Review article: predictors of response to vedolizumab and ustekinumab in inflammatory bowel disease

Abstract

integrin for vedolizumab and interleukin-12/23 pathways for ustekinumab) than the primary biological class, anti-tumour necrosis factor alpha (anti-TNF) agents. As the armamentarium for IBD increases in coming years, it will become important to understand factors associated with response in order to best position and personalise therapy.Aim: To summarise the current data on predictors of response to vedolizumab and ustekinumab in IBD patients. Methods:We conducted a comprehensive literature review. A PubMed search was performed using pre-defined key words and terms to identify relevant studies on predictors of response.Results: Patients with severe disease (by clinical activity and inflammatory biomarkers), or prior anti-TNF exposure are less likely to respond to vedolizumab. Ileocolonic disease, no prior surgery and uncomplicated phenotype were associated with better responses to ustekinumab in CD. Initial response seems to predict a better long-term maintenance in both therapies (P < 0.001). Contrary to anti-TNF therapies, immunogenicity appears to play less of a role in response. Conclusion:As the number of new biological therapies increase in IBD, identifying patients who are most likely to benefit from specific agents is of paramount importance to help best position IBD therapies.

Vedolizumab for perianal Crohn’s disease: a multicentre cohort study in 151 patients

“…Patients with prior exposure to three or more biologic agents were less likely to achieve success than less exposed patients, indicating the negative impact of refractory disease on vedolizumab therapy. Similarly, in other studies exploring predictors of response to vedolizumab, response rates were better in patients naive of biological agents …”

“…Addition of an immunomodulator at initiation was not a predictor of success in our cohort. It was not neither in the phase III trial, nor in the majority of retrospective studies . Immunogenicity rates appear to be very low with vedolizumab, so therapeutic response is less likely to be influenced by immunogenicity, contrary to what was described with anti‐TNF agents .…”

Real‐world short‐term effectiveness of ustekinumab in 305 patients with Crohn’s disease: results from the ENEIDA registry

“…However, there are no published data on potential predictors of a response to the new drugs used in CD. Barré et al recently published a review of various observational studies that analysed a response to SC ustekinumab in patients with CD . The predictors of response that have been most commonly associated with SC ustekinumab are immunomodulators, pattern and location of the disease and clinical severity (HBI) …”

“…Those whose anti‐TNFα was withdrawn owing to intolerance or AEs responded better to treatment, as was the case with the switch to a second anti‐TNFα agent in CD . Therefore, it seems that previous exposure to anti‐TNFα agents is a constant factor for response to the drugs used in CD (anti‐TNFα, vedolizumab and ustekinumab), with a greater response always observed in patients who are naïve to biologics . A possible explanation of this effect could be a greater severity of the disease or changes in the immunity after anti‐TNF exposure.…”

Subcutaneous rather than intravenous ustekinumab induction is associated with comparable circulating drug levels and early clinical response: a pilot study

“…Ustekinumab has previously been reported to have low rates of immunogenicity . Current literature suggests that the development of anti‐drug antibodies may not be as significant a factor as with other biologic agents and therefore the added benefit of immunomodulator therapy must be investigated further …”