Day 3 of DDW was again full of new, potentially practice-changing evidence. The day started with the Clinical Science Plenary session during which data was presented from the first prospective randomized trial comparing the use of cyclosporin and infliximab in patients with severe acute ulcerative colitis that had failed to respond to intravenous corticosteroid treatment. The study was designed to show the superiority of cyclosporin, i.e. that patients failed less frequently on cyclosporin therapy than on infliximab. It was estimated that 60% of patients would fail treatment on infliximab.
In fact, the results showed that cyclosporin was not more effective than infliximab in achieving short-term remission and avoiding urgent colectomy. Data showed that the rates of treatment failure were 60% with cyclosporin vs 54% with infliximab, while response rates at Day 7 were 84% vs. 86%.While most doctors seem to accept that there is still a role for cyclosporin in the treatment of acute severe ulcerative colitis, its future position in the treatment algorithm is unclear.
In a later session, there was a fascinating overview of the latest research in inflammatory bowel disease given by Dr Stephan Targan in the Presidential Plenary session. Dr Targan chose to focus his presentation on the explosion of data that has been generated in the last two years examining the genetic causes of Crohn’s disease and ulcerative colitis. He suggested that while Crohn’s disease and ulcerative colitis shared many gene loci and biologic pathways, the two diseases were different and each had unique disease-related pathways. In fact, Dr Targan suggested that both diseases could be considered as heterogeneous, and to be comprised of multiple diseases, each with its own set of susceptibility genes.
Dr Targan highlighted how these genetic loci could not just predict disease phenotype and likely prognosis but could also predict response rates to drug therapy. He wrapped up by giving an example of how knowledge of both the human genome and the genes that lead to IBD had informed and shaped the development of mouse models for inflammation, which in turn were now transforming our understanding of how fibrostenotic disease types progressed.
In the afternoon, the first key presentation of the ‘Controlled Trials in IBD’ session showed data from a trial evaluating the efficacy and safety of adalimumab for the induction and maintenance of clinical remission in patients with moderate-to-severe ulcerative colitis.
Its co-primary endpoints were proportion of patients with clinical remission at Week 8, and clinical remission at Week 52. Major secondary endpoints included sustained clinical remission at both Week 8 and 52, clinical response and mucosal healing at Week 8, Week 52, and both Week 8 and 52.
Results showed that significantly more adalimumab-treated patients achieved clinical remission, clinical response, and mucosal healing at Week 8, Week 52, and both Week 8 and 52, compared with placebo. Incidence rates of serious and infectious adverse events were similar between placebo and adalimumab groups.
In conclusion, the presenter determined that adalimumab was efficacious in inducing and maintaining clinical remission in patients with moderate-to-severe UC who did not adequately respond to conventional therapy with oral corticosteroids and immunosuppressants. It was also clear that its efficacy was stronger in patients that were naive to anti-TNF therapy. Based on this data and that previously published, it seems likely that the use and uptake of adalimumab in UC, once approved, will mirror that seen in Crohns’ disease. We will examine this issue in more detail in the coming months.
In the second key presentation of the ‘Controlled Trials in IBD’ session data was presented from a randomized, multicenter, phase III study of infliximab in pediatric moderate-to-severe ulcerative colitis patients. The study looked at the efficacy of three dosing regimens of infliximab in inducing clinical response and evaluated its safety during induction and maintenance treatment. Its primary endpoint was clinical response at wk8.
The results showed that infliximab induced clinical response at wk8 in 73.3% of patients while 40.0% were also in clinical remission. Furthermore, at the same point 68.3% of patients achieved mucosal healing.
At the end of the maintenance phase (wk54) there was a numerically greater proportion of patients in remission in the patients dosed every 8 weeks vs those dosed every 12 weeks although this did not reach statistical significance. It was concluded that infliximab is effective and safe for pediatric patients with moderately to severely active ulcerative colitis with results comparable to those of the ACT trials.
Finally, there were two additional presentations during this session: one based on data from the US study of budesonide MMX in treating ulcerative colitis; the second based on a Phase II trial of tofacitinib, the JAK 3 oral inhibitor, in Crohn’s disease. These presentations will be reviewed together with other emerging therapies in a later article.