Disappointing results from a phase II study suggests the inhibition of IL-17 may not be a potential target for treating Crohn’s disease.

Writing in the American Journal of Gastroenterology the study authors noted that Interleukin (IL)-17 has an important role in immune-mediated diseases. Therapy targeting the IL-17 pathway had demonstrated encouraging results in other inflammatory diseases such as rheumatoid arthritis and psoriasis, but a small study had shown this had not translated to the treatment of Crohn’s disease (CD).

In the current study the research team randomised 130 patients with moderate to severe disease to the human monoclonal antibody brodalumab at a dose of 210mg, 350mg or 700mg at baseline and week four, or to placebo.

The study primary endpoint was the proportion of patients who achieved clinical remission, defined as a CDAI score of ≤ 150 points at week six.

Due to a disproportionate number of cases of worsening of CD in the active treatment meant the trial was stopped early.

The odds ratio of worsening CD in all broadlumab treated patients compared to placebo was 6.64 (95% CI 1.48, 29.88). There was no evidence of meaningful efficacy at any time point in the active treatment group.

The research team said the findings were consistent with a randomised controlled trial of secukinumab, a monoclonal antibody directed toward IL-17 isotype 1, which also found a significant difference in CDAI in favour of placebo.

In that study, and the current study, unfavourable responses to IL-17 antagonism were potential driven by patients with elevated inflammatory markers. Patients with worsening disease also had higher CRP and slightly elevated fecal calprotectin at baseline compared to those who did not have worsening disease.

“It is possible that blocking of IL-17A may interfere with a protective function of IL-17A in the intestine,” they wrote.

“On the basis of these data, further evaluation for brodalumab as a treatment for CD does not appear to be warranted,” they concluded.