Meeting News

Oral vancomycin induces, maintains remission of UC in patients with UC-PSC

Alexander Dao 2019
Alexander Dao

SAN DIEGO — Oral vancomycin safely induced and maintained remission of ulcerative colitis among a subset of patients with ulcerative colitis and associated primary sclerosing cholangitis, including those who had undergone liver transplantation, according to a study presented at Digestive Disease Week.

“About half to three-quarters of patients with PSC have coexisting IBD, most of [whom] are actually patients with UC,” Alexander Dao, MD, second year resident in internal medicine at Georgetown University Hospital, said during his presentation. “The pathogenesis for both PSC and UC [is] thought to be related to an immune reaction to the gut microbiome. There are currently no consensus standard therapies for PSC at this time.”

Aline Charabaty 2019
Aline Charabaty

Dao and colleagues conducted a retrospective chart review of eight patients with UC-PSC (75% women; average age, 38 years) to determine the role of oral vancomycin in the treatment of the disease. This included patients who had no or a partial response to thiopurines and/or biologics, Aline Charabaty, MD, director of the IBD Center at Johns Hopkins School of Medicine and Sibley Memorial Hospital, told Healio Gastroenterology.

Average disease duration was 15 years and more than half of the patients (63%) had undergone liver transplantation for PSC. All patients were being treated with oral vancomycin for control of UC.

Oral vancomycin is particularly valuable for patients who are already on immunosuppressive medications after liver transplant for PSC because it does not contribute to systemic immunosuppression, according to Charabaty.

“Patients are very motivated to take an oral therapy that is effective, low-cost, easy to access, well tolerated and does not have systemic effects,” she said.

Charabaty recommended that, if a patient does not respond to mesalamine, oral vancomycin should be initiated before moving to a biologic.

The researchers calculated patients’ Total UC Mayo score and clinical, endoscopic and physician assessment subscores within 6 months before initiating oral vancomycin and within 6 to 12 months of initiating oral vancomycin. The primary endpoints were a reduction in Total Mayo score and endoscopic subscore.

Participants had an average disease duration of 15 years and many (68%) had a postliver transplant for PSC. Most patients had failed, were intolerant to or had only a partial response to mesalamine therapies (n = 7), immunomodulators (n = 5) and/or one or more biologic agents (n = 5). All participants displayed negative stool test results for Clostridium difficile prior to initiating oral vancomycin.

For the first 6 to 8 weeks of the study, participants received 125 mg oral vancomycin four times a day. Dosing was then tapered to the lowest effective dose of 125 mg oral vancomycin twice a day or three times a day. Patients were treated for up to 36 months.

Before initiating oral vancomycin, Total Mayo scores ranged from 6 to 11 and an endoscopic subscore of 2. Six to 12 months after initiating oral vancomycin, patients demonstrated a reduction in Total Mayo score of 5 to 11 points (average reduction, 7 points) and a reduction in endoscopic subscore (0 to 1).

In 9 to 36 months of follow-up, clinical and endoscopic response/remission was maintained by all patients. No side effects with oral vancomycin were noted.

“The patients in our study achieved sustained clinical remission within a few days or weeks of starting oral vancomycin and, even more importantly, achieved mucosal healing on endoscopy,” Charabaty said. “We were also able to stop the thiopurines or biologic therapy when vancomycin was started. This group represents a difficult-to-treat population, so seeing these results was very exciting and encouraging for this subgroup of patients with UC.”

This is the largest case study to date to examine oral vancomycin in patients with UC-PSC, according to Dao.

“This data suggests that we have an easy to take, affordable medication that is generally well tolerating in patients that can potentially treat both PSC and UC,” he continued.

Dao also discussed several areas where more research is needed. Randomized controlled trials will help establish the long-term efficacy and safety profile of oral vancomycin in patients with PSC-UC. In addition, researchers want to determine whether oral vancomycin is able to prevent PSC progression to cirrhosis and recurrence of PSC after liver transplant.

Finally, a standardized protocol for administering oral vancomycin is also needed, according to Dao.

“There is a lot of heterogeneity between studies in regard to oral vancomycin doses,” he said. “We need to figure out what the induction of maintenance should be for the most effective dose and length of treatment. The maintenance dose seems to be the effective way to treat these patients.” – by Alaina Tedesco

Editor’s note: This item has been updated to include length of treatment.

 

Reference:

Dao A, et al. 109. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosure: Charabaty and Dao report no relevant financial disclosures.

Alexander Dao 2019
Alexander Dao

SAN DIEGO — Oral vancomycin safely induced and maintained remission of ulcerative colitis among a subset of patients with ulcerative colitis and associated primary sclerosing cholangitis, including those who had undergone liver transplantation, according to a study presented at Digestive Disease Week.

“About half to three-quarters of patients with PSC have coexisting IBD, most of [whom] are actually patients with UC,” Alexander Dao, MD, second year resident in internal medicine at Georgetown University Hospital, said during his presentation. “The pathogenesis for both PSC and UC [is] thought to be related to an immune reaction to the gut microbiome. There are currently no consensus standard therapies for PSC at this time.”

Aline Charabaty 2019
Aline Charabaty

Dao and colleagues conducted a retrospective chart review of eight patients with UC-PSC (75% women; average age, 38 years) to determine the role of oral vancomycin in the treatment of the disease. This included patients who had no or a partial response to thiopurines and/or biologics, Aline Charabaty, MD, director of the IBD Center at Johns Hopkins School of Medicine and Sibley Memorial Hospital, told Healio Gastroenterology.

Average disease duration was 15 years and more than half of the patients (63%) had undergone liver transplantation for PSC. All patients were being treated with oral vancomycin for control of UC.

Oral vancomycin is particularly valuable for patients who are already on immunosuppressive medications after liver transplant for PSC because it does not contribute to systemic immunosuppression, according to Charabaty.

“Patients are very motivated to take an oral therapy that is effective, low-cost, easy to access, well tolerated and does not have systemic effects,” she said.

Charabaty recommended that, if a patient does not respond to mesalamine, oral vancomycin should be initiated before moving to a biologic.

The researchers calculated patients’ Total UC Mayo score and clinical, endoscopic and physician assessment subscores within 6 months before initiating oral vancomycin and within 6 to 12 months of initiating oral vancomycin. The primary endpoints were a reduction in Total Mayo score and endoscopic subscore.

Participants had an average disease duration of 15 years and many (68%) had a postliver transplant for PSC. Most patients had failed, were intolerant to or had only a partial response to mesalamine therapies (n = 7), immunomodulators (n = 5) and/or one or more biologic agents (n = 5). All participants displayed negative stool test results for Clostridium difficile prior to initiating oral vancomycin.

For the first 6 to 8 weeks of the study, participants received 125 mg oral vancomycin four times a day. Dosing was then tapered to the lowest effective dose of 125 mg oral vancomycin twice a day or three times a day. Patients were treated for up to 36 months.

Before initiating oral vancomycin, Total Mayo scores ranged from 6 to 11 and an endoscopic subscore of 2. Six to 12 months after initiating oral vancomycin, patients demonstrated a reduction in Total Mayo score of 5 to 11 points (average reduction, 7 points) and a reduction in endoscopic subscore (0 to 1).

In 9 to 36 months of follow-up, clinical and endoscopic response/remission was maintained by all patients. No side effects with oral vancomycin were noted.

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“The patients in our study achieved sustained clinical remission within a few days or weeks of starting oral vancomycin and, even more importantly, achieved mucosal healing on endoscopy,” Charabaty said. “We were also able to stop the thiopurines or biologic therapy when vancomycin was started. This group represents a difficult-to-treat population, so seeing these results was very exciting and encouraging for this subgroup of patients with UC.”

This is the largest case study to date to examine oral vancomycin in patients with UC-PSC, according to Dao.

“This data suggests that we have an easy to take, affordable medication that is generally well tolerating in patients that can potentially treat both PSC and UC,” he continued.

Dao also discussed several areas where more research is needed. Randomized controlled trials will help establish the long-term efficacy and safety profile of oral vancomycin in patients with PSC-UC. In addition, researchers want to determine whether oral vancomycin is able to prevent PSC progression to cirrhosis and recurrence of PSC after liver transplant.

Finally, a standardized protocol for administering oral vancomycin is also needed, according to Dao.

“There is a lot of heterogeneity between studies in regard to oral vancomycin doses,” he said. “We need to figure out what the induction of maintenance should be for the most effective dose and length of treatment. The maintenance dose seems to be the effective way to treat these patients.” – by Alaina Tedesco

Editor’s note: This item has been updated to include length of treatment.

 

Reference:

Dao A, et al. 109. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosure: Charabaty and Dao report no relevant financial disclosures.

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