Vedolizumab vs. ustekinumab as second-line therapy in Crohn’s disease in clinical practice

Abstract

Background: Vedolizumab (VDZ) and ustekinumab (UST) have become available for the treatment of Crohn's dis ease (CD), however, due to limited clinical experience, the optimal treatment strategy after a failure of anti-tumor necrosis factor (anti-TNF) has yet to be elucidated. In our study, we aim to evaluate the ef ciency and safety of VDZ and UST as second-line clas ses of bio logical ther apy in a headto-head man ner in comparable populations of CD patients. Methods: Consecutive patients with CD who have previously been treated with anti-TNF ther apy were included. Patients were fol lowed at regular intervals coincident with drug applications and clinical activity (HBI-Harvey-Bradshaw Index), inflam matory markers (C-reactive protein, fecal calprotectin) and adverse events were recorded. The primary outcome was the proportion of patients in clinical remis sion in weeks 30-32 (HBI ≤ 4), the clinical response in terms of HBI decrease, and the withdrawal rate. Results: Forty-five patients with VDZ and 50 with UST were included. Both groups were comparable in all the evaluated parameters with the exception of the male-to-female ratio and the proportion of patients with penetrat ing dis ease phenotype. The proportion of patients in clinical remis sion increased from 44.4% at baseline to 58.1% in weeks 30-32 in the VDZ group and from 55.1% to 63.2% in the UST group; however, the increase was not statistical ly significant. The mean paired HBI dif erence between weeks 30-32 and baseline reached-1.94 ± 5.14 (p = 0.05) in the VDZ cohort and-2.94 ± 5.91 (p = 0.01) in the UST cohort. The proportion of patients in steroid-free clinical remis sion increased from 38.8% to 62.5% in the UST cohort (p = 0.04), and from 33.3% to 45.2% in the VDZ (p = 0.67). Six patients on VDZ and none on UST discontinued the treatment. Conclusion: Our study demonstrated a comparable ef cacy of VDZ and UST with respect to the rate of clinical remis sion and bio marker response; however, the steroid-spar ing ef ect of UST was more prominent. There is a need for prospective randomized head-to-head trials to as sess the optimal position of new bio logical agents in the treatment of patients with CD.

Systematic review with meta‐analysis: the effectiveness of either ustekinumab or vedolizumab in patients with Crohn's disease refractory to anti‐tumour necrosis factor

“…Among them, 32 were excluded for the following reasons: one was conducted in patients who had already received ustekinumab or vedolizumab, one focused on the dermatological effects of these drugs, three assessed the safety of ustekinumab and vedolizumab, two were literature reviews focused on these two drugs but did not include efficacy comparisons, ten were cost-effectiveness studies, ten were indirect comparisons including six network meta-analyses, two were studies including populations already included in other studies, three included anti-TNF naïve and exposed patients. Finally, six studies 18,19,20,21,22,24 were included for qualitative synthesis and quantitative meta-analysis. One study did not present adjusted results, and was not included in the main analysis but only in the sensitivity analysis.…”

“…We chose not to include one study comparing ustekinumab and vedolizumab at the end of induction in CD because it was based on unadjusted analyses 21 . Indeed, the choice of one or other of these two drugs can be biased by disease severity.…”

“…14 We chose not to include one study comparing ustekinumab and vedolizumab at the end of induction in CD because it was based on unadjusted analyses. 21 Indeed, the choice of one or other of these two drugs can be biased by disease severity. We nevertheless performed a sensitivity analysis at week 14 and the findings were similar to those of the main analysis.…”

“…The following studies were excluded: reviews of the literature, indirect treatment comparisons and network meta‐analyses; studies in patients who had already received either ustekinumab or vedolizumab, or in anti‐TNF naïve patients; safety comparisons of these treatments or any comparison other than intestinal efficacy; and cost‐effectiveness studies. Studies with unadjusted results were also excluded due to the presence of uncontrolled confusion bias, 21 however, they were included in a sensitivity analysis.…”

“…Indirect comparisons and network meta‐analyses of randomised trials have led to conflicting conclusions 11‐17 . Recently, several observational studies have compared ustekinumab and vedolizumab, in patients with CD 18‐24 …”