Vedolizumab a “new chapter” for IBD therapy beyond anti-TNF
The α4β7 integrin antibody vedolizumab continues to show efficacy and safety in patients with inflammatory bowel disease (IBD) in an era beyond tumour necrosis factor (TNF) inhibitors, according to a presentation at the annual Advances in Inflammatory Bowel Diseases (AIBD) 2018 meeting.
Although TNF inhibitors have been commonly used for treating IBD, these drugs are “far from perfect” in terms of efficacy in IBD, said Professor Brian Feagan from the Western University in Ontario, Canada, noting that the response rates for these agents were only about 30–40 percent. [Gastroenterology 2007;132:52-65]
Also, being a systemic immunosuppressive agent, an Achilles’ heel of the drug is the increase in serious infection risk, he highlighted. “Serious infection is an important limitation [of the drug], and immunization to pneumococcal, influenza, varicella zoster virus, and human papillomavirus is critical.”
The monoclonal antibody vedolizumab binds to α4β7 integrin, leading to inhibition of adhesion and trafficking of lymphocytes in the gut which mediate inflammation.
“Vedolizumab is the first gut-selective agent, and it has an unprecedented safety record,” said Feagan. The combined rates of any infections in UC and CD patients were lower with vedolizumab compared with placebo after adjusting for exposure time (63.5/100 patient-years vs 82.9/100 patient-years). Similar results were seen for upper and lower respiratory tract infections. [Gut 2017;66:839-851] A meta-analysis of real-world study also support the low incidence of any infection and Clostridium difficile infection in patients treated with vedolizumab. [Aliment Pharmacol Ther 2017;46:3-15]
Based on results from the GEMINI studies, vedolizumab has been approved for treating moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD).
In the double-blind GEMINI 1 study which enrolled 895 patients with UC, response rates were 47.1 percent in the vedolizumab group and 25.5 percent in the placebo group at week 6 during the induction phase (p<0.001). The difference in clinical remission rates between groups became more pronounced at week 52 during the maintenance phase, as achieved by >40 percent of patients who continued vedolizumab compared with 15.9 percent of patients who switched to placebo (p<0.001). [N Engl J Med 2013;369:699-710]
Although between-group difference in clinical remission response was statistically significant at week 6 during induction in the GEMINI 2 study involving 1,115 patients with CD, the clinical relevance of just a 7-percentage point difference was unclear (14.5 percent vs 6.8 percent; p=0.02), which according to Feagan, casts doubts on the induction potential. [New Eng J Med 2013;369:711-721]
However, another study showed that a longer induction period for 10 weeks yielded clinically meaningful effect with vedolizumab vs placebo for remission response (21.7 percent vs 11.0 percent; p=0.0008) rather than a <4-percentage point difference at week 6 — indicating that “one needs to look at 10–12 weeks induction for assessing efficacy [rather than just 6 weeks in the case of vedolizumab]”, according to Feagan. [Gastroenterology 2014;147:618-627]
“There are no surprises in real-world experience and it’s supportive of a very appropriate therapeutic index for use in both UC and CD,” Feagan added. The therapeutic benefits of vedolizumab in CD in terms of clinical response, clinical remission, and steroid-free remission were also seen in real-world cohorts across UK, Germany, France, and the US. [Frontline Gastroenterol 2017;8:196-202; Aliment Pharmacol Ther 2016;43:1090-1102; Clin Gastroenterol Hepatol 2016;14:1593-1601; Inflamm Bowel Dis 2015;21:2879-2885]
“Vedolizumab is an effective induction therapy in both UC and CD, even more so for maintenance,” he said. “The development of vedolizumab and its efficacy and safety in CD and UC is really a new chapter for therapeutics for IBD."