Medical treatment of perianal fistulae often warranted, despite limited evidence

 

PHILADELPHIA – Perianal fistulae are a common and difficult-to-treat complication of Crohn’s disease that may often require medical therapy, though not all treatment options have robust data supporting their use in this setting, according to Mark T. Osterman, MD.

“Most studies done on fistulae actually didn’t have that as the primary endpoint – it was a secondary endpoint, so they weren’t really designed to look at fistulae, specifically,” said Dr. Osterman, associate professor of medicine in the division of gastroenterology at the University of Pennsylvania in Philadelphia.

Dr. Osterman shared his own approach to medical treatment of perianal fistulae in a presentation he gave at Digestive Diseases: New Advances, jointly provided by Rutgers and Global Academy for Medical Education.

For simple perianal fistula with no rectal inflammation, a fistulotomy is reasonable, but medical treatment may be preferable, Dr. Osterman said.

“I always favor medical therapy because it attacks the root of the problem, which is the immune system,” he explained.

Helpful treatments in this scenario include antibiotics, along with anti–tumor necrosis factor therapy with or without immunomodulators, he said.

Antibiotic use in this setting is based on uncontrolled data, and efficacy is modest at best, according to Dr. Osterman, who noted that the treatments may reduce fistula drainage but likely do not heal fistulae.

The most commonly used antibiotics are metronidazole and ciprofloxacin given for up to 2-4 months, he added.

 

Infliximab is the drug that has by far the most robust fistula data, and one of only two drugs where a fistula was the primary outcome of the studies, according to Dr. Osterman.

In a randomized trial, infliximab induction treatment more than doubled fistula-related response and remission rates, compared with placebo, he said.

Maintenance infliximab treatment likewise showed an approximate doubling of both response and remission of fistula versus placebo, he added.

While not designed to look at fistulae as a primary outcome, the randomized CHARM study of adalimumab versus placebo for maintenance of Crohn’s disease remission did demonstrate remission rates about twice as high with the use of adalimumab, compared with placebo, in 117 patients who had draining fistulae at baseline, Dr. Osterman recounted.

 

For patients with complex fistulae, as well as patients with rectal inflammation, a seton and aggressive medical therapy are likely needed, Dr. Osterman said in his presentation.

An advancement flap or medical therapies such as vedolizumab or tacrolimus might be warranted for patients who fail other medical approaches, he added.

Relevant vedolizumab data come from GEMINI 2, a large clinical trial for Crohn’s disease that included 57 patients who had draining fistulas at baseline.

“We see an improvement in remission rates with fistula with vedolizumab, compared to placebo, but again, (GEMINI 2) wasn’t designed to look at fistula, but we do use it,” said Dr. Osterman.

Tacrolimus is the only drug besides infliximab that has randomized data for fistula, according to Dr. Osterman.

 

In the small randomized study, 48 patients with Crohn’s disease and draining perianal or enterocutaneous fistulae were treated for 10 weeks with oral tacrolimus at 0.2 mg/kg per day or placebo.

Fistula improvement was seen in 43% of tacrolimus-treated patients and 8% of placebo-treated patients (P = .004), while remission was seen in 10% and 8% of those groups, respectively (P = .86), according to published data on the trial.

“[Tacrolimus] showed a nice improvement in response rates, but very similar remission rates,” Dr. Osterman said, “but it does represent an option for us, for our patients.”

Dr. Osterman reported grant/research support from UCB and serving as a consultant for AbbVie, Janssen, Lycera, Merck, Pfizer, Takeda, and UCB.

Global Academy and this news organization are owned by the same company.

 

 

PHILADELPHIA – Perianal fistulae are a common and difficult-to-treat complication of Crohn’s disease that may often require medical therapy, though not all treatment options have robust data supporting their use in this setting, according to Mark T. Osterman, MD.

“Most studies done on fistulae actually didn’t have that as the primary endpoint – it was a secondary endpoint, so they weren’t really designed to look at fistulae, specifically,” said Dr. Osterman, associate professor of medicine in the division of gastroenterology at the University of Pennsylvania in Philadelphia.

Dr. Osterman shared his own approach to medical treatment of perianal fistulae in a presentation he gave at Digestive Diseases: New Advances, jointly provided by Rutgers and Global Academy for Medical Education.

For simple perianal fistula with no rectal inflammation, a fistulotomy is reasonable, but medical treatment may be preferable, Dr. Osterman said.

“I always favor medical therapy because it attacks the root of the problem, which is the immune system,” he explained.

Helpful treatments in this scenario include antibiotics, along with anti–tumor necrosis factor therapy with or without immunomodulators, he said.

Antibiotic use in this setting is based on uncontrolled data, and efficacy is modest at best, according to Dr. Osterman, who noted that the treatments may reduce fistula drainage but likely do not heal fistulae.

The most commonly used antibiotics are metronidazole and ciprofloxacin given for up to 2-4 months, he added.

 

Infliximab is the drug that has by far the most robust fistula data, and one of only two drugs where a fistula was the primary outcome of the studies, according to Dr. Osterman.

In a randomized trial, infliximab induction treatment more than doubled fistula-related response and remission rates, compared with placebo, he said.

Maintenance infliximab treatment likewise showed an approximate doubling of both response and remission of fistula versus placebo, he added.

While not designed to look at fistulae as a primary outcome, the randomized CHARM study of adalimumab versus placebo for maintenance of Crohn’s disease remission did demonstrate remission rates about twice as high with the use of adalimumab, compared with placebo, in 117 patients who had draining fistulae at baseline, Dr. Osterman recounted.

 

For patients with complex fistulae, as well as patients with rectal inflammation, a seton and aggressive medical therapy are likely needed, Dr. Osterman said in his presentation.

An advancement flap or medical therapies such as vedolizumab or tacrolimus might be warranted for patients who fail other medical approaches, he added.

Relevant vedolizumab data come from GEMINI 2, a large clinical trial for Crohn’s disease that included 57 patients who had draining fistulas at baseline.

“We see an improvement in remission rates with fistula with vedolizumab, compared to placebo, but again, (GEMINI 2) wasn’t designed to look at fistula, but we do use it,” said Dr. Osterman.

Tacrolimus is the only drug besides infliximab that has randomized data for fistula, according to Dr. Osterman.

 

In the small randomized study, 48 patients with Crohn’s disease and draining perianal or enterocutaneous fistulae were treated for 10 weeks with oral tacrolimus at 0.2 mg/kg per day or placebo.

Fistula improvement was seen in 43% of tacrolimus-treated patients and 8% of placebo-treated patients (P = .004), while remission was seen in 10% and 8% of those groups, respectively (P = .86), according to published data on the trial.

“[Tacrolimus] showed a nice improvement in response rates, but very similar remission rates,” Dr. Osterman said, “but it does represent an option for us, for our patients.”

Dr. Osterman reported grant/research support from UCB and serving as a consultant for AbbVie, Janssen, Lycera, Merck, Pfizer, Takeda, and UCB.

Global Academy and this news organization are owned by the same company.

 

 

PHILADELPHIA – Perianal fistulae are a common and difficult-to-treat complication of Crohn’s disease that may often require medical therapy, though not all treatment options have robust data supporting their use in this setting, according to Mark T. Osterman, MD.

“Most studies done on fistulae actually didn’t have that as the primary endpoint – it was a secondary endpoint, so they weren’t really designed to look at fistulae, specifically,” said Dr. Osterman, associate professor of medicine in the division of gastroenterology at the University of Pennsylvania in Philadelphia.

Dr. Osterman shared his own approach to medical treatment of perianal fistulae in a presentation he gave at Digestive Diseases: New Advances, jointly provided by Rutgers and Global Academy for Medical Education.

For simple perianal fistula with no rectal inflammation, a fistulotomy is reasonable, but medical treatment may be preferable, Dr. Osterman said.

“I always favor medical therapy because it attacks the root of the problem, which is the immune system,” he explained.

Helpful treatments in this scenario include antibiotics, along with anti–tumor necrosis factor therapy with or without immunomodulators, he said.

Antibiotic use in this setting is based on uncontrolled data, and efficacy is modest at best, according to Dr. Osterman, who noted that the treatments may reduce fistula drainage but likely do not heal fistulae.

The most commonly used antibiotics are metronidazole and ciprofloxacin given for up to 2-4 months, he added.

 

Infliximab is the drug that has by far the most robust fistula data, and one of only two drugs where a fistula was the primary outcome of the studies, according to Dr. Osterman.

In a randomized trial, infliximab induction treatment more than doubled fistula-related response and remission rates, compared with placebo, he said.

Maintenance infliximab treatment likewise showed an approximate doubling of both response and remission of fistula versus placebo, he added.

While not designed to look at fistulae as a primary outcome, the randomized CHARM study of adalimumab versus placebo for maintenance of Crohn’s disease remission did demonstrate remission rates about twice as high with the use of adalimumab, compared with placebo, in 117 patients who had draining fistulae at baseline, Dr. Osterman recounted.

 

For patients with complex fistulae, as well as patients with rectal inflammation, a seton and aggressive medical therapy are likely needed, Dr. Osterman said in his presentation.

An advancement flap or medical therapies such as vedolizumab or tacrolimus might be warranted for patients who fail other medical approaches, he added.

Relevant vedolizumab data come from GEMINI 2, a large clinical trial for Crohn’s disease that included 57 patients who had draining fistulas at baseline.

“We see an improvement in remission rates with fistula with vedolizumab, compared to placebo, but again, (GEMINI 2) wasn’t designed to look at fistula, but we do use it,” said Dr. Osterman.

Tacrolimus is the only drug besides infliximab that has randomized data for fistula, according to Dr. Osterman.

 

In the small randomized study, 48 patients with Crohn’s disease and draining perianal or enterocutaneous fistulae were treated for 10 weeks with oral tacrolimus at 0.2 mg/kg per day or placebo.

Fistula improvement was seen in 43% of tacrolimus-treated patients and 8% of placebo-treated patients (P = .004), while remission was seen in 10% and 8% of those groups, respectively (P = .86), according to published data on the trial.

“[Tacrolimus] showed a nice improvement in response rates, but very similar remission rates,” Dr. Osterman said, “but it does represent an option for us, for our patients.”

Dr. Osterman reported grant/research support from UCB and serving as a consultant for AbbVie, Janssen, Lycera, Merck, Pfizer, Takeda, and UCB.

Global Academy and this news organization are owned by the same company.