Crohn’s disease - medical therapy, a changing paradigm: an interview with Igor Khalif

In April this year, the first regional educational masterclass organised by the ESCP in cooperation with the European Crohn's and Colitis Organisation (ECCO), will take place in Moscow, Russia. This inaugural masterclass will concentrate on Ulcerative Colitis (UC) and Crohn's disease (CD) and here keynote speaker, Professor Igor Khalif (State Scientific Centre for Coloproctology, Moscow, Russia), examines the role of medical therapy in treating Crohn's disease.

“It is well-known that prevalence of Crohn's disease is rising world-wide and is estimated to be about 40 in every 10 000 persons. Unfortunately, the lack of an established registry makes estimation of this figure for Russia impossible,” explains Professor Khalif. “According to the Russian Ministry of Health record in 2013 a total of 6500 patients with Crohn’s disease were hospitalized, which is quite similar to European figures.”

Currently there are four major theories of Crohn’s disease pathogenesis; genetic predisposition, influence of environment, defects of immune response particularly innate immunity, and disturbances of intestinal microbiota. However, it is obvious that none of these defects can trigger Crohn’s disease as individual component, but rather their combination after an environmental trigger produces Crohn’s disease manifestation.

In 2014 the Russian Gastroenterology and Coloproctology associations, as well as the Russian IBD society, published guidelines for the treatment of Crohn’s disease. According to Professor Khalif, the guidelines are mostly in an accord with the ECCO and American College of Gastroenterology (ACG) guidelines and incorporate only well-established therapies such as aminosalycylates, corticosteroids, immunosupressants and biologics.

“We prefer to use a step-up approach in treatment of Crohn’s disease because of the lack of widespread IBD centres and high probability that CD patients can be simply lost without qualified help and monitoring,” he adds. “This led us to recommend constant maintenance therapy with immunosuppressants and/or biologics and advocate against aminosalycylates in CD. We also paid attention to the problem, not previously addressed in Russia, of continuing maintenance therapy and monitoring after the refferal of a CD patient from gastroenterologist to a colorectal surgeon.”

Currently, there are more than a dozen novel therapies that have the possibility of becoming available within the next few years. Most of them are targeted at different components of immune response. For a long time, only anti-TNFs were available. However, in 2015 several drugs such as vedolizumab approved for CD, and tofacitinib and ustekinumab approved for psoriatic arthritis, were registered in Russia. These drugs are currently undergoing scrutiny in clinical trials for treating CD and it is hoped the outcomes will provide much needed data on the viability of adding them to the arsenal of CD therapies.

Apart from definite indications for surgery, such as bowel perforation or toxic dilatation, the decision in other situations, such as internal fistulae, abdominal abscesses in CD or fulminant colitis, remains difficult according to Professor Khalif, even for a multidisciplinary team involving both gastroenterologists and surgeons when deciding the optimal treatment.

He claims that timing remains crucial, although there is as yet no good data about the prognosis of salvage therapy effectiveness in severe attack, as well as the outcome of abdominal abscesses after their percutaneous drainage. Therefore, the decision to operate or treat less aggressively can also be influenced by the patient’s ability to come for scheduled monitoring, their financial abilities (such as insurance coverage of biologics), as well as by the experience of local surgeons. Other important factors include the fertility of patient (particularly important in pouch-surgery), previous steroid therapy and access to novel imaging modalities such as MRI.

With regards to outcome, the best-known outcome remains endoscopic remission. The Pivotal IBSEN study, as well as other long-term follow-up studies, perfectly demonstrated that complete disappearance of endoscopic signs of disease predicts long-term remission and decreases the risk for surgery. This approach is particularly important in Crohn’s disease, when absence of marked ulceration after bowel resection lets the multi-disciplinary team predict no upcoming relapse and thus precludes unnecessary step-up in therapy. However, another as yet un-addressed outcome is patient’s quality of life; even patients in complete remission of CD can present with IBS-like syndrome or with psychological conditions such as cancerophobia or depression.

“Although there continues to be considerable data accumulated on ‘typical’ controversies, such as step-up vs step-down therapy or surgery vs second-line salvage therapy in severe attack, some ‘old’ problems remain un-addressed,” Professor Khalif concludes. “What is the optimal dose and tapering scheme of glucocorticosteroids? Is there an advantage of early resection in complicated yet localized Crohn’s disease, such as terminal ileitis vs multiple lines of therapy? For how long should the maintenance therapy be held? Let’s hope that the upcoming Moscow conference will shed light on these and other controversies in IBD treatment.”

The ESCP/S-ECCO joint regional masterclass in Moscow is supported by an education grant from