Histology more predictive of ICI colitis outcome than clinical / endoscopic measures

Tuesday, 23 Feb 2021

New findings provide an important guide to the standardised evaluation of checkpoint inhibitor-induced colitis and how to stratify therapy.

Robarts Histopathology Index [RHI] appears useful to predict which patients with immune checkpoint inhibitor (ICI) colitis will require biologic therapy and have adverse colitis outcomes, research found.

A study of 149 patients from the US, Canada and Australia compared clinical, histological and endoscopic measures of ICI colitis. Patients included those on ICI monotherapy or combination therapy for indications such as malignant melanoma and other tumours.

The study, published in AP&T, found the RHI most accurately captured the severity of ICI colitis. RHI ≥14 was the only predictor of biologic use to resolve the colitis (OR 4.3).

“Using biological use as the outcome, the optimal cut-off is RHI ≥14 with a sensitivity of 79%, specificity of 53% and a negative predictive value of 91%,” the study said.

The Index was also helpful in predicting adverse colitis outcomes including biologic-refractory colitis, colectomy or death from colitis (OR 9.5).

“The optimal cut-off for adverse colitis outcomes is RHI ≥24 with a sensitivity of 67%, specificity of 87% and a negative predictive value of 96%.”

The study said the poor correlation between symptoms and both endoscopy and histology was an important finding.

“These results indicate that symptoms do not reliably capture the severity of colonic inflammation. This is similar to inflammatory bowel disease where the disconnect between endoscopic/histological findings and symptoms is well-known.”

“For this reason, the goal of therapy in inflammatory bowel disease has shifted to more objective measures such as endoscopic and histological healing in order to reduce colonic damage and improve long-term outcomes.”

The researchers said a similar strategy may be warranted in ICI colitis.

“In summary, histological evaluation of patients with ICI colitis not only helps to establish the diagnosis but may also provide important information regarding disease course. If these results are confirmed in other cohorts, consideration should be given to including measures of histological activity in therapeutic algorithms for ICI colitis.”

An invited editorial in AP&T by Melbourne gastroenterologists Dr Andrew Buckle and Dr Britt Christensen said high-dose glucocorticoids and biological therapy such as infliximab and vedolizumab were the mainstays of treatment for ICI colitis.

“Clearly, not all patients with ICI colitis need biological therapy and it is not without risk. Identifying biomarkers to determine which patients require biological therapy is paramount,” they said.

They said the study provided an important guide to the standardised evaluation of ICI colitis and stratification of therapy.

Dr Christensen told the limbic the RHI was typically used as a research tool rather than a clinical tool.

“As with all research in ICI colitis, what remains is the need for coordinated multicentre prospective studies to test these observations and definitively determine the role of histological assessment in future therapeutic algorithms,” the editorial concluded.

The study also noted three histologically distinct patterns of ICC colitis – an acute colitis resembling infectious colitis, a chronic active colitis most like IBD, and microscopic colitis.

“The median RHI (P < 0.001), median apoptosis (P < 0.001) and proportion with increased eosinophils (P = 0.009) were significantly different across the three patterns with all being higher in the chronic active colitis pattern compared to acute colitis and microscopic colitis patterns.”

The study said it was not known if the different histological patterns of colitis responded differently to particular medical therapies.

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