Ustekinumab Beneficial in Refractory Crohn's Disease in Real World

By David Douglas

May 01, 2019

NEW YORK (Reuters Health) - A real-world observational study confirms the benefit of ustekinumab in patients with Crohn's disease (CD) previously exposed to other biologics, according to Belgian researchers.

"This study," Dr. Claire Liefferinckx told Reuters Health by email, "suggests that ustekinumab can be effective in CD patient despite previous failures to several lines of biologics - which is clinically very useful."

In an April 16 online paper in the Journal of Crohn's and Colitis, Dr. Liefferinckx of Erasmus Hospital, Brussels, and colleagues note that although the drug was recently approved in Europe for treating moderate to severe Crohn's disease, "long-term real-world data are currently scarce."

To investigate, the researchers examined data on 152 patients who started treatment with ustekinumab between 2016 and 2017. All except one had been exposed to at least one anti-TNF alpha agent, 82% had been exposed to two, and 70% had been exposed to two anti-TNF alpha agents and vedolizumab.

All patients underwent weight-based ustekinumab IV induction and maintenance with subcutaneous 90 mg injection every eight weeks.

At one year, 42.1% showed clinical response and 25.7% achieved clinical remission. The rates of steroid-free clinical response and remission were 38.8% and 24.3%, respectively, and 38.8% of patients discontinued therapy during follow-up.

In univariate analysis, patients with colonic disease were significantly more likely to have a clinical response at one year (odds ratio, 2.5). "This could be useful in clinical practice to help choosing the 'good biologic' for the 'good patient,'" Dr. Liefferinckx noted.

In multivariate analysis, BMI below 18 was negative predictor of remission (OR, 0.28). This, say the researchers, could be related to the severity of the underlying CD.

"A significant proportion of patients with arthralgia at baseline experienced a complete resolution of symptoms in correlation with clinical response but some patients without arthralgia at baseline developed arthralgia," the researchers note. However, none of these patients were evaluated by a rheumatologist, so the "results need to be interpreted with caution."

Other than de novo arthralgia, which caused one patient to discontinue therapy, there were only ten other adverse events and a total of 17 patients underwent surgery due to CD complications.

"Few adverse events across one year of follow-up were observed, confirming the safety profile," Dr. Liefferinckx said.

Dr. William J. Sandborn, director of the Inflammatory Bowel Disease Center at UC San Diego Health, in La Jolla, who was not involved in the study, told Reuters Health by email, "This real-world clinical experience from Europe is very informative, in particular since it includes Crohn's disease patients that failed both anti-TNF and vedolizumab therapy, and continues to show that ustekinumab is both safe and effective, even in very refractory patients."

The study had no commercial funding. Several of Dr. Liefferinckx coauthors report ties to Janssen, which markets ustekinumab as Stelara.


J Crohns Colitis 2019.