Ustekinumab is associated with superior treatment persistence but not with higher remission rates versus vedolizumab in patients with refractory Crohn’s disease: results from a multicentre cohort study

Abstract

Background: Treatment with antitumor necrosis factor alpha (anti-TNF-α) is safe and effective as first-line therapy; however, its efficacy is limited due to primary nonresponse (PNR) and secondary loss of response (LOR), resulting in treatment discontinuation in approximately 40%–50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapies could be good alternatives in patient with anti-TNF failure; however, no head-to-head randomized comparison of these drugs as second- or third-line treatments has been made. Objectives: This study aimed to assess the treatment persistence and comparative effectiveness of UST and VDZ in patients with refractory Crohn’s disease (CD). Design: In this nationwide retrospective study, patients with CD on UST or VDZ maintenance therapy were enrolled. Clinical data at baseline, after induction, and at week 52 were obtained. Methods: Clinical and biochemical activities as well as corticosteroid-free remission (SFR) rates were assessed, while concomitant medications, comorbidities, hospitalizations, and surgeries were recorded during the follow-up to detect any predictors. Results: A total of 161 UST- and 65 VDZ-treated patients completed the follow-up. No significant difference in clinical or biochemical remission rates was observed after induction between the two treatment groups; however, clinical remission rate at week 52 was higher in UST group. UST showed superior drug persistence than VDZ (86.5%, 57.9%, p < 0.0001). The drug type was predictive of clinical SFR at week 52 [ p = 0.011, odds ratio (OR) = 2.39 with UST]. Drug failure rates were higher for VDZ than those for UST (PNR rates: 21.54% and 4.97%, respectively, p < 0.001, OR = 8.267, p = 0.001). LOR and escalations were more common during UST treatment (61.5% versus 36.9%, p < 0.001; 64.2% versus 23.1%, p < 0.001). Hospital and surgical admission rates did not differ significantly. Only one adverse event occurred with VDZ at week 20, which led to drug cessation. Conclusions: VDZ and UST were safe and effective for treating patients with CD in whom anti-TNF therapy failed. UST showed superior drug persistence than VDZ, but dose escalation was more frequent. Biologicals used in lower treatment lines resulted in better drug persistence.

Meta‐analysis: Persistence of advanced therapies in the treatment of inflammatory bowel disease

“…Among the 63 publications, 10‐72 58 were journal articles and 5 were international conference abstracts. Two conference abstracts 71,72 were replaced by subsequent published articles found in our search.…”

Ustekinumab or Vedolizumab after Failure of Anti-TNF Agents in Crohn’s Disease: A Review of Comparative Effectiveness Studies

“…Garcia et al also showed higher clinical remission and steroid-free clinical remission in patients treated with ustekinumab after the induction period [19]. In the other two studies, though, patients treated with ustekinumab had numerically higher clinical or steroid-free remission rates that were not statistically significant after propensity adjustment [14,20]. Among the studies that reported the biochemical outcomes during induction (Table 3), only one reported a higher deep clinical remission (steroid-free clinical remission and faecal calprotectin < 100 µg/g) rate in patients treated with ustekinumab [14].…”

“…Eight studies reported ustekinumab was superior to vedolizumab in achieving clinical response and/or steroid-free clinical remission or treatment persistence (Table 2B) [7,8,11,12,14,17,18,20]. Four studies did not find any difference in outcome among both groups [9,10,13,19].…”

“…Among the studies that reported clinical outcomes at weeks 14-20 (induction period) (Table 2A), four studies showed superior clinical response, treatment persistence, and/or clinical steroid-free remission to be higher in patients treated with ustekinumab [8,14,18,20]. The sample size for these studies ranged from 130 to 835, and three of these studies adjusted for confounders using propensity weighting [9,11,19].…”

“…Three studies reported clinical outcomes of perianal disease treated with either ustekinumab or vedolizumab (Table 4) [14,20,22]. Two studies showed no significant difference between patients treated with ustekinumab and vedolizumab [14,20].…”