Crohn’s disease (CD) is a progressive disorder and the achievement of mucosal healing lowers the risk of necessary surgery, according to Julián Panés (Spain). Yet mucosal healing alone is insufficient now that CD treatment goals are changing. This statement opened the Takeda satellite symposium ‘Targeting Mucosal Healing; Optimising Results With Early Appropriate Therapy In Crohn’s Disease’ held at the UEGW 2017 in Barcelona.
The treatment goals have evolved from achieving clinical remission to achieving corticosteroid-free remission, followed by mucosal healing and, finally, transmural healing. Panés stressed the fact that early intervention with treatment based on biological medical products is crucial in view of the better long-term outcomes. Thus, through early combined immunosuppression, more patients achieved symptomatic remission than those given conventional therapy. Also, in each case, the time to the first hospital admission, surgery or complication was significantly longer with early treatment (HR 0.73 [95%CI 0.62-0.86, p<0.001]).
Laurent Peyrin-Biroulet (France) stated that not only the symptoms of a CD patient should be treated, but also the intestinal inflammation. This encompasses treatment with a compound goal (clinical and endoscopic remission), or STRIDE, in which endoscopic remission means the absence of ulceration during an ileocolonoscopy. Although this definition is used often in CD studies, according to Peyrin-Biroulet there are drawbacks to it. It ignores the persistent lesions such as erosion and erythema.
Next, Charlie Lees (United Kingdom) discussed what the achievement of the changing goals for treatment with vedolizumab – the only intestine-specific integrin inhibitor with marketing authorisation for moderate to severe CD/UC – means. From the GEMINI 2 and 3 pooled post-hoc analyses, it followed that clinical remission through vedolizumab is more pronounced in anti-TNF-naive patients. In week 52, among the total population, this was 48.9% compared with 26.9% for the placebo, vs 37.7% compared with 21.6% for the placebo. The results of the composite score for abdominal pain and the amount of liquid/very soft faeces clearly demonstrates that vedolizumab has an effect by week 2. Here, too, the results among anti-TNF-naive patients are stronger (-21.3% in week 2 vs -15.7% for the total population).
With the application of the treat-to-target strategy through the STRIDE concept, 21% of the patients in the long-term (3.2 years) GEMINI-extension study achieved combined histological and endoscopic healing. Partial healing occurred in 38% of them and full healing (no ulcers) occurred in 29% of these patients. Real-world data support this. Two separate studies show that in week 22 and in weeks 30-54, 30% of the patients achieved mucosal healing, while 58% of the patients in a third study had no ulcers/erosions in week 52. More data on mucosal healing is still to come, promised Lees: the VERSIFY study (n=100) will be presented during ECCO 2018.
Achieving the treatment goal is one thing, but maintaining this result is the ultimate goal, stated Lees. Over the last 20 years, a response decline of ≥50% has been observed for anti-TNFs. Based on the 5-year data from the GEMINI 2 extension study, he illustrated that the clinical remission achieved with vedolizumab continues for years. Also, the drop-out rate with vedolizumab is low compared with that for anti-TNFs. In addition, there are safety issues connected to anti-TNFs, such as severe infections. Vedolizumab has no such drawbacks, since it now seems that the number of infections is lower than is the case with the placebo. And real-world data confirm the favourable safety profile of vedolizumab: this qualification has since been included in the ECCO 2016 CD Consensus guidelines. Finally, an American real-world data study conducted among biological-naive patients clarified that patients that were treated with vedolizumab for a year experienced fewer IBD-related hospital admissions than those patients that were given infliximab for a year (12% vs 18%). Vedolizumab patients also stay out of the hospital longer with an average time to the first IBD-related hospitalisation of 153 days vs 98 days for infliximab patients.
The final goal of treatment is to delay the progression of the disease. To achieve this, therapy should be started early. More specifically, this means within the window of opportunity between diagnosis and the early onset of illness. Besides, it seems azathioprine has no extra value in early treatment, according to the GETAID study. Compared with the placebo, the difference with the lasting steroid-free remission is 7.6% (95%CI -9.2 to 24.4%, p=0.48). Also, for longer term disease and patients older than 50, azathioprine is not the first choice since it increases the risk of lymphoma.
In conclusion, it can be said that prior to treatment it should be ascertained which patients are eligible for early intervention. In choosing the treatment, the risks and benefits should be carefully considered. During the treatment, a treat-to-target strategy should be followed and the treatment should be optimised, in which monitoring is essential for long-term verification.