Crohn's Progression Unchanged Despite Advanced Therapies

Nicola M. Parry, DVM

February 15, 2018

Use of advanced therapies for Crohn's disease (CD) has not significantly altered the natural disease course and phenotypes compared with those reported before the era of biologic therapies, a recent study suggests.

"Despite an earlier and more aggressive treatment with immunomodulators and biological therapy, rates of surgery and disease progression were not significantly different from previous population-based inception cohorts 20 years ago," write Johan Burisch, MD, PhD, from North Zealand University Hospital, Frederikssund, Denmark, and colleagues.

"Furthermore, while we observed differences in choices of treatment between patients from Western and Eastern Europe, we found no difference regarding disease course and prognosis," they report in an article published online January 23 in Gut.

Although patients with CD now receive early and frequent treatment with immunomodulators and biological therapy, the effects of these treatment advances on long-term patient outcomes have been uncertain. Therefore, Burisch and colleagues analyzed data from the Epi-IBD cohort, a prospective population-based inception cohort of patients with inflammatory bowel disease diagnosed in 2010 from 29 centers in 22 European countries and Israel.

The study included 488 patients who were followed from the time of diagnosis for 5 years or until the date of their emigration or death; 404 (83%) were diagnosed in Western European and 84 (17%) in Eastern European centers.

During follow-up, 107 (22%) patients underwent resection and 176 (36%) were hospitalized at least once because of their CD. In addition, 49 (14%) patients who had received a diagnosis of nonstricturing, nonpenetrating CD progressed to either stricturing and/or penetrating disease.

These rates did not differ between patients from Western and Eastern European centers, the authors say.

However, the researchers found significant geographic differences in treatment patterns, with more patients in Western vs Eastern Europe receiving biological therapy (33% vs 14%) and immunomodulators (66% vs 54%; P < .01 for both treatments).

In contrast, more patients in Eastern Europe received 5-aminosalicylates (90% vs 56%; P < .05), the authors note.

The researchers did find that patients who received immunomodulators had a reduced risk for surgery
(hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2 - 0.6) and hospitalization (HR, 0.3; 95% CI, 0.2 - 0.5).

Burisch and colleagues emphasize that the strength of the Epi-IBD cohort lies in the prospective inclusion and follow-up of incident patients with inflammatory bowel disease in defined geographic areas. "The patients were unselected and represent the whole spectrum of disease severity," they write. "[T]herefore, the choices of treatment in this cohort are the results of community effectiveness rather than the requirements of a randomised controlled trial and all occurred in a real-life clinical setting."

Nevertheless, they acknowledge the need for future studies on risk stratification and to determine whether treat-to-target strategies significantly influence the course of CD.

When asked to commenting on the findings, David P. Hudesman, MD, Medical Director of the Inflammatory Bowel Disease Center at NYU Langone Health, New York City, agreed that, on the surface, the natural history of CD in this study is very similar to what has previously been reported.

However, "when you delve into the data, they show that earlier use of immunomodulator therapy reduces the rates of surgery and hospitalization, which is important," he told Medscape Medical News.

Dr Hudesman noted that the patients in this study who received biologics were likely different than those who received immunomodulators. Approximately 72% of the patients receiving biologic therapy had been previously treated with immunomodulators, which suggests that these may be more complicated patients.

For this reason, Dr Hudesman stressed that it is unfair to conclude that immunomodulator therapy performed better than biologic therapy in this study.

This study also highlights that treating to symptom resolution is not good enough, he said. In this real-world setting, the percentage of patients with moderate to severe disease decreased from 38% to 12% over 5 years. However, only 41% of the patients had a follow up colonoscopy after the first year, Dr Hudesman said.

Instead of merely treating to symptoms, Dr Hudesman stressed the need for more data examining the effects of treating to target; that is, healing of the mucosa.

This study was supported by grants from Kirsten og Freddy Johansens Fond as well as from Nordsjællands Hospital Forskningsråd. Multiple authors reported various financial relationships with one or more of the following companies: Janssen, MSD, Takeda, AbbVie, Biocure, Celgene, Ferring Pharmaceuticals, Hospira, Medivir, Pfizer, Tillotts Pharma, Vifor Pharma, Boehringer, Celgene, Mundipharma, Faes Farma, Falk Pharma, Kern Pharma Biologics, Otsuka, and Shire. Dr Hudesman has reported receiving consulting fees from Janssen, AbbVie, and Takeda.

Gut. Published online January 23, 2018. Abstract

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