Anti-TNFs for ulcerative colitis up sepsis risk after some proctocolectomies

PHOENIX – Among patients with ulcerative colitis, preoperative therapy targeting tumor necrosis factor increases the risk of postoperative complications after two-stage restorative proctocolectomy procedures but not after three-stage ones, a study has shown.

A team at the Cleveland Clinic retrospectively assessed outcomes in more than 500 patients who underwent a restorative proctocolectomy for medically refractory ulcerative colitis during a recent 5-year period. Overall, 28% were receiving an agent that targets tumor necrosis factor (TNF) before their surgery.

The main results, reported at the annual meeting of the American Society of Colon and Rectal Surgeons, showed that among patients having an initial total proctocolectomy (TPC) with ileoanal pouch–anal anastomosis, preoperative anti-TNF therapy more than doubled the risk of pelvic sepsis in the subsequent year.

In contrast, among patients having an initial subtotal colectomy (STC) with end ileostomy, preoperative anti-TNF therapy did not significantly affect the risk of complications overall, or in the subset who went on to have completion proctectomy and ileoanal pouch–anal anastomosis.

"Considering the lack of [a randomized controlled trial], our conclusion is that preoperative exposure to biologics is associated with an increased risk of pelvic sepsis after TPC with ileoanal pouch–anal anastomosis," commented lead investigator Dr. Jinyu Gu, a colorectal surgeon at the Cleveland Clinic. "This risk can be mitigated by the performance of initial STC."

The study’s senior investigator, Dr. P. Ravi Kiran, noted the importance of studying late complications in this population.

"We consciously decided to include patients who developed complications up to 1 year after surgery because quite often, these patients will not manifest their pelvic sepsis until the stoma is closed," he explained. "Some of the previous data from our institution have also shown that if someone were to get pelvic complications or septic complications that resemble Crohn’s disease, it is unlikely that it is really the disease that does it within 1 year after surgery; it is usually septic complications that manifest in a delayed fashion. ... A problem with any study that does not include patients for a prolonged follow-up is that you cannot really know what are the long-term complications because the presence of a stoma sometimes keeps the pelvic infection hidden."

"We, as colorectal surgeons, have been questioning what to do with patients who are on anti-TNF therapy when we operate on them," session comoderator Dr. Janice Rafferty, chief of the division of colon and rectal surgery at the University of Cincinnati, commented in an interview.

"I think this tells us that if we do a pouch procedure on them, and they are on anti-TNF therapy, their risk for pelvic sepsis is higher than if they had a three-stage procedure and we get them off of anti-TNF therapy," she said. "That probably supports what most colorectal surgeons suspect and want to do, but I think the gastroenterologists are currently pushing us, saying there is not a lot of evidence to say that they have a worse outcome."

Session comoderator Dr. Bruce Robb of Indiana University in Indianapolis agreed and noted that the findings support a recent shift toward multistage procedures in this population.

"For a long time, we were talking about two- versus one-stage procedures, and now we are going back, I think, especially with the advent of laparoscopy; people are much happier to do a three-stage procedure than they were even 10 years ago," he said. "This study sort of validates a change in practice pattern that’s already in place."

Dr. Gu’s team retrospectively assessed outcomes in 588 patients who underwent a restorative proctocolectomy for medically refractory ulcerative colitis between 2006 and 2010. Patients with complicated colitis, colitis-associated neoplasia, and Crohn’s disease were excluded.

The investigators assessed the rates of a variety of postoperative complications: pelvic sepsis, leaking of the colorectal stump, wound infection, postoperative hemorrhage, thromboembolism, urinary tract infection, and pneumonia.

Patients were defined as receiving anti-TNF therapy preoperatively if they had received at least 12 weeks of infliximab (Remicade) or at least 4 weeks of adalimumab (Humira) or certolizumab (Cimzia).

Of the 181 patients whose initial surgery was TPC with ileoanal pouch–anal anastomosis, 14% were receiving anti-TNF therapy preoperatively.

Within this group, the 30-day rate of complications did not differ significantly between patients who were and were not receiving preoperative anti-TNF therapy.

But the cumulative 1-year rate of pelvic sepsis was twice as high in patients receiving anti-TNF therapy (32% vs. 16%, P = .012). In adjusted analyses, these patients still had a more than doubling of the risk of pelvic sepsis (hazard ratio, 2.62; P = .027).

Of the 407 patients whose initial surgery was STC with end ileostomy, 35% were receiving anti-TNF agents preoperatively.

Within this group, patients taking anti-TNF agents preoperatively did not have an elevated risk of any of the complications studied at either 30 days or 1 year. The findings were similar among the subset who went on to have a completion proctectomy and ileoanal pouch–anal anastomosis.

Dr. Gu and Dr. Kiran both disclosed no relevant financial conflicts.

PHOENIX – Among patients with ulcerative colitis, preoperative therapy targeting tumor necrosis factor increases the risk of postoperative complications after two-stage restorative proctocolectomy procedures but not after three-stage ones, a study has shown.

A team at the Cleveland Clinic retrospectively assessed outcomes in more than 500 patients who underwent a restorative proctocolectomy for medically refractory ulcerative colitis during a recent 5-year period. Overall, 28% were receiving an agent that targets tumor necrosis factor (TNF) before their surgery.

The main results, reported at the annual meeting of the American Society of Colon and Rectal Surgeons, showed that among patients having an initial total proctocolectomy (TPC) with ileoanal pouch–anal anastomosis, preoperative anti-TNF therapy more than doubled the risk of pelvic sepsis in the subsequent year.

In contrast, among patients having an initial subtotal colectomy (STC) with end ileostomy, preoperative anti-TNF therapy did not significantly affect the risk of complications overall, or in the subset who went on to have completion proctectomy and ileoanal pouch–anal anastomosis.

"Considering the lack of [a randomized controlled trial], our conclusion is that preoperative exposure to biologics is associated with an increased risk of pelvic sepsis after TPC with ileoanal pouch–anal anastomosis," commented lead investigator Dr. Jinyu Gu, a colorectal surgeon at the Cleveland Clinic. "This risk can be mitigated by the performance of initial STC."

The study’s senior investigator, Dr. P. Ravi Kiran, noted the importance of studying late complications in this population.

"We consciously decided to include patients who developed complications up to 1 year after surgery because quite often, these patients will not manifest their pelvic sepsis until the stoma is closed," he explained. "Some of the previous data from our institution have also shown that if someone were to get pelvic complications or septic complications that resemble Crohn’s disease, it is unlikely that it is really the disease that does it within 1 year after surgery; it is usually septic complications that manifest in a delayed fashion. ... A problem with any study that does not include patients for a prolonged follow-up is that you cannot really know what are the long-term complications because the presence of a stoma sometimes keeps the pelvic infection hidden."

"We, as colorectal surgeons, have been questioning what to do with patients who are on anti-TNF therapy when we operate on them," session comoderator Dr. Janice Rafferty, chief of the division of colon and rectal surgery at the University of Cincinnati, commented in an interview.

"I think this tells us that if we do a pouch procedure on them, and they are on anti-TNF therapy, their risk for pelvic sepsis is higher than if they had a three-stage procedure and we get them off of anti-TNF therapy," she said. "That probably supports what most colorectal surgeons suspect and want to do, but I think the gastroenterologists are currently pushing us, saying there is not a lot of evidence to say that they have a worse outcome."

Session comoderator Dr. Bruce Robb of Indiana University in Indianapolis agreed and noted that the findings support a recent shift toward multistage procedures in this population.

"For a long time, we were talking about two- versus one-stage procedures, and now we are going back, I think, especially with the advent of laparoscopy; people are much happier to do a three-stage procedure than they were even 10 years ago," he said. "This study sort of validates a change in practice pattern that’s already in place."

Dr. Gu’s team retrospectively assessed outcomes in 588 patients who underwent a restorative proctocolectomy for medically refractory ulcerative colitis between 2006 and 2010. Patients with complicated colitis, colitis-associated neoplasia, and Crohn’s disease were excluded.

The investigators assessed the rates of a variety of postoperative complications: pelvic sepsis, leaking of the colorectal stump, wound infection, postoperative hemorrhage, thromboembolism, urinary tract infection, and pneumonia.

Patients were defined as receiving anti-TNF therapy preoperatively if they had received at least 12 weeks of infliximab (Remicade) or at least 4 weeks of adalimumab (Humira) or certolizumab (Cimzia).

Of the 181 patients whose initial surgery was TPC with ileoanal pouch–anal anastomosis, 14% were receiving anti-TNF therapy preoperatively.

Within this group, the 30-day rate of complications did not differ significantly between patients who were and were not receiving preoperative anti-TNF therapy.

But the cumulative 1-year rate of pelvic sepsis was twice as high in patients receiving anti-TNF therapy (32% vs. 16%, P = .012). In adjusted analyses, these patients still had a more than doubling of the risk of pelvic sepsis (hazard ratio, 2.62; P = .027).

Of the 407 patients whose initial surgery was STC with end ileostomy, 35% were receiving anti-TNF agents preoperatively.

Within this group, patients taking anti-TNF agents preoperatively did not have an elevated risk of any of the complications studied at either 30 days or 1 year. The findings were similar among the subset who went on to have a completion proctectomy and ileoanal pouch–anal anastomosis.

Dr. Gu and Dr. Kiran both disclosed no relevant financial conflicts.

PHOENIX – Among patients with ulcerative colitis, preoperative therapy targeting tumor necrosis factor increases the risk of postoperative complications after two-stage restorative proctocolectomy procedures but not after three-stage ones, a study has shown.

A team at the Cleveland Clinic retrospectively assessed outcomes in more than 500 patients who underwent a restorative proctocolectomy for medically refractory ulcerative colitis during a recent 5-year period. Overall, 28% were receiving an agent that targets tumor necrosis factor (TNF) before their surgery.

The main results, reported at the annual meeting of the American Society of Colon and Rectal Surgeons, showed that among patients having an initial total proctocolectomy (TPC) with ileoanal pouch–anal anastomosis, preoperative anti-TNF therapy more than doubled the risk of pelvic sepsis in the subsequent year.

In contrast, among patients having an initial subtotal colectomy (STC) with end ileostomy, preoperative anti-TNF therapy did not significantly affect the risk of complications overall, or in the subset who went on to have completion proctectomy and ileoanal pouch–anal anastomosis.

"Considering the lack of [a randomized controlled trial], our conclusion is that preoperative exposure to biologics is associated with an increased risk of pelvic sepsis after TPC with ileoanal pouch–anal anastomosis," commented lead investigator Dr. Jinyu Gu, a colorectal surgeon at the Cleveland Clinic. "This risk can be mitigated by the performance of initial STC."

The study’s senior investigator, Dr. P. Ravi Kiran, noted the importance of studying late complications in this population.

"We consciously decided to include patients who developed complications up to 1 year after surgery because quite often, these patients will not manifest their pelvic sepsis until the stoma is closed," he explained. "Some of the previous data from our institution have also shown that if someone were to get pelvic complications or septic complications that resemble Crohn’s disease, it is unlikely that it is really the disease that does it within 1 year after surgery; it is usually septic complications that manifest in a delayed fashion. ... A problem with any study that does not include patients for a prolonged follow-up is that you cannot really know what are the long-term complications because the presence of a stoma sometimes keeps the pelvic infection hidden."

"We, as colorectal surgeons, have been questioning what to do with patients who are on anti-TNF therapy when we operate on them," session comoderator Dr. Janice Rafferty, chief of the division of colon and rectal surgery at the University of Cincinnati, commented in an interview.

"I think this tells us that if we do a pouch procedure on them, and they are on anti-TNF therapy, their risk for pelvic sepsis is higher than if they had a three-stage procedure and we get them off of anti-TNF therapy," she said. "That probably supports what most colorectal surgeons suspect and want to do, but I think the gastroenterologists are currently pushing us, saying there is not a lot of evidence to say that they have a worse outcome."

Session comoderator Dr. Bruce Robb of Indiana University in Indianapolis agreed and noted that the findings support a recent shift toward multistage procedures in this population.

"For a long time, we were talking about two- versus one-stage procedures, and now we are going back, I think, especially with the advent of laparoscopy; people are much happier to do a three-stage procedure than they were even 10 years ago," he said. "This study sort of validates a change in practice pattern that’s already in place."

Dr. Gu’s team retrospectively assessed outcomes in 588 patients who underwent a restorative proctocolectomy for medically refractory ulcerative colitis between 2006 and 2010. Patients with complicated colitis, colitis-associated neoplasia, and Crohn’s disease were excluded.

The investigators assessed the rates of a variety of postoperative complications: pelvic sepsis, leaking of the colorectal stump, wound infection, postoperative hemorrhage, thromboembolism, urinary tract infection, and pneumonia.

Patients were defined as receiving anti-TNF therapy preoperatively if they had received at least 12 weeks of infliximab (Remicade) or at least 4 weeks of adalimumab (Humira) or certolizumab (Cimzia).

Of the 181 patients whose initial surgery was TPC with ileoanal pouch–anal anastomosis, 14% were receiving anti-TNF therapy preoperatively.

Within this group, the 30-day rate of complications did not differ significantly between patients who were and were not receiving preoperative anti-TNF therapy.

But the cumulative 1-year rate of pelvic sepsis was twice as high in patients receiving anti-TNF therapy (32% vs. 16%, P = .012). In adjusted analyses, these patients still had a more than doubling of the risk of pelvic sepsis (hazard ratio, 2.62; P = .027).

Of the 407 patients whose initial surgery was STC with end ileostomy, 35% were receiving anti-TNF agents preoperatively.

Within this group, patients taking anti-TNF agents preoperatively did not have an elevated risk of any of the complications studied at either 30 days or 1 year. The findings were similar among the subset who went on to have a completion proctectomy and ileoanal pouch–anal anastomosis.

Dr. Gu and Dr. Kiran both disclosed no relevant financial conflicts.