Vedolizumab infection concerns diminish with growing data

PHILADELPHIA – In long-term follow-up for the treatment of inflammatory bowel disease, the novel monoclonal antibody vedolizumab continues to remain free of serious infections or other signs of major complications from altered immune function, according to pooled data presented at the annual meeting of the American College of Gastroenterology.

Over the course of follow-up, which now extends to 104 weeks in these trials, called GEMINI 1 and GEMINI 2, overall infection rates have been about the same in the vedolizumab and placebo arms even when corticosteroids or immunosuppressive agents are used concurrently, according to Dr. Edward V. Loftus Jr., professor of medicine at the Mayo Clinic, Rochester, Minn.

There is particular focus on the safety of vedolizumab, because of the theoretical risks of biologics overall and vedolizumab specifically. Vedolizumab has been shown to provide sustained remissions relative to placebo in both Crohn’s disease and ulcerative colitis in the previously presented and updated GEMINI trials, but this agent, like other biologics, alters mediators of immune function.

The follow-up summarized at the ACG meeting, which evaluated risk of adverse events of vedolizumab alone or in combination with other inflammatory bowel disease (IBD) agents that affect immune function, suggests that the risk of adverse events is low, but the conclusion is not definitive.

“There was not a signal of more side effects with combination therapy, which is reassuring. However, the study is limited by the number of adverse events available to analyze,” said Dr. David T. Rubin, section chief of gastroenterology, hepatology, and nutrition at the University of Chicago. The likelihood of a high risk of adverse events is diminishing as follow-up and patient sample size increase, but Dr. Rubin suggested that clinicians should monitor any IBD patient taking an immunosuppressive agent for infectious complications.

“At the University of Chicago IBD Center, we have now treated more than 100 patients and are studying this therapy to better understand its performance in postmarket,” Dr. Rubin said in an interview. “So far, we have made similar observations to the clinical trials and to those made by Dr. Loftus here at the ACG.”

Unlike tumor necrosis factor (TNF) inhibitors, which were the first biologics to be licensed for use in IBD, vedolizumab inhibits the migration of leukocytes in the GI tract by preventing the alpha₄beta₇ subunit from binding to the adhesion molecule MAdCAM-1. It has been unclear whether or to what degree vedolizumab shares the known risk, albeit small, of inducing opportunistic infections observed with TNF inhibitors.

The most recent data continue to suggest that there is no greater risk of infection or other complications of immune function for vedolizumab than other biologics, and the risk may be lower. In the pooled GEMINI data with 1,434 patients followed during induction and maintenance phases with data in some groups out to 104 weeks, the overall percentages of infection and the individual infections rates have been “similar,” Dr. Loftus reported.

“The exception has been nasopharyngitis, which was less common in the placebo group,” said Dr. Loftus, providing relative rates of approximately 13% and 9% for vedolizumab and placebo, respectively. He noted, however, that the length of follow-up has been longer in the vedolizumab relative to the placebo groups. Rates of tuberculosis, Clostridium difficile colitis, and other serious infections have not differed significantly.

In addition, there has been no association between vedolizumab and progressive multifocal leukoencephalopathy (PML) so far. Concern about a risk for PML was raised by the relationship of vedolizumab to natalizumab, which blocks the same adhesion compounds and has been associated with PML. The absence of PML in follow-up so far is consistent with evidence that the activity of vedolizumab, unlike the activity of natalizumab, is largely or entirely confined to the GI tract.

No multicenter, randomized trials have yet to be conducted comparing either the efficacy or safety of vedolizumab, which was approved in May 2014 for the treatment of moderate to severe Crohn’s disease and ulcerative colitis, to other biologics used in IBD.

PHILADELPHIA – In long-term follow-up for the treatment of inflammatory bowel disease, the novel monoclonal antibody vedolizumab continues to remain free of serious infections or other signs of major complications from altered immune function, according to pooled data presented at the annual meeting of the American College of Gastroenterology.

Over the course of follow-up, which now extends to 104 weeks in these trials, called GEMINI 1 and GEMINI 2, overall infection rates have been about the same in the vedolizumab and placebo arms even when corticosteroids or immunosuppressive agents are used concurrently, according to Dr. Edward V. Loftus Jr., professor of medicine at the Mayo Clinic, Rochester, Minn.

There is particular focus on the safety of vedolizumab, because of the theoretical risks of biologics overall and vedolizumab specifically. Vedolizumab has been shown to provide sustained remissions relative to placebo in both Crohn’s disease and ulcerative colitis in the previously presented and updated GEMINI trials, but this agent, like other biologics, alters mediators of immune function.

The follow-up summarized at the ACG meeting, which evaluated risk of adverse events of vedolizumab alone or in combination with other inflammatory bowel disease (IBD) agents that affect immune function, suggests that the risk of adverse events is low, but the conclusion is not definitive.

“There was not a signal of more side effects with combination therapy, which is reassuring. However, the study is limited by the number of adverse events available to analyze,” said Dr. David T. Rubin, section chief of gastroenterology, hepatology, and nutrition at the University of Chicago. The likelihood of a high risk of adverse events is diminishing as follow-up and patient sample size increase, but Dr. Rubin suggested that clinicians should monitor any IBD patient taking an immunosuppressive agent for infectious complications.

“At the University of Chicago IBD Center, we have now treated more than 100 patients and are studying this therapy to better understand its performance in postmarket,” Dr. Rubin said in an interview. “So far, we have made similar observations to the clinical trials and to those made by Dr. Loftus here at the ACG.”

Unlike tumor necrosis factor (TNF) inhibitors, which were the first biologics to be licensed for use in IBD, vedolizumab inhibits the migration of leukocytes in the GI tract by preventing the alpha₄beta₇ subunit from binding to the adhesion molecule MAdCAM-1. It has been unclear whether or to what degree vedolizumab shares the known risk, albeit small, of inducing opportunistic infections observed with TNF inhibitors.

The most recent data continue to suggest that there is no greater risk of infection or other complications of immune function for vedolizumab than other biologics, and the risk may be lower. In the pooled GEMINI data with 1,434 patients followed during induction and maintenance phases with data in some groups out to 104 weeks, the overall percentages of infection and the individual infections rates have been “similar,” Dr. Loftus reported.

“The exception has been nasopharyngitis, which was less common in the placebo group,” said Dr. Loftus, providing relative rates of approximately 13% and 9% for vedolizumab and placebo, respectively. He noted, however, that the length of follow-up has been longer in the vedolizumab relative to the placebo groups. Rates of tuberculosis, Clostridium difficile colitis, and other serious infections have not differed significantly.

In addition, there has been no association between vedolizumab and progressive multifocal leukoencephalopathy (PML) so far. Concern about a risk for PML was raised by the relationship of vedolizumab to natalizumab, which blocks the same adhesion compounds and has been associated with PML. The absence of PML in follow-up so far is consistent with evidence that the activity of vedolizumab, unlike the activity of natalizumab, is largely or entirely confined to the GI tract.

No multicenter, randomized trials have yet to be conducted comparing either the efficacy or safety of vedolizumab, which was approved in May 2014 for the treatment of moderate to severe Crohn’s disease and ulcerative colitis, to other biologics used in IBD.

PHILADELPHIA – In long-term follow-up for the treatment of inflammatory bowel disease, the novel monoclonal antibody vedolizumab continues to remain free of serious infections or other signs of major complications from altered immune function, according to pooled data presented at the annual meeting of the American College of Gastroenterology.

Over the course of follow-up, which now extends to 104 weeks in these trials, called GEMINI 1 and GEMINI 2, overall infection rates have been about the same in the vedolizumab and placebo arms even when corticosteroids or immunosuppressive agents are used concurrently, according to Dr. Edward V. Loftus Jr., professor of medicine at the Mayo Clinic, Rochester, Minn.

There is particular focus on the safety of vedolizumab, because of the theoretical risks of biologics overall and vedolizumab specifically. Vedolizumab has been shown to provide sustained remissions relative to placebo in both Crohn’s disease and ulcerative colitis in the previously presented and updated GEMINI trials, but this agent, like other biologics, alters mediators of immune function.

The follow-up summarized at the ACG meeting, which evaluated risk of adverse events of vedolizumab alone or in combination with other inflammatory bowel disease (IBD) agents that affect immune function, suggests that the risk of adverse events is low, but the conclusion is not definitive.

“There was not a signal of more side effects with combination therapy, which is reassuring. However, the study is limited by the number of adverse events available to analyze,” said Dr. David T. Rubin, section chief of gastroenterology, hepatology, and nutrition at the University of Chicago. The likelihood of a high risk of adverse events is diminishing as follow-up and patient sample size increase, but Dr. Rubin suggested that clinicians should monitor any IBD patient taking an immunosuppressive agent for infectious complications.

“At the University of Chicago IBD Center, we have now treated more than 100 patients and are studying this therapy to better understand its performance in postmarket,” Dr. Rubin said in an interview. “So far, we have made similar observations to the clinical trials and to those made by Dr. Loftus here at the ACG.”

Unlike tumor necrosis factor (TNF) inhibitors, which were the first biologics to be licensed for use in IBD, vedolizumab inhibits the migration of leukocytes in the GI tract by preventing the alpha₄beta₇ subunit from binding to the adhesion molecule MAdCAM-1. It has been unclear whether or to what degree vedolizumab shares the known risk, albeit small, of inducing opportunistic infections observed with TNF inhibitors.

The most recent data continue to suggest that there is no greater risk of infection or other complications of immune function for vedolizumab than other biologics, and the risk may be lower. In the pooled GEMINI data with 1,434 patients followed during induction and maintenance phases with data in some groups out to 104 weeks, the overall percentages of infection and the individual infections rates have been “similar,” Dr. Loftus reported.

“The exception has been nasopharyngitis, which was less common in the placebo group,” said Dr. Loftus, providing relative rates of approximately 13% and 9% for vedolizumab and placebo, respectively. He noted, however, that the length of follow-up has been longer in the vedolizumab relative to the placebo groups. Rates of tuberculosis, Clostridium difficile colitis, and other serious infections have not differed significantly.

In addition, there has been no association between vedolizumab and progressive multifocal leukoencephalopathy (PML) so far. Concern about a risk for PML was raised by the relationship of vedolizumab to natalizumab, which blocks the same adhesion compounds and has been associated with PML. The absence of PML in follow-up so far is consistent with evidence that the activity of vedolizumab, unlike the activity of natalizumab, is largely or entirely confined to the GI tract.

No multicenter, randomized trials have yet to be conducted comparing either the efficacy or safety of vedolizumab, which was approved in May 2014 for the treatment of moderate to severe Crohn’s disease and ulcerative colitis, to other biologics used in IBD.