ECCO 2016: Professor Stefan Schreiber (Kiel, Germany) discusses some of the issues in managing Crohn's disease.

In it for the long haul – managing the complexity of Crohn’s disease
by Maria Dalby
Michael Kamm (Melbourne, Australia), Remo Panaccione (Alberta, Canada) and Stefan Schreiber (Kiel, Germany).
When treating a condition like Crohn’s disease (CD) with its complex aetiology and pathogenesis, it is important to establish long-term treatment goals to not only achieve symptom resolution but also minimise the risk of long-term complications. Professor Michael Kamm from Melbourne, Australia chaired a symposium dedicated to optimising the use of biological therapies in CD. In his introduction he reminded the audience that CD is a condition that puts clinicians to the test both in the short and long term.
CD is a complex condition which manifests itself in and outside the gastrointestional tract. The underlying cause is thought to be a combination of genetic predisposition, environmental factors and a deficient host immune system.¹ Dr Remo Panaccione, from Calgary in Canada, predicted that, although this is in many ways a very exciting time for IBD specialists with several new therapeutic agents due to become available in the next few years, this will also increase the complexity of the decision-making in CD. Safety is paramount; the prospect of medical therapy for global suppression of the immune system is daunting for patients and it is important that the clinician respects these concerns in the discussion of benefit versus risk. Current anti-TNF biologics are highly effective as induction therapy in anti-TNF-naïve and anti-TNF failure patients, with response rates of 50-70% noted in clinical studies with infliximab^{2, 3} and adalimumab.^4-6 However, recent data from the TREAT registry shows that anti-TNF therapy is an independent predictor of serious infections in a population of 6,273 patients followed for more than 5 years.⁷ The increased risk of serious infection is particularly pronounced in patients aged over 65.⁸ The product labels of both infliximab and adalimumab contain lengthy warnings and precautions regarding the risk of not only infections but also malignancies, and some countries have also imposed ‘black box’ warnings over the risk of developing lymphoma on anti-TNF therapy. This information is available in the public domain and makes for challenging discussions with patients.
In contrast, the gut-selective anti-α4 integrin vedolizumab, which Professor Panaccione described as a “spectacular development” in IBD, is associated with favourable efficacy and safety profiles. A recently published analysis of integrated safety data from six clinical trials with vedolizumab comprising 2,830 patients with a total of 4,811 patient-years of exposure, showed no increased risk of any infection or serious infection associated with vedolizumab exposure.⁹ No cases of cases of progressive multifocal leukoencephalopathy (PML) were observed and only very few malignancies.⁹ Vedolizumab has been shown to maintain remission for up to 3 years¹⁰ which reflects the control of inflammation in the lamina propria. Results from an open-label extension of the GEMINI study programme indicate that CD and UC patients with a continued response to vedolizumab sustained long-term endoscopic healing.¹¹ Additional subgroup analyses from the GEMINI 2 study indicate that vedolizumab treatment is associated with shorter time to fistula closure¹² and resolution of extraintestinal manifestations^{13, 14} in CD, although these findings remain to be documented in prospective clinical trials.
The real-life clinical experience with vedolizumab that is emerging in the medical literature is largely consistent with its clinical trial profile and supports the finding that vedolizumab is highly effective for achieving a sustained clinical response and inducing remission in both biologic-naïve patients and those with previous exposure, with a favourable tolerability profile. Professor Stefan Schreiber, from Kiel in Germany, presented data from a number of cohorts that have been presented recently. In the Boston Massachusetts General Hospital (MGH) and Brigham and Women’s Hospital (BWH) multicentre cohort of 107 CD patients, most of them heavily pre-treated with active disease, response rates continued to increase beyond 6 weeks which suggests that some patients with previous exposure may take a bit longer to respond.¹⁵ Similar results were reported in the French early-access programme with 173 CD patients¹⁶ and the German Registry of 174 CD patients.¹⁷  The German Registry also highlighted a significant steroid-sparing effect of vedolizumab in both CD and UC.¹⁷ The safety profile in these cohorts is more complex than in controlled clinical trials as real-life patients will have more concomitant conditions and medications that would not be allowed in trials, but the overall trend is that vedolizumab is well tolerated. Smaller cohorts have also been published in Sweden¹⁸, Spain¹⁹ and the US^20-23 which confirm these findings. Real-world endoscopic data is as yet limited but indicates mucosal healing rates in the order of 20-30%.^{20, 21, 23-25} As more data becomes available on real-life use of vedolizumab, clinical practice is changing – up to 30% of patients in US centres are now receiving vedolizumab as their first biologic therapy.^26-30
 
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