In the JournalsPerspective

Entyvio ‘should be’ first choice for patients with UC who previously failed Remicade

In a direct comparison with Humira, Entyvio won out as the top choice for second line therapy for patients with ulcerative colitis who failed therapy with Remicade, according to research published in Inflammatory Bowel Diseases.

Massimo Claudio Fantini, MD, PhD, from the University of Rome, and colleagues wrote that there are no solid data to support which drug should be used as a follow-up in patients who do not respond or lose response to Remicade (infliximab, Janssen).

“At the moment, there is no clear indication on the most appropriate second-line biological therapy in case of failure to [infliximab], and in the absence of head-to-head comparative efficacy data, the choice between a second anti-TNF-alpha or the anti-integrin [Entyvio (vedolizumab, Takeda)] is often based on clinician’s personal experience, drug availability, and economic issues,” they wrote.

Researchers analyzed clinical records of 161 patients with UC who failed infliximab therapy and were candidates to receive either Humira (adalimumab, AbbVie) or vedolizumab. The primary endpoint was therapeutic failure at week 52, and secondary endpoints included therapy discontinuation at weeks 8, 24 and 52, discontinuation-free survival and safety.

Patients in the study were either primary (n = 9.2%) or secondary (n = 83, 51.7%) infliximab failures or infliximab intolerants (n = 63, 39.2%). Researchers determined that 64 patients received adalimumab (40%) and 97 patients received vedolizumab (60%).

After 52 weeks, 37.5% of patients on adalimumab and 28.9% on vedolizumab had therapeutic failure. The failure rate was significantly higher in the adalimumab group compared with vedolizumab among patients who experienced secondary failure to infliximab (48% vs. 22.4%; P = .035). The therapy discontinuation-free survival was also higher in the group of secondary failure who received vedolizumab compared with adalimumab (OR = 2.79; 95% CI, 1.23–6.34).

Investigators found no difference in the failure and biologic discontinuation-free survival in the infliximab primary failure and intolerant subgroups.

“In a real-life setting and in the absence of therapeutic drug monitoring, although [vedolizumab] and [adalimumab] might be equally effective in UC patients who stopped [Infliximab] due to intolerance, [vedolizumab] should be considered the therapy of choice in patients with secondary failure,” Fantini and colleagues concluded. – by Alex Young

Disclosures: Fantini reports serving as a speaker or consultant and advisory board member for AbbVie, Janssen-Cilag, MSD, Pfizer, Takeda and Zambon. He also reports research funding from Janssen-Cilag and Pfizer Please see the full study for all other authors’ relevant financial disclosures.

In a direct comparison with Humira, Entyvio won out as the top choice for second line therapy for patients with ulcerative colitis who failed therapy with Remicade, according to research published in Inflammatory Bowel Diseases.

Massimo Claudio Fantini, MD, PhD, from the University of Rome, and colleagues wrote that there are no solid data to support which drug should be used as a follow-up in patients who do not respond or lose response to Remicade (infliximab, Janssen).

“At the moment, there is no clear indication on the most appropriate second-line biological therapy in case of failure to [infliximab], and in the absence of head-to-head comparative efficacy data, the choice between a second anti-TNF-alpha or the anti-integrin [Entyvio (vedolizumab, Takeda)] is often based on clinician’s personal experience, drug availability, and economic issues,” they wrote.

Researchers analyzed clinical records of 161 patients with UC who failed infliximab therapy and were candidates to receive either Humira (adalimumab, AbbVie) or vedolizumab. The primary endpoint was therapeutic failure at week 52, and secondary endpoints included therapy discontinuation at weeks 8, 24 and 52, discontinuation-free survival and safety.

Patients in the study were either primary (n = 9.2%) or secondary (n = 83, 51.7%) infliximab failures or infliximab intolerants (n = 63, 39.2%). Researchers determined that 64 patients received adalimumab (40%) and 97 patients received vedolizumab (60%).

After 52 weeks, 37.5% of patients on adalimumab and 28.9% on vedolizumab had therapeutic failure. The failure rate was significantly higher in the adalimumab group compared with vedolizumab among patients who experienced secondary failure to infliximab (48% vs. 22.4%; P = .035). The therapy discontinuation-free survival was also higher in the group of secondary failure who received vedolizumab compared with adalimumab (OR = 2.79; 95% CI, 1.23–6.34).

Investigators found no difference in the failure and biologic discontinuation-free survival in the infliximab primary failure and intolerant subgroups.

“In a real-life setting and in the absence of therapeutic drug monitoring, although [vedolizumab] and [adalimumab] might be equally effective in UC patients who stopped [Infliximab] due to intolerance, [vedolizumab] should be considered the therapy of choice in patients with secondary failure,” Fantini and colleagues concluded. – by Alex Young

Disclosures: Fantini reports serving as a speaker or consultant and advisory board member for AbbVie, Janssen-Cilag, MSD, Pfizer, Takeda and Zambon. He also reports research funding from Janssen-Cilag and Pfizer Please see the full study for all other authors’ relevant financial disclosures.

    Perspective
    Sara Horst

    Sara Horst

    As treatment options for ulcerative colitis expand, medication sequencing is becoming increasingly important. Fantini et al undertook a retrospective analysis from eight Italian IBD centers to understand how patients with ulcerative colitis who had infliximab failure/intolerance would respond to either adalimumab or vedolizumab. Overall, there was no difference in those who failed either second-line medication. However, in patients with secondary failure to infliximab, those who started vedolizumab had lower treatment failures.

    Other data points to vedolizumab as a second-line medication having improved outcomes over anti-TNF. A multicenter, U.S.-based consortium found that vedolizumab-treated patients with UC had significantly higher 12-month cumulative rates of clinical remission and endoscopic healing compared to anti-TNF. Most of these patients had prior anti-TNF exposure, although propensity scoring analysis was done to try to control for this. It is important to note for these studies, the second-line medication choice was not randomized, which could introduce bias into the treatment effect.

    Recently, a phase 3b, double-blind, multicenter trial performed a head-to-head comparison of adalimumab vs. vedolizumab in more than 600 patients with UC. This study found statistically improved overall clinical remission and endoscopic healing at week 52 with vedolizumab (most patients were anti-TNF naive). Interestingly, there was no difference in clinical remission or endoscopic healing in patients with prior anti-TNF exposure/failure (20% of both treatment arms).

    Where does this leave us for treatment options for patients with UC who fail anti-TNF therapy? Retrospective, “real-world” data suggest that vedolizumab may offer lower failure rates, especially in patients with secondary failure of infliximab. However, we need to better understand how to better position the first therapy, ie, which mechanism of action is best for the individual patient. Therefore, in the future, what “second-line” medication to use will become a less important question to answer.

    References:

    • Faleck D, et al. OP26. Presented at: Congress of the European Crohn’s and Colitis Organisation; Feb. 14-17, 2018; Vienna.
    • Favale A, et al. Inflammatory Bowel Disease. 2019;doi:10.1039/ibd/izz057.
    • Schreiber S, et al. OP34. Presented at: Congress of the European Crohn’s and Colitis Organisation; Mar. 7-9, 2019; Copenhagen.
    • Sara Horst, MD, MPH
    • Associate Professor, Department of Gastroenterology, Hepatology, & Nutrition
      Vanderbilt University Medical Center

    Disclosures: Horst reports serving as a consultant for Boehringer Ingelheim and Janssen.

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