study From the GETAID

Abstract

INTRODUCTION: New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti–tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort. METHODS: We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method. RESULTS: Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96–7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15–1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively. DISCUSSION: Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.

Comparison of short‐ and long‐term effectiveness between ustekinumab and vedolizumab in patients with Crohn's disease refractory to anti‐tumour necrosis factor therapy

“…We did not find any difference between the two treatments on the rate of healing of perianal lesions, although recent data suggested more promising results for ustekinumab in patients with perianal lesions 28 than for vedolizumab 29 . In addition, both drugs were very safe in our cohort with no difference between the two drugs as previously widely reported 8‐10 …”

How to Optimize Treatment With Ustekinumab in Inflammatory Bowel Disease: Lessons Learned From Clinical Trials and Real-World Data

“…In this cohort, no predictive factors were associated with the main outcomes, and only the number of prior anti-TNF agents (≥3 drugs) showed a trend toward a reduced response rate. No additional predictive factors have been associated with fistula response or healing in real-world experience reported so far (23,24,38,64,65).…”

“…Data from uncontrolled real-world studies have reported heterogeneous results on fistula response and closure rates (23,24,64,65). In 148 patients with active perianal disease included in a observational cohort from the GETAID, 39% achieved treatment success with UST (64). In this cohort, no predictive factors were associated with the main outcomes, and only the number of prior anti-TNF agents (≥3 drugs) showed a trend toward a reduced response rate.…”

“…However, this analysis included data only up to December 2016, so information from more recent cohorts may include additional and has the potential to obtain different conclusions. Data from uncontrolled real-world studies have reported heterogeneous results on fistula response and closure rates (23,24,64,65). In 148 patients with active perianal disease included in a observational cohort from the GETAID, 39% achieved treatment success with UST (64).…”

Editorial: is hyperbaric oxygen a therapeutic opportunity for refractory perianal Crohn's disease?

“…Existing first‐line therapies (mainly, tumour necrosis factor [TNF] antagonists) are only moderately effective in achieving long‐term fistula healing, even when used optimally 1,2 . Furthermore, the second generation biologic agents vedolizumab and ustekinumab appear to have only marginal benefit when used as salvage therapies 3,4 . Although promising, mesenchymal stem cell therapy is not yet widely available 5 .…”