In patients with ulcerative colitis (UC) treated with ustekinumab, the achievement of histo-endoscopic mucosal healing after induction therapy is associated with lower disease activity at the end of maintenance therapy than either histologic or endoscopic improvement alone, according to the results of a study published in Gastroenterology.
It is not clear whether endoscopy alone is the optimal method to evaluate mucosal inflammation and its resolution in UC. Histologic assessment of the colonic mucosa based upon endoscopic biopsies provides direct assessment of mucosal inflammation and epithelial integrity at the cellular level and therefore may provide a more accurate assessment of the disease process than endoscopy. Ustekinumab induces and maintains histologic improvement in patients with UC, but the clinical relevance of this end point alone, and in combination with endoscopic improvement, is unknown.
Researchers sought to evaluate the clinical relevance and validity of the histologic, endoscopic, and histo-endoscopic end points and their associations with clinical and biological outcomes of ustekinumab in moderately-to-severely active UC patients (ClinicalTrials.gov identifier NCT02407236).
Histologic improvement was significantly (P <.0001) associated with clinical remission, lower mean disease activity scores, and greater improvement in disease activity at the end of the induction and maintenance studies. Ustekinumab induced and maintained significantly higher rates of histologic improvement at induction week 8 and maintenance week 44 compared with placebo when more stringent definitions of histologic improvement were used.
Histologic improvement and endoscopic improvement following induction were associated with 10% to 20% higher rates of histo-endoscopic mucosal healing, clinical remission, and corticosteroid-free remission at week 44 (all P <.05) in patients who received ustekinumab maintenance therapy. At week 44, 61% of patients with histo-endoscopic mucosal healing after induction therapy achieved clinical remission, compared with 39% of patients (P =.0983) and 34% of patients (P =.0009) with endoscopic or histologic improvement alone after induction, respectively.
Study limitations include an inability to assess outcomes beyond maintenance week 44. Results may also not be generalizable to other populations.
“[A]n outcome of histo-endoscopic mucosal healing provides additional information regarding subsequent clinical status that endoscopy and histology alone do not,” the authors concluded.
Disclosure: This clinical trial was supported by Janssen Research & Development, LLC (Spring House, PA). Please see the original reference for a full list of authors’ disclosures.
Li K, Marano C, Zhang H, et al. Relationship between combined histologic and endoscopic endpoints and efficacy of ustekinumab treatment in patients with ulcerative colitis [published online August 24, 2020]. Gastroenterology. doi: 10.1053/j.gastro.2020.08.037