The UNITI studies have shown ustekinumab is effective at inducing and maintaining clinical remission in Crohn’s disease patients.
Ustekinumab does not significantly improve overall extraintestinal manifestations (EIM) for patients with Crohn’s disease.
The recent UNITI trials showed that the biologic was effective at inducing and maintaining clinical remission in this patient population but did not show much data in regard to the effectiveness of ustekinumab for the treatment of extraintestinal manifestations.
A team, led by Neeraj Narula, MD, Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, McMaster University, evaluated the efficacy of ustekinumab in the treatment of EIMs in a post-hoc analysis of the UNITI trials.
Extraintestinal manifestations are frequently reported by patients and can reflect the systemic nature of inflammatory bowel disease (IBD). In particular with Crohn’s disease patient, the prevalence of this condition is between 6-47%. Crohn’s disease patients tend to suffer from EIMs more frequently than patients with ulcerative colitis.
In addition, up to 25% of IBD patients can have multiple extraintestinal manifestations.
Ustekinumab is a human 1gG1K monoclonal antibody that inhibits the biologic activity of cytokines interleukin-12 and interleukin-23 through the common p40 subunit.The treatment also has shown efficacy in treating chronic plaque psoriasis and active psoriatic arthritis.
The researchers used data from the UNITI-1/2 and IM-UNITI from the Yale Open Data Access Project and identified 941 patients eligible for ustekinumab induction and an additional 263 patients eligible for maintenance therapy.
The investigators sought primary outcomes of EIM resolution at week 6 in ustekinumab and placebo-treated participants using the chi-square test and assessed EIM resolution at week 52.
The team also used McNemar’s test to compare the proportion of patients reporting active extraintestinal manifestations at weeks 6 and 52 when compared to baseline.
There were 941 patients treated with ustekinumab in the UNITI-1/2 study, 504 of which had 527 EIMs at baseline.
However, the results show there was no significant difference in EIM resolution in patients treated with the study drug (n = 186; 36.9%) compared to placebo (n = 90; 39.1%; P = 0.564) at week 6.
There was also no significant difference in overall extraintestinal manifestations (EIMs) resolved at week 52 in patients treated with continuous ustekinumab (n = 91; 76.4%) compared to placebo (n = 72; 80.0%; P = 0.542).
While many EIMs were reduced in prevalence compared to baseline at treatment initiation, only erythema nodosum was more likely to improve at week 52 on ustekinumab compared to placebo.
“The results of this post hoc analysis of moderate to severe CD patients suggest ustekinumab does not lead to improvement in overall EIM resolution as compared to placebo,” the authors wrote. “Further controlled data using validated techniques with assessments performed by trained physicians should be considered to further explore whether UST could be an efficacious therapy for IBD patients with EIMs.”
The study, “The impact of ustekinumab on extraintestinal manifestations of Crohn's disease: A post hoc analysis of the UNITI studies,” was published online in United European Gastroenterology Journal.