There are numerous clinical drug trials underway into new treatments for IBD in adults; if found to be effective, trials can then be performed in children. One of these drugs being developed is called Vedolizumab. This has been found to be effective in reducing symptoms in adults with severe Crohn’s disease (CD) or ulcerative colitis (UC) which has not responded to conventional therapy including those who have been treated with anti-TNF drugs (infliximab/adalimumab). Vedolizumab is a humanised antibody but unlike infliximab or adalimumab it acts on a different receptor called an integrin, specifically anti α4β7. It works by stopping T lymphocytes (the body’s own inflammatory cells) heading into the bowel causing inflammation so is specific in its target. It has a longer time to achieving an improvement in symptoms, with a difference only seen at week 10, which improves again by week 14.
The aim of this study was to determine if Vedolizumab works in the paediatric population to improve symptoms and induce remission. This study had 21 patients with severe IBD, most had CD with 19% having stricturing disease (narrowings) and 12.5% penetrating (fistulas) thus confirming that the cohort is at the severe end of the spectrum of IBD. Patients were given induction dosing at 0, 2 and 6 weeks, then went to maintenance therapy and completed 22 weeks of treatment. The response was decided based upon clinical scoring of symptoms and blood tests. The study reported a decrease in clinical scoring at week 14, which persisted until week 22 when the study concluded, and a reduction in steroid use with 14/21 stopping steroids by week 22. There were several minor adverse events, mostly upper respiratory tract infections (colds); there were 12 serious events which resulted in hospital admittance, most commonly dehydration/vomiting and flare of disease.
The limitations of this study were that roughly a third of the patients were over 18 years of age so not paediatric any more. It was based in a single centre in North America and patients were selected by the doctors caring for them, so it is not clear exactly why each patient received the drug. The cohort had severe refractory IBD with nearly 40% having either narrowings or fistulas, which is not representative of all children with IBD. Although there was a reduction in steroid use, many remained on steroids when the study finished, and although there was an improvement in symptoms, 63% of CD and 40% of UC patients still had mild disease activity.
Despite the limitations of this study, this is another step forward to having another therapy that we can use in children with severe IBD that does not respond to our standard treatments. Although the improvements are modest, adult studies suggest that Vedolizumab takes longer to be effective, and perhaps by extending the length of the study, further improvement may be seen. However, even modest improvements in this severe group of patients is promising given that within this group of patients, 62% discontinued infliximab due to loss of response and 62% failing on 2 anti-TNF agents, leaving little therapies to improve symptoms. Another larger study based across several centres needs to be performed to ensure that the efficacy seen here can be replicated in more children with longer follow up, in order to learn for how long the drug should be given. Longer follow up and more patients will allow us to determine how safe this drug is and to uncover any other potential adverse effects.
FC January 2017