Researchers have developed and validated a tool to identify patients with ulcerative colitis who are most likely to achieve corticosteroid-free remission during vedolizumab therapy, according to study findings reported in Clinical Gastroenterology and Hepatology.
The investigators performed logistic regression analysis of data from GEMINI 1 Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Ulcerative Colitis; ClinicalTrials.gov Identifier: NCT00783718) of 620 patients (mean age, 40.1 ± 13; 41% women) with ulcerative colitis who underwent vedolizumab induction and maintenance therapy (derivation cohort) to identify factors associated with corticosteroid-free remission (full Mayo Score of 2 or less, no subscore greater than 1). These factors were used to develop a model to predict treatment outcomes (vedolizumab clinical decision support tool [CDST]). The study authors then evaluated the correlation between exposure and efficacy and validated the CDST in data from 199 patients (mean age, 41.5 ± 17.3; 52% women) from the VICTORY cohort who were treated with vedolizumab in the United States from May 2014 through December 2017.
The researchers found that absence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 years or more (+3 points), baseline endoscopic activity (moderate vs severe; +2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy.
Patients in the derivation and validation cohorts were then assigned to groups with low (CDST score, 26 points or less), intermediate (CDST score, 27-32 points), or high (CDST score, 33 points or more) probability of vedolizumab response. A statistically significant linear relationship was observed between the probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P < .001) in the derivation cohort.
A cutoff value of 26 points identified patients in the validation cohort who did not respond to vedolizumab with high sensitivity (93%); the low- and intermediate-probability groups benefited from reducing intervals of vedolizumab administration owing to a lack of response (P = .02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy.
“The CDST identified patients most likely to benefit from reducing intervals of vedolizumab administration due to lack of initial response,” stated the investigators.
Among several study limitations, the researchers noted that the lower bound of the confidence interval for the performance reached 0.5, suggesting that model discrimination may not be ideal. Therefore, further validation will be needed to understand external validity on additional cohorts.
“We have derived and externally validated a prediction model and CDST for achieving corticosteroid-free remission with vedolizumab in ulcerative colitis,” stated the study authors. “The vedolizumab-CDST was observed to have a high sensitivity for identifying patients with a latency of onset for response, who were less likely to achieve corticosteroid-free remission with vedolizumab and were more likely to require colectomy while on vedolizumab. Furthermore, the CDST was observed to predict treatment effectiveness with vedolizumab but not TNF antagonist therapy, confirming its drug-specific use.”
Disclosure: Some of the authors reported affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.
Dulai PS, Singh S, Vande Casteele N, et al. Development and validation of clinical scoring tool to predict outcomes of treatment with vedolizumab in patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2020;18(13):2952-2961.e8.