Fecal microbiota profile predicts ustekinumab response in Crohn's

Last Updated: 2018-03-22

By Reuters Staff

NEW YORK (Reuters Health) - Data on patients' fecal microbiota can be used to predict their response to ustekinumab therapy for Crohn's disease, researchers report.

Earlier studies have shown that the bacterial gut microbiota correlates with disease severity and can predict clinical response to treatment of Crohn's disease with certain biologics. Whether this extends to responses to anti-interleukin-23 therapy remains to be seen.

Dr. Patrick D. Schloss from the University of Michigan, in Ann Arbor, and colleagues investigated the association between fecal microbiota and response to ustekinumab, a monoclonal antibody directed against the shared p40 subunit of IL-12 and IL-23, among patients with Crohn's disease who participated in the phase 2 CERTIFI study.

Fecal microbiota signatures developed using models trained on subjects' baseline microbiota predicted treatment remission with a sensitivity of 81%, a specificity of 77% and an overall accuracy of 84%, the researchers report in mBio, online March 13.

Similarly, the microbiota model predicted treatment response with a sensitivity of 88%, a specificity of 56% and an overall accuracy of 76%.

The prediction accuracy did not improve significantly with the addition of clinical data.

Baseline microbial diversity was 1.7 times higher, and baseline Faecalibacterium and Bacteroides were significantly more abundant, in subjects who were in remission six weeks after treatment compared with those who still had active disease.

Moreover, microbial diversity increased significantly through 22 weeks after induction among patients who responded to ustekinumab treatment.

Fecal microbiota at week six of treatment accurately distinguished between ustekinumab responders and nonresponders.

"These predictive biomarkers will need to be validated using independent cohorts in future studies," the researchers note. "Additionally, the positive and negative associations between the microbiota and Crohn's disease allow us to predict the types of mechanisms most likely to alter the microbiota in order to increase the likelihood of achieving a therapeutic response or to monitor disease severity."

"Prior to the initiation of therapy, patients could have their fecal microbiome analyzed," they suggest. "The microbial community data could then be used to direct the modification of a patient's microbiota prior to or during treatment with the goal of improving treatment outcomes."

"Since it has been shown experimentally that the microbiome can alter the efficacy of treatments for a variety of diseases, if fecal microbiota can be validated as biomarkers to noninvasively predict response to therapy, then patients and clinicians will be able to more rapidly ascertain effective therapies that result in increased patient quality of life," the authors conclude.

Dr. Schloss did not respond to a request for comments.

Janssen Research and Development provided financial and technical support for the study and employed several of the authors.

SOURCE: http://bit.ly/2pxYPLG

mBio 2018.