Gastroenterology Month in Review: November 2023

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November’s Gastroenterology Month in Review features an FDA approval, the discontinuation of a phase 3 clinical program, and news about Clostridioides difficile testing and risk factors.

Although 2023 is almost over, the field of gastroenterology shows no signs of slowing down as the year comes to a close. The month of November was a busy one, characterized by an FDA approval for erosive esophagitis, the discontinuation of a phase 3 program for ulcerative colitis, and news about risks and disparities in Clostridioides difficile, all of which we spotlight in our November 2023 Gastroenterology Month in Review.

Gastroenterology FDA Decision

FDA Approves Vonoprazan to Treat Erosive Esophagitis

The FDA kicked off November with an approval on November 1, 2023, for Phathom Pharmaceuticals’ vonoprazan for the treatment of all grades of erosive esophagitis (GERD). An oral small molecule potassium-competitive acid blocker for blocking acid secretion in the stomach, vonoprazan has shown the potential to provide acid suppression for achieving pH levels important in enhancing treatment effectiveness.

The approval was based on positive results from the phase 3 PHALCON-EE study, which enrolled 1,024 patients with erosive GERD in the US and Europe and compared vonoprazan to the PPI lansoprazole in healing, maintenance of healing, and associated heartburn symptom relief. Results showed vonoprazan 20 mg met the study’s primary endpoint of non-inferiority (P < .0001) for full healing by week 8. There was a healing rate of 93%, which was greater than the 85% for 30 mg lansoprazole.

Phase 3 Clinical Trial Discontinuation

Cobitolimod Phase 3 Program Discontinued for Ulcerative Colitis Treatment

In contrast to the FDA approval of vonoprazan earlier in the month, InDex Pharmaceuticals announced the discontinuation of their phase 3 CONCLUDE program for cobitolimod in ulcerative colitis based on findings from a planned dose selection analysis conducted by an independent Data Monitoring Committee. Following the safety review and assessment for futility in Induction Study 1, the Data Monitoring Committee advised cobitolimod was unlikely to meet the primary endpoint upon completion of Induction Study 1.

The prespecified and independent analysis included the first 133 patients who had completed the 6-week induction study, accounting for approximately 30% of the total 440 patient enrollment. As part of the analysis, the Data Monitoring Committee performed a safety review and a futility assessment based on the primary endpoint clinical remission at week 6. The advice to discontinue the study was not based on safety concerns, but rather concerns regarding cobitolimod’s ability to meet the study’s primary endpoint.

News in Clostridioides difficile

Black Patients Receive Less C Diff Tests Despite Similar Positivity Rates to White Patients

Among our most popular stories in gastroenterology this month was a retrospective cohort study of inpatient Clostridioides difficile infection (CDI) testing at 3 hospitals in North Carolina. Using electronic health record data, investigators assessed racial disparities in CDI testing while controlling for disproportionate patient days between races using race-specific patient days.

Results showed White patients received the most CDI tests (21,695), followed by patients who identified as Black (11,846) and those who identified as non-White non-Black (NWNB) (1,619). The median number of CDI tests per 1,000 patient days was 13.85 (interquartile range [IQR], 9.88-16.07). Among all CDI tests, 5,225 (15%) were positive, including 3,428 from hospital A, 1,202 from hospital B, and 595 from hospital C.

White patients accounted for 3,222 (62%) positive tests, Black patients had 1,803 (35%) positive tests, and NWNB patients had 200 (4%) positive tests. Across the total surveillance period, an aggregate of 2,571,850 patient days were included: 1,499,993 patient days (58%) were attributed to White patients, 914,228 (36%) were attributed to Black patients, and 157,629 (6%) were attributed to NWNB patients.

When controlling for patient days by race, investigators noted White patients were administered more CDI tests (14.46 per 1,000 patient days) than Black patients (12.96 per 1,000 patient days; P < .0001) and NWNB patients (10.27 per 1,000 patient days; P < .0001). Further analysis revealed white patients (15%) tested positive at a greater rate than NWNB patients (12%; P = .0061) but at a similar rate to Black patients (15%; P = .3655).

Common Hospital-Administered Antibiotics Linked to C Diff, Adverse Drug Reactions

Another popular story in gastroenterology this month focused on commonly administered antibiotics and their association with risk of CDI and related adverse drug reactions. The retrospective pharmacovigilance study included CDI Individual Case Safety Reports submitted to EudraVigilance spontaneously reported as adverse drug reactions associated with the use of ceftriaxone, colistimethate, ciprofloxacin, gentamicin, linezolid, meropenem, and piperacillin/tazobactam.

A total of 119,123 adverse drug reactions were reported in EudraVigilance for the 7 antibiotics. The greatest proportions of adverse drug reactions related to CDI were observed for ciprofloxacin (31%), ceftriaxone (29%), piperacillin/tazobactam (14%), and linezolid (12%). The greatest average reports per year were for ciprofloxacin (40.5; 95% Confidence interval [CI], 27.6–53.4) and piperacillin/tazobactam (25.3; 95% CI, 13.6–36.9).

Further analysis of reports with unfavorable outcomes showed the greatest frequency of an unfavorable outcome was observed for ciprofloxacin (21.8%) and meropenem (20.5%) while the lowest frequency of an unfavorable outcome was calculated for gentamicin (11.8%) and ceftriaxone (13.2%). The greatest frequency of fatal adverse drug reactions was seen in colistimethate (15%), meropenem (14%), and ciprofloxacin (13.6%).

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