p40 subunit of interleukin 12 and 23 which is blocked by ustekinumab . More recently , he added , JAK inhibitors such as tofacitinib and S1P modulators such as ozanimod have also been approved . But despite this wider range of therapeutic options , Dr Panés said that it seems ‘ we have reached a ceiling of efficacy that is around 30 % of patients being in remission one year after starting treatment .’ In other words , the majority of patients in receipt of monotherapy are not completely free of symptoms . As a clinician , he feels that the overarching aim of any treatment is that ‘ the patient is completely in remission and without symptoms because even mild symptoms can lead to a deterioration in their quality of life so that they underperform in all aspects of life .’
He mentioned how some 20 years ago , it was found that the combination of infliximab with azathioprine provided superior relief of symptoms compared to monotherapy . Despite this positive result , it seemed to have become lost in antiquity and no subsequent studies have examined the efficacy of combination
The introduction of biologics has had a profoundly positive impact on the management of ulcerative colitis , both in the short- and long-term therapy in ulcerative colitis . He felt that with the introduction of guselkumab ( which targets interleukin 23 ) and golimumab , which is an anti-TNF , an opportunity has opened to test a combination of these two drugs even before guselkumab was formally approved . The aim of the study as he put it was to ‘ test whether combination therapy with an anti-TNF and an anti-IL 23 was more effective than either monotherapy alone .’ The study included patients with moderate and severe ulcerative colitis and randomised them to monotherapy or combination induction therapy . The findings , he says , were impressive , showing that the number of patients achieving all of the endpoints tested , including clinical remission , i . e ., the complete absence of symptoms ‘ was doubled ( 48 % vs 23 %) by the combination therapy relative to each monotherapy alone ’ and for each of the outcomes assessed . The study also examined the safety of treatment as biologics are known to suppress the immune system and thus increase the risk of infection . Fortunately , as Dr Panés explained , there were no safety concerns identified and the incidence of adverse effects was no higher with combination therapy than for each monotherapy .
Q What are the next steps after VEGA ?
A While VEGA represented a ‘ proof of concept ’ study , clearly demonstrating the benefit of combination induction therapy , Dr Panés said that it was now important to progress towards Phase III trials . In fact , he says that the aim of these studies is to ‘ compare the efficacy and safety of combination therapy for one year .’ His believes that using the combination therapy over an extended period of time will afford a greater clinical benefit for patients . Nevertheless , he feels that there are still several unanswered questions .
For instance , it is necessary to define the best strategy for induction and equally important , is the identification of predictive biomarkers that can be used to identify which patients will respond to either monoor combination therapy . As Dr Panés explained , ‘ two patients with almost identical disease severity might not respond equally to the same therapy ’ and it is therefore necessary to have some guidance as to which approach would best suit an individual patient .
The impact of the findings from the VEGA study is likely to be significant and lead to changes in clinical practice . However , there is still much to be achieved , especially the identification of prognostic treatment biomarkers , but it seems highly likely that in the coming years , a larger number of patients with ulcerative colitis will be able to achieve clinical remission that will enable them to lead as normal a life as possible .
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