From the AGA Journals

Tool predicted vedolizumab nonresponse in routine practice

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Tool includes variables found in clinical record

The management of moderate to severe ulcerative colitis has become more complex because of the greater number of Food and Drug–approved biologic and small-molecule agents presently available. With more options, practitioners are faced with the challenge of choosing the most appropriate agent based on disease- and patient-specific risk factors. The goals of early intervention are to achieve steroid-free remission with mucosal healing and the associated improvements in quality of life, reduced colectomy, and lower colon cancer risks.

Dr. Christina Ha, Inflammatory Bowel Center, Cedars-Sinai, Los Angeles

Dr. Christina Ha

Rather than randomly choosing among treatment options, this study by Dulai and colleagues offers a clinical prediction tool that helps clarify which option, vedolizumab versus anti–tumor necrosis factor (TNF), would be more likely, as a first-line agent, to achieve the desired steroid-free clinical remission outcome. In this tool, they included known high-risk factors for colectomy, severe endoscopic activity, and hypoalbuminemia with other variables, such as prior anti-TNF exposure and disease duration. Importantly, this information is readily accessible in a routine clinical record and, therefore, requires no additional tests or studies to calculate.

The value in these types of tools is to assist in early biologic decision-making by providing a numeric cutoff that can be used to recommend one agent versus the other. Another noted feature of this tool is the potential to identify which patients may benefit from dose optimization because lower or intermediate scores tended to respond to dose escalation in vedolizumab partial responders. However, because this tool predominantly assists with the choice of anti-TNF vs. vedolizumab, one may not be able to extrapolate these results to ustekinumab and tofacitinib positioning in ulcerative colitis. Further studies are needed to determine if these variables similarly affect steroid-free remission for these agents.

Christina Ha, MD, FACG, AGAF, is an associate professor of medicine, Inflammatory Bowel Disease Center, Cedars-Sinai, Los Angeles. She is on the advisory board of AbbVie, Janssen, Takeda, Pfizer, Salix, and InDex Pharmaceuticals; has received grant support from Pfizer; and has received research support from Pfizer and Lilly.


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

Among patients with ulcerative colitis who were treated in routine practice, a point-based clinical scoring tool predicted nonresponse to vedolizumab therapy, according to study findings published online in Clinical Gastroenterology and Hepatology.

A cutoff of 26 points or less was 93% sensitive (95% confidence interval, 79%-98%) for identifying patients who did not reach corticosteroid-free remission during 26 weeks of treatment and was 88% sensitive (95% CI, 83%-92%) for identifying patients who required colectomy, reported Parambir S. Dulai, MBBS, of the University of California, San Diego, and his associates. The tool was less reliable for predicting response to tumor necrosis factor (TNF) antagonists, indicating that it is treatment specific, they noted.

Vedolizumab, an alpha-4-beta-7 anti-integrin that restricts the migration of proinflammatory lymphocytes to the gut, can induce corticosteroid-free remissions and mucosal healing in patients with ulcerative colitis. In clinical practice, 22-week rates of clinical response and remission were approximately 51% and 30%, respectively, in a recent study. Noting the lack of real-world data on predictors of response, the researchers modeled data from 620 patients who received induction and maintenance vedolizumab during the blinded phase 3 GEMINI 1 trial. They used this model to create the clinical scoring tool, which they validated in a cohort of 322 patients with ulcerative colitis who had received vedolizumab (199 patients) or TNF antagonists (123 patients) in routine practice during the Vedolizumab for Health Outcomes in Inflammatory Bowel Diseases (VICTORY) study.

In the final multivariable model, predictors of steroid-free remission were TNF antagonist naivety, at least a 2-year history of ulcerative colitis, moderate rather than severe endoscopy activity, and baseline albumin concentration. The resulting clinical scoring tool included these four variables and multiplied them by factors ranging from 0.0647 (for baseline albumin concentration) to 0.2820 (for no prior TNF antagonist exposure). In the validation cohort, patients were categorized as “high probability” (of response) if they scored 33 points or more on the tool and “low probability” if they scored 26 points or fewer. Rates of corticosteroid-free remissions were substantially different at 32% and 12%, respectively. The tool also predicted responses to vedolizumab more accurately than it did predicted responses to TNF antagonists, indicating that it was drug specific.

In the validation cohort, 46% (10 of 22) of low- or intermediate-probability patients showed least a 50% decrease in symptom activity after their vedolizumab infusion interval was shortened to address an insufficient initial response. “However, none of the high-probability patients showed a clinical response to interval shortening,” probably because they had higher vedolizumab trough concentrations to begin with, the researchers said. They called for prospective validation of this finding, “ideally in a randomized, controlled trial setting.”

The derivation and validation cohorts differed in several important ways. The validation cohort included significantly more females, smokers, patients with moderate endoscopic disease, and patients who had failed prior TNF antagonist therapy. These patients also had a significantly higher median albumin level and a longer history of disease. “The lower bound of the confidence interval for the [model’s] performance reached 0.5, suggesting that model discrimination may not be ideal,” the researchers said. “Further validation will therefore be needed to understand external validity on additional cohorts.”

An American Gastroenterological Association Research Scholar Award supported the work. Dr. Dulai reported holding a provisional patent for the prediction model and consulting relationships and other ties to Takeda, Janssen, Pfizer, and AbbVie. His coinvestigators reported ties to numerous pharmaceutical companies.

SOURCE: Dulai PS et al. Clin Gastroenterol Hepatol. 2020 Feb 13. doi: 10.1016/j.cgh.2020.02.010.

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