2015 Advances In IBD

ORLANDO – You can confidently treat mild to severe Clostridium difficile infection in patients with inflammatory bowel disease (IBD) without disrupting their immunosuppression or other treatments, according to an expert.

“If your patient with IBD needs a fecal transplant for C. diff., you should not be concerned about withholding it,” Dr. Alan C. Moss, AGAF, said during a basic science presentation at a conference on IBD, sponsored by the Crohn’s and Colitis Foundation of America. Dr. Moss is associate professor of medicine and the director of translational research at Harvard Medical School, Boston.

The first step, after you’ve determined that your patient has a C. diff. infection, as opposed to having been only colonized by the bacterium, is choosing the best antibiotic. “Unfortunately, almost all IBD patients are excluded from controlled trials of antibiotics in C. diff. infection, so all we really have to go on are retrospective cohort data,” he said.One such study, uncontrolled for disease severity, showed that a third of 114 inpatients with IBD who had a co-occurring C. diff. infection had higher 30-day readmission rates when treated first with metronidazole, per current standards of care, compared with the remaining two-thirds of patients who were treated first with vancomycin. The metronidazole group also averaged double the length of stays of the vancomycin group (Antimicrob Agents Chemother. 2014 Sep;58:5054-9 [doi: 10.1128/AAC.02606-13]).“This suggests that in IBD patients, especially for those who meet criteria for a severe C. diff. infection, vancomycin is the way to go,” Dr. Moss said, noting a trend of metronidazole for mild infections in this cohort having ever less efficacy.

Beyond mild infection, the first line of treatment should be vancomycin 125 mg four times daily, or 500 mg four times daily if it is complicated disease, he said. If your patient has recurrent C. diff. infection, Dr. Moss recommends a prolonged taper of vancomycin, and vigilance to be sure it’s truly an infection and not a flare-up of colonized bacteria.

“My bar for doing fecal transplant in these patients has dropped considerably in the last few years, because if you really want to squeeze out the niche that C. diff. occupies in the microbiome, fecal transplant is really the most effective way we have of doing that,” Dr. Moss said.

While there is a division in the field over whether to continue immunosuppression during antibiotic treatment, Dr. Moss cited a small study indicating that patients who were on two or more immunosuppressants had a higher risk of death, megacolon, or shock during C. diff. treatment. “It’s hard to draw many conclusions from that,” he said. “It may just be a surrogate marker of severity of disease rather than infection, per se.”

The standard of care for recurrent and refractory C. diff. infection is fecal transplant, Dr. Moss said. A study showed an 89% cure rate of C. diff. infection after a single fecal transplant in IBD patients. Of the 36 IBD patients in the study, half of whom were on biologic and immunosuppressive therapies, 4 had disease flare-ups (Am J Gastroenterol. 2014 Jul;109:1065-71; N Engl J Med. 2013 Jan 31;368:474-5). As for determining if there is an actual infection rather than colonization of C. diff., Dr. Moss said switching from using ELISA (enzyme-linked immunoassay) to PCR (polymerase chain reaction) testing was helpful in first-time infections because the latter is more sensitive for determining actual infection. However, if a patient has recurrent infection, the higher clinical specificity of PCR makes it harder to tell if a positive result is infection or simply colonization. Some institutions have dropped ELISA testing altogether, but the use of single-molecule array testing is, with its exponential sensitivity, a “good half-way step” between ELISA and PCR, and is useful for determining who is colonized vs. who is actually producing the toxin, even at a very low level, Dr Moss said.

Dr. Moss disclosed he has consulted for Janssen, Theravance, and Seres, and has received research support from the National Institute for Diabetes, Digestive, and Kidney Diseases, and Helmsley.

[email protected]
On Twitter @whitneymcknight

ORLANDO – You can confidently treat mild to severe Clostridium difficile infection in patients with inflammatory bowel disease (IBD) without disrupting their immunosuppression or other treatments, according to an expert.

“If your patient with IBD needs a fecal transplant for C. diff., you should not be concerned about withholding it,” Dr. Alan C. Moss, AGAF, said during a basic science presentation at a conference on IBD, sponsored by the Crohn’s and Colitis Foundation of America. Dr. Moss is associate professor of medicine and the director of translational research at Harvard Medical School, Boston.

The first step, after you’ve determined that your patient has a C. diff. infection, as opposed to having been only colonized by the bacterium, is choosing the best antibiotic. “Unfortunately, almost all IBD patients are excluded from controlled trials of antibiotics in C. diff. infection, so all we really have to go on are retrospective cohort data,” he said.One such study, uncontrolled for disease severity, showed that a third of 114 inpatients with IBD who had a co-occurring C. diff. infection had higher 30-day readmission rates when treated first with metronidazole, per current standards of care, compared with the remaining two-thirds of patients who were treated first with vancomycin. The metronidazole group also averaged double the length of stays of the vancomycin group (Antimicrob Agents Chemother. 2014 Sep;58:5054-9 [doi: 10.1128/AAC.02606-13]).“This suggests that in IBD patients, especially for those who meet criteria for a severe C. diff. infection, vancomycin is the way to go,” Dr. Moss said, noting a trend of metronidazole for mild infections in this cohort having ever less efficacy.

Beyond mild infection, the first line of treatment should be vancomycin 125 mg four times daily, or 500 mg four times daily if it is complicated disease, he said. If your patient has recurrent C. diff. infection, Dr. Moss recommends a prolonged taper of vancomycin, and vigilance to be sure it’s truly an infection and not a flare-up of colonized bacteria.

“My bar for doing fecal transplant in these patients has dropped considerably in the last few years, because if you really want to squeeze out the niche that C. diff. occupies in the microbiome, fecal transplant is really the most effective way we have of doing that,” Dr. Moss said.

While there is a division in the field over whether to continue immunosuppression during antibiotic treatment, Dr. Moss cited a small study indicating that patients who were on two or more immunosuppressants had a higher risk of death, megacolon, or shock during C. diff. treatment. “It’s hard to draw many conclusions from that,” he said. “It may just be a surrogate marker of severity of disease rather than infection, per se.”

The standard of care for recurrent and refractory C. diff. infection is fecal transplant, Dr. Moss said. A study showed an 89% cure rate of C. diff. infection after a single fecal transplant in IBD patients. Of the 36 IBD patients in the study, half of whom were on biologic and immunosuppressive therapies, 4 had disease flare-ups (Am J Gastroenterol. 2014 Jul;109:1065-71; N Engl J Med. 2013 Jan 31;368:474-5). As for determining if there is an actual infection rather than colonization of C. diff., Dr. Moss said switching from using ELISA (enzyme-linked immunoassay) to PCR (polymerase chain reaction) testing was helpful in first-time infections because the latter is more sensitive for determining actual infection. However, if a patient has recurrent infection, the higher clinical specificity of PCR makes it harder to tell if a positive result is infection or simply colonization. Some institutions have dropped ELISA testing altogether, but the use of single-molecule array testing is, with its exponential sensitivity, a “good half-way step” between ELISA and PCR, and is useful for determining who is colonized vs. who is actually producing the toxin, even at a very low level, Dr Moss said.

Dr. Moss disclosed he has consulted for Janssen, Theravance, and Seres, and has received research support from the National Institute for Diabetes, Digestive, and Kidney Diseases, and Helmsley.

[email protected]
On Twitter @whitneymcknight

ORLANDO – You can confidently treat mild to severe Clostridium difficile infection in patients with inflammatory bowel disease (IBD) without disrupting their immunosuppression or other treatments, according to an expert.

“If your patient with IBD needs a fecal transplant for C. diff., you should not be concerned about withholding it,” Dr. Alan C. Moss, AGAF, said during a basic science presentation at a conference on IBD, sponsored by the Crohn’s and Colitis Foundation of America. Dr. Moss is associate professor of medicine and the director of translational research at Harvard Medical School, Boston.

The first step, after you’ve determined that your patient has a C. diff. infection, as opposed to having been only colonized by the bacterium, is choosing the best antibiotic. “Unfortunately, almost all IBD patients are excluded from controlled trials of antibiotics in C. diff. infection, so all we really have to go on are retrospective cohort data,” he said.One such study, uncontrolled for disease severity, showed that a third of 114 inpatients with IBD who had a co-occurring C. diff. infection had higher 30-day readmission rates when treated first with metronidazole, per current standards of care, compared with the remaining two-thirds of patients who were treated first with vancomycin. The metronidazole group also averaged double the length of stays of the vancomycin group (Antimicrob Agents Chemother. 2014 Sep;58:5054-9 [doi: 10.1128/AAC.02606-13]).“This suggests that in IBD patients, especially for those who meet criteria for a severe C. diff. infection, vancomycin is the way to go,” Dr. Moss said, noting a trend of metronidazole for mild infections in this cohort having ever less efficacy.

Beyond mild infection, the first line of treatment should be vancomycin 125 mg four times daily, or 500 mg four times daily if it is complicated disease, he said. If your patient has recurrent C. diff. infection, Dr. Moss recommends a prolonged taper of vancomycin, and vigilance to be sure it’s truly an infection and not a flare-up of colonized bacteria.

“My bar for doing fecal transplant in these patients has dropped considerably in the last few years, because if you really want to squeeze out the niche that C. diff. occupies in the microbiome, fecal transplant is really the most effective way we have of doing that,” Dr. Moss said.

While there is a division in the field over whether to continue immunosuppression during antibiotic treatment, Dr. Moss cited a small study indicating that patients who were on two or more immunosuppressants had a higher risk of death, megacolon, or shock during C. diff. treatment. “It’s hard to draw many conclusions from that,” he said. “It may just be a surrogate marker of severity of disease rather than infection, per se.”

The standard of care for recurrent and refractory C. diff. infection is fecal transplant, Dr. Moss said. A study showed an 89% cure rate of C. diff. infection after a single fecal transplant in IBD patients. Of the 36 IBD patients in the study, half of whom were on biologic and immunosuppressive therapies, 4 had disease flare-ups (Am J Gastroenterol. 2014 Jul;109:1065-71; N Engl J Med. 2013 Jan 31;368:474-5). As for determining if there is an actual infection rather than colonization of C. diff., Dr. Moss said switching from using ELISA (enzyme-linked immunoassay) to PCR (polymerase chain reaction) testing was helpful in first-time infections because the latter is more sensitive for determining actual infection. However, if a patient has recurrent infection, the higher clinical specificity of PCR makes it harder to tell if a positive result is infection or simply colonization. Some institutions have dropped ELISA testing altogether, but the use of single-molecule array testing is, with its exponential sensitivity, a “good half-way step” between ELISA and PCR, and is useful for determining who is colonized vs. who is actually producing the toxin, even at a very low level, Dr Moss said.

Dr. Moss disclosed he has consulted for Janssen, Theravance, and Seres, and has received research support from the National Institute for Diabetes, Digestive, and Kidney Diseases, and Helmsley.

[email protected]
On Twitter @whitneymcknight

ORLANDO – A range of novel therapies are set to come online for the treatment of inflammatory bowel disease (IBD), but they will miss the mark when it comes to meeting the need for better, longer-lasting outcomes, according to one expert.

“We’re positioning our therapies all wrong,” Dr. Stephen Hanauer said at a conference on inflammatory bowel diseases sponsored by the Crohn’s and Colitis Foundation of America.

“In psoriasis, patients are immediately given effective treatment with ustekinumab, but in IBD, we have to wait for patients to fail multiple therapies before they are given an effective one,” said Dr. Hanauer, who is the Clifford Joseph Barborka Professor of Medicine in the division of gastroenterology and hepatology at Northwestern University, Chicago. The result, he said, is that after first-line therapies in IBD have been used to diminishing effect, patients typically have waited up to between 6 and 10 years before they are given the treatment that works best for them. By then, when a patient likely has experienced penetrating disease and fistulas, even the most effective therapy has less than a 50% chance of working well.

This upside down state of affairs in the field is due to a combination of factors. Since the 1998 introduction to the U.S. market of infliximab for treating Crohn’s disease, much has been learned about the characteristics of IBD, including that it is a chronic, progressive condition with a higher burden of inflammation than is necessarily indicated by clinical symptoms.

But at the time infliximab was introduced, it was viewed not as a first-line treatment that could prevent further disease, but as a last ditch effort to halt an already rampant disease state that typically had its roots of destruction well planted long before the patient presented clinically, according to Dr. Hanauer.

In the last 2 decades, however, numerous studies have shown that earlier intervention with biologics results in higher treatment response rates and less structural trauma. []

In addition, data indicate that administering the correct choice of anti–tumor necrosis factor (TNF) agent in biologic-naive patients will yield as much as a 20% greater response rate, which could lead to lower costs. “Long-term pharmacoeconomic data are needed to include not only direct costs of care, but also indirect costs that capture lost income, productivity, [and] disability,” Dr. Hanauer said in an interview.

As it stands now, even vedolizumab, indicated in 2014 for use in both Crohn’s disease and ulcerative colitis, is kept for an even later stage of disease in the standard algorithm, coming behind not only “severe stage of disease” but placed after a patient has failed other anti-TNF treatment.

Biologics are far safer than the corticosteroids, which precede them in the typical treatment algorithm, but because cost is king, according Dr. Hanauer, “it’s the cost that drives our later-stage intervention … if anti-TNFs cost a dollar, we’d use them in everything.”

“We would see more impact if we move these therapies earlier into treatment,” he said. “Now we give the patients least likely to respond to these treatments, the [costliest] therapies,” Dr. Hanauer said during his presentation.

Meanwhile, the several novel IBD therapies in development are primarily being tested for late-stage disease. Changing the criteria for inclusion in such clinical trials could mean future treatment is more cost effective. “Study sponsors could go after ‘earlier’ indications in the mild to moderate range,” he said in the interview.

To improve the treatment algorithms already in use, Dr. Hanauer said clinicians should learn more about the pharmacokinetics and pharmacodynamics of their armamentarium, something he said most clinical trials tend to ignore. “Most [IBD] drugs were developed for rheumatoid arthritis where these kinds of considerations are not as important since they have many more ‘tools’ [to choose from] in rheumatology. In IBD, we have had to make the best of our limited tools. Industry would prefer to keep things simple, but it isn’t.”

Also availing themselves of therapeutic drug monitoring would help clinicians ensure that patients have high enough blood levels of their treatment at the time they complete induction therapy, making the management phase easier, Dr. Hanauer said.

Redefining disease severity will mean that new treatments will have more efficacy, and can lead to more opportunities for novel treatments to work. Until then, leaving biologics to be the agent of last resort means, according to Dr. Hanauer, there are more patients “who have none of the benefit and all of the risk.”

Dr. Hanauer reported several relevant financial disclosures, including AbbVie, Actavis, Hospira, Janssen, Novo Nordisk, and Pfizer.

Potential new inflammatory bowel disease treatments

Adhesion molecule–based therapies
• PF-00547659 (Pfizer), an anti-MAdCam S1P1 agonist; an oral agent; for ulcerative colitis
• Ozanimod (Celgene); for ulcerative colitis; now in phase III
• Etrolizumab (Hoffmann-La Roche); for Crohn’s disease; now in phase III

Biologics for IL-12/23 pathways
MEDI2070 (MedImmune/Amgen), an anti-p19 antibody; targets IL-23 for Crohn’s disease

Agents for the JAK-STAT pathway
• Mongersen (Celgene), an oral SMAD7 antisense oligonucleotide; for Crohn’s disease; in phase III
• Tofacitinib (Pfizer)

Sources: Dr. Brian Feagan, University of Western Ontario; Dr. Bruce Sands, Mount Sinai School of Medicine; Dr. Bill Sandborn, University of California, San Diego

[email protected]

On Twitter @whitneymcknight

ORLANDO – A range of novel therapies are set to come online for the treatment of inflammatory bowel disease (IBD), but they will miss the mark when it comes to meeting the need for better, longer-lasting outcomes, according to one expert.

“We’re positioning our therapies all wrong,” Dr. Stephen Hanauer said at a conference on inflammatory bowel diseases sponsored by the Crohn’s and Colitis Foundation of America.

“In psoriasis, patients are immediately given effective treatment with ustekinumab, but in IBD, we have to wait for patients to fail multiple therapies before they are given an effective one,” said Dr. Hanauer, who is the Clifford Joseph Barborka Professor of Medicine in the division of gastroenterology and hepatology at Northwestern University, Chicago. The result, he said, is that after first-line therapies in IBD have been used to diminishing effect, patients typically have waited up to between 6 and 10 years before they are given the treatment that works best for them. By then, when a patient likely has experienced penetrating disease and fistulas, even the most effective therapy has less than a 50% chance of working well.

This upside down state of affairs in the field is due to a combination of factors. Since the 1998 introduction to the U.S. market of infliximab for treating Crohn’s disease, much has been learned about the characteristics of IBD, including that it is a chronic, progressive condition with a higher burden of inflammation than is necessarily indicated by clinical symptoms.

But at the time infliximab was introduced, it was viewed not as a first-line treatment that could prevent further disease, but as a last ditch effort to halt an already rampant disease state that typically had its roots of destruction well planted long before the patient presented clinically, according to Dr. Hanauer.

In the last 2 decades, however, numerous studies have shown that earlier intervention with biologics results in higher treatment response rates and less structural trauma. []

In addition, data indicate that administering the correct choice of anti–tumor necrosis factor (TNF) agent in biologic-naive patients will yield as much as a 20% greater response rate, which could lead to lower costs. “Long-term pharmacoeconomic data are needed to include not only direct costs of care, but also indirect costs that capture lost income, productivity, [and] disability,” Dr. Hanauer said in an interview.

As it stands now, even vedolizumab, indicated in 2014 for use in both Crohn’s disease and ulcerative colitis, is kept for an even later stage of disease in the standard algorithm, coming behind not only “severe stage of disease” but placed after a patient has failed other anti-TNF treatment.

Biologics are far safer than the corticosteroids, which precede them in the typical treatment algorithm, but because cost is king, according Dr. Hanauer, “it’s the cost that drives our later-stage intervention … if anti-TNFs cost a dollar, we’d use them in everything.”

“We would see more impact if we move these therapies earlier into treatment,” he said. “Now we give the patients least likely to respond to these treatments, the [costliest] therapies,” Dr. Hanauer said during his presentation.

Meanwhile, the several novel IBD therapies in development are primarily being tested for late-stage disease. Changing the criteria for inclusion in such clinical trials could mean future treatment is more cost effective. “Study sponsors could go after ‘earlier’ indications in the mild to moderate range,” he said in the interview.

To improve the treatment algorithms already in use, Dr. Hanauer said clinicians should learn more about the pharmacokinetics and pharmacodynamics of their armamentarium, something he said most clinical trials tend to ignore. “Most [IBD] drugs were developed for rheumatoid arthritis where these kinds of considerations are not as important since they have many more ‘tools’ [to choose from] in rheumatology. In IBD, we have had to make the best of our limited tools. Industry would prefer to keep things simple, but it isn’t.”

Also availing themselves of therapeutic drug monitoring would help clinicians ensure that patients have high enough blood levels of their treatment at the time they complete induction therapy, making the management phase easier, Dr. Hanauer said.

Redefining disease severity will mean that new treatments will have more efficacy, and can lead to more opportunities for novel treatments to work. Until then, leaving biologics to be the agent of last resort means, according to Dr. Hanauer, there are more patients “who have none of the benefit and all of the risk.”

Dr. Hanauer reported several relevant financial disclosures, including AbbVie, Actavis, Hospira, Janssen, Novo Nordisk, and Pfizer.

Potential new inflammatory bowel disease treatments

Adhesion molecule–based therapies
• PF-00547659 (Pfizer), an anti-MAdCam S1P1 agonist; an oral agent; for ulcerative colitis
• Ozanimod (Celgene); for ulcerative colitis; now in phase III
• Etrolizumab (Hoffmann-La Roche); for Crohn’s disease; now in phase III

Biologics for IL-12/23 pathways
MEDI2070 (MedImmune/Amgen), an anti-p19 antibody; targets IL-23 for Crohn’s disease

Agents for the JAK-STAT pathway
• Mongersen (Celgene), an oral SMAD7 antisense oligonucleotide; for Crohn’s disease; in phase III
• Tofacitinib (Pfizer)

Sources: Dr. Brian Feagan, University of Western Ontario; Dr. Bruce Sands, Mount Sinai School of Medicine; Dr. Bill Sandborn, University of California, San Diego

[email protected]

On Twitter @whitneymcknight

ORLANDO – A range of novel therapies are set to come online for the treatment of inflammatory bowel disease (IBD), but they will miss the mark when it comes to meeting the need for better, longer-lasting outcomes, according to one expert.

“We’re positioning our therapies all wrong,” Dr. Stephen Hanauer said at a conference on inflammatory bowel diseases sponsored by the Crohn’s and Colitis Foundation of America.

“In psoriasis, patients are immediately given effective treatment with ustekinumab, but in IBD, we have to wait for patients to fail multiple therapies before they are given an effective one,” said Dr. Hanauer, who is the Clifford Joseph Barborka Professor of Medicine in the division of gastroenterology and hepatology at Northwestern University, Chicago. The result, he said, is that after first-line therapies in IBD have been used to diminishing effect, patients typically have waited up to between 6 and 10 years before they are given the treatment that works best for them. By then, when a patient likely has experienced penetrating disease and fistulas, even the most effective therapy has less than a 50% chance of working well.

This upside down state of affairs in the field is due to a combination of factors. Since the 1998 introduction to the U.S. market of infliximab for treating Crohn’s disease, much has been learned about the characteristics of IBD, including that it is a chronic, progressive condition with a higher burden of inflammation than is necessarily indicated by clinical symptoms.

But at the time infliximab was introduced, it was viewed not as a first-line treatment that could prevent further disease, but as a last ditch effort to halt an already rampant disease state that typically had its roots of destruction well planted long before the patient presented clinically, according to Dr. Hanauer.

In the last 2 decades, however, numerous studies have shown that earlier intervention with biologics results in higher treatment response rates and less structural trauma. []

In addition, data indicate that administering the correct choice of anti–tumor necrosis factor (TNF) agent in biologic-naive patients will yield as much as a 20% greater response rate, which could lead to lower costs. “Long-term pharmacoeconomic data are needed to include not only direct costs of care, but also indirect costs that capture lost income, productivity, [and] disability,” Dr. Hanauer said in an interview.

As it stands now, even vedolizumab, indicated in 2014 for use in both Crohn’s disease and ulcerative colitis, is kept for an even later stage of disease in the standard algorithm, coming behind not only “severe stage of disease” but placed after a patient has failed other anti-TNF treatment.

Biologics are far safer than the corticosteroids, which precede them in the typical treatment algorithm, but because cost is king, according Dr. Hanauer, “it’s the cost that drives our later-stage intervention … if anti-TNFs cost a dollar, we’d use them in everything.”

“We would see more impact if we move these therapies earlier into treatment,” he said. “Now we give the patients least likely to respond to these treatments, the [costliest] therapies,” Dr. Hanauer said during his presentation.

Meanwhile, the several novel IBD therapies in development are primarily being tested for late-stage disease. Changing the criteria for inclusion in such clinical trials could mean future treatment is more cost effective. “Study sponsors could go after ‘earlier’ indications in the mild to moderate range,” he said in the interview.

To improve the treatment algorithms already in use, Dr. Hanauer said clinicians should learn more about the pharmacokinetics and pharmacodynamics of their armamentarium, something he said most clinical trials tend to ignore. “Most [IBD] drugs were developed for rheumatoid arthritis where these kinds of considerations are not as important since they have many more ‘tools’ [to choose from] in rheumatology. In IBD, we have had to make the best of our limited tools. Industry would prefer to keep things simple, but it isn’t.”

Also availing themselves of therapeutic drug monitoring would help clinicians ensure that patients have high enough blood levels of their treatment at the time they complete induction therapy, making the management phase easier, Dr. Hanauer said.

Redefining disease severity will mean that new treatments will have more efficacy, and can lead to more opportunities for novel treatments to work. Until then, leaving biologics to be the agent of last resort means, according to Dr. Hanauer, there are more patients “who have none of the benefit and all of the risk.”

Dr. Hanauer reported several relevant financial disclosures, including AbbVie, Actavis, Hospira, Janssen, Novo Nordisk, and Pfizer.

Potential new inflammatory bowel disease treatments

Adhesion molecule–based therapies
• PF-00547659 (Pfizer), an anti-MAdCam S1P1 agonist; an oral agent; for ulcerative colitis
• Ozanimod (Celgene); for ulcerative colitis; now in phase III
• Etrolizumab (Hoffmann-La Roche); for Crohn’s disease; now in phase III

Biologics for IL-12/23 pathways
MEDI2070 (MedImmune/Amgen), an anti-p19 antibody; targets IL-23 for Crohn’s disease

Agents for the JAK-STAT pathway
• Mongersen (Celgene), an oral SMAD7 antisense oligonucleotide; for Crohn’s disease; in phase III
• Tofacitinib (Pfizer)

Sources: Dr. Brian Feagan, University of Western Ontario; Dr. Bruce Sands, Mount Sinai School of Medicine; Dr. Bill Sandborn, University of California, San Diego

[email protected]

On Twitter @whitneymcknight

ORLANDO – To delay or prevent recurrence of Crohn’s disease in patients after they’ve undergone ileocolonic resectioning, the ultimate question is where the “sweet spot” is for timing biologic therapy.

“In 2016, symptoms will still guide treatment,” said Dr. Miguel D. Regueiro, professor of medicine at the University of Pittsburgh and clinical medical director of the University’s IBD Center, during the clinical track of this year’s annual Advances in Inflammatory Bowel Diseases meeting, sponsored by the Crohn’s and Colitis Foundation of America. But when it comes to the exact timing of administering anti–tumor necrosis factor (TNF) agents, clinicians should look to risk factors for recurrence.

Whitney McKnight/Frontline Medical News

The notion that immediate treatment with a biologic after surgical resectioning is best is supported by phase III data from the international, multicenter PREVENT trial, for which Dr. Regueiro was principal investigator. It demonstrated that at week 79 and week 104, immediate treatment with the biologic infliximab 5 mg/kg every 8 weeks postsurgery in patients with high risk for recurrence (smokers, those with penetrating or fistulizing disease, or a history of resectioning) resulted in lower but not statistically significant rates of the composite endpoint of clinical recurrence and endoscopic scores greater than 2, when compared with placebo (P = .097 at 76 weeks and P = .098 at 104 weeks).

Dr. Regueiro noted in an interview that often, even though endoscopic recurrence scores might be high, following surgery, patients are in clinical remission and so do not report any symptoms. He noted that when only endoscopic outcomes prior to or at week 76 in the PREVENT trial were analyzed as the secondary endpoint, there was a statistically significant difference when compared with placebo: The 147 randomly assigned study arm participants had a recurrence rate of 22.4% vs. 51.3% in 150 controls (P less than .001). Further, Rutgeerts scores equal or greater than i-3 occurred in 83.1% of participants in the placebo group, compared with 28.4% in the infliximab group at week 76.

“The take-home message is that surgery induces a deep remission where patient’s ‘feel well’ and by using a clinical symptom score we do not detect recurrence, probably for years,” Dr. Regueiro said in the interview.

What about waiting to offer treatment?

Results from the POCER trial, also conducted internationally at a number of centers, support this approach.

In the trial, 174 postoperative patients at high risk for recurrence were randomly assigned in a 2:1 ratio to either standard care – colonoscopy at 18 months – or to receive a colonoscopy at 6 months, followed by medication if there was an endoscopic recurrence of i-2 or greater.

Both study arms were given metronidazole 400 mg twice a day for 3 months. If patients were intolerant, the dose was reduced to 200 mg twice daily or was stopped altogether. If they were high risk but medication naive, patients were given azathioprine 2 mg/kg or 6-mercaptopurine 1.5 mg/kg once daily, beginning within 1 month after surgery. Patients intolerant to this regime were administered adalimumab 160/80/40 mg accordingly, every other week.

At 18 months, those patients who’d been observed endoscopically at 6 months and given medication if necessary had a 49% rate of recurrence compared with 67% in the group given standard care, a statistically significant difference.

However, when Dr. Regueiro, who was not directly involved with the POCER trial, conducted an informal review of the data, he found that patients who’d been on thiopurines had an endoscopic recurrence rate at 6 months of 45% vs. the 21% rate in the adalimumab patients. “This means that waiting on anti-TNF and giving thiopurine meant nearly half the patients had recurrence in 6 months, compared with anti-TNF treated patients.”

So then, when should biologics enter the treatment picture?

Again, look to the risk profile, said Dr. Regueiro. Patients who are 30 years of age or younger, have ileocolonic disease, smoke, have penetrating disease, or have already had two or more surgeries or had a short duration between time of diagnosis and surgery are considered at high risk for return of the disease.

In his own practice, Dr. Regueiro said he puts all but the low-risk patients on some form of immediate postoperative medication. Patients at moderate risk, such as those who have had a resection within 10 years of diagnosis, receive 6-mercaptopurine or azathioprine plus metronidazole (if tolerated) and are given colonoscopy at 6-12 months postoperatively. If there is a recurrence at that point, then he will start the patient on an anti-TNF. If not, then he sees them again in 1-3 years for a colonoscopy. Dr. Regueiro treats patients at high risk for recurrence more frequently with combination therapies, immediately setting them on a regimen of anti-TNF plus immunosuppressive therapy followed by a 6-12 month postoperative colonoscopy after which he adjusts treatment if there is active disease, including increasing the dose of the biologic or switching to another one.

But just what length of time actually constitutes “immediately after surgery?” In the PREVENT trial, clinicians had up to 45 days to begin therapy, although Dr. Regueiro said he prefers to start between 2 and 4 weeks postsurgery, a number with which panel moderator Dr. David T. Rubin, codirector of the University of Chicago Digestive Diseases Center, agreed.

While these study results help pinpoint the range for when to use biologics, Dr. Regueiro said in the interview, “Future study is need to determine the ‘tipping point’ where postoperative Crohn’s disease recurrence results in significant bowel damage and renders medications ineffective. Finding the ‘biologic sweet spot’ of when to start aggressive therapy versus a ‘wait and watch’ approach remains the question.”

Dr. Regueiro disclosed he is a consultant for AbbVie, Janssen, UCB, Pfizer, and Takeda.

[email protected]

On Twitter @whitneymcknight

ORLANDO – To delay or prevent recurrence of Crohn’s disease in patients after they’ve undergone ileocolonic resectioning, the ultimate question is where the “sweet spot” is for timing biologic therapy.

“In 2016, symptoms will still guide treatment,” said Dr. Miguel D. Regueiro, professor of medicine at the University of Pittsburgh and clinical medical director of the University’s IBD Center, during the clinical track of this year’s annual Advances in Inflammatory Bowel Diseases meeting, sponsored by the Crohn’s and Colitis Foundation of America. But when it comes to the exact timing of administering anti–tumor necrosis factor (TNF) agents, clinicians should look to risk factors for recurrence.

Whitney McKnight/Frontline Medical News

The notion that immediate treatment with a biologic after surgical resectioning is best is supported by phase III data from the international, multicenter PREVENT trial, for which Dr. Regueiro was principal investigator. It demonstrated that at week 79 and week 104, immediate treatment with the biologic infliximab 5 mg/kg every 8 weeks postsurgery in patients with high risk for recurrence (smokers, those with penetrating or fistulizing disease, or a history of resectioning) resulted in lower but not statistically significant rates of the composite endpoint of clinical recurrence and endoscopic scores greater than 2, when compared with placebo (P = .097 at 76 weeks and P = .098 at 104 weeks).

Dr. Regueiro noted in an interview that often, even though endoscopic recurrence scores might be high, following surgery, patients are in clinical remission and so do not report any symptoms. He noted that when only endoscopic outcomes prior to or at week 76 in the PREVENT trial were analyzed as the secondary endpoint, there was a statistically significant difference when compared with placebo: The 147 randomly assigned study arm participants had a recurrence rate of 22.4% vs. 51.3% in 150 controls (P less than .001). Further, Rutgeerts scores equal or greater than i-3 occurred in 83.1% of participants in the placebo group, compared with 28.4% in the infliximab group at week 76.

“The take-home message is that surgery induces a deep remission where patient’s ‘feel well’ and by using a clinical symptom score we do not detect recurrence, probably for years,” Dr. Regueiro said in the interview.

What about waiting to offer treatment?

Results from the POCER trial, also conducted internationally at a number of centers, support this approach.

In the trial, 174 postoperative patients at high risk for recurrence were randomly assigned in a 2:1 ratio to either standard care – colonoscopy at 18 months – or to receive a colonoscopy at 6 months, followed by medication if there was an endoscopic recurrence of i-2 or greater.

Both study arms were given metronidazole 400 mg twice a day for 3 months. If patients were intolerant, the dose was reduced to 200 mg twice daily or was stopped altogether. If they were high risk but medication naive, patients were given azathioprine 2 mg/kg or 6-mercaptopurine 1.5 mg/kg once daily, beginning within 1 month after surgery. Patients intolerant to this regime were administered adalimumab 160/80/40 mg accordingly, every other week.

At 18 months, those patients who’d been observed endoscopically at 6 months and given medication if necessary had a 49% rate of recurrence compared with 67% in the group given standard care, a statistically significant difference.

However, when Dr. Regueiro, who was not directly involved with the POCER trial, conducted an informal review of the data, he found that patients who’d been on thiopurines had an endoscopic recurrence rate at 6 months of 45% vs. the 21% rate in the adalimumab patients. “This means that waiting on anti-TNF and giving thiopurine meant nearly half the patients had recurrence in 6 months, compared with anti-TNF treated patients.”

So then, when should biologics enter the treatment picture?

Again, look to the risk profile, said Dr. Regueiro. Patients who are 30 years of age or younger, have ileocolonic disease, smoke, have penetrating disease, or have already had two or more surgeries or had a short duration between time of diagnosis and surgery are considered at high risk for return of the disease.

In his own practice, Dr. Regueiro said he puts all but the low-risk patients on some form of immediate postoperative medication. Patients at moderate risk, such as those who have had a resection within 10 years of diagnosis, receive 6-mercaptopurine or azathioprine plus metronidazole (if tolerated) and are given colonoscopy at 6-12 months postoperatively. If there is a recurrence at that point, then he will start the patient on an anti-TNF. If not, then he sees them again in 1-3 years for a colonoscopy. Dr. Regueiro treats patients at high risk for recurrence more frequently with combination therapies, immediately setting them on a regimen of anti-TNF plus immunosuppressive therapy followed by a 6-12 month postoperative colonoscopy after which he adjusts treatment if there is active disease, including increasing the dose of the biologic or switching to another one.

But just what length of time actually constitutes “immediately after surgery?” In the PREVENT trial, clinicians had up to 45 days to begin therapy, although Dr. Regueiro said he prefers to start between 2 and 4 weeks postsurgery, a number with which panel moderator Dr. David T. Rubin, codirector of the University of Chicago Digestive Diseases Center, agreed.

While these study results help pinpoint the range for when to use biologics, Dr. Regueiro said in the interview, “Future study is need to determine the ‘tipping point’ where postoperative Crohn’s disease recurrence results in significant bowel damage and renders medications ineffective. Finding the ‘biologic sweet spot’ of when to start aggressive therapy versus a ‘wait and watch’ approach remains the question.”

Dr. Regueiro disclosed he is a consultant for AbbVie, Janssen, UCB, Pfizer, and Takeda.

[email protected]

On Twitter @whitneymcknight

ORLANDO – To delay or prevent recurrence of Crohn’s disease in patients after they’ve undergone ileocolonic resectioning, the ultimate question is where the “sweet spot” is for timing biologic therapy.

“In 2016, symptoms will still guide treatment,” said Dr. Miguel D. Regueiro, professor of medicine at the University of Pittsburgh and clinical medical director of the University’s IBD Center, during the clinical track of this year’s annual Advances in Inflammatory Bowel Diseases meeting, sponsored by the Crohn’s and Colitis Foundation of America. But when it comes to the exact timing of administering anti–tumor necrosis factor (TNF) agents, clinicians should look to risk factors for recurrence.

Whitney McKnight/Frontline Medical News

The notion that immediate treatment with a biologic after surgical resectioning is best is supported by phase III data from the international, multicenter PREVENT trial, for which Dr. Regueiro was principal investigator. It demonstrated that at week 79 and week 104, immediate treatment with the biologic infliximab 5 mg/kg every 8 weeks postsurgery in patients with high risk for recurrence (smokers, those with penetrating or fistulizing disease, or a history of resectioning) resulted in lower but not statistically significant rates of the composite endpoint of clinical recurrence and endoscopic scores greater than 2, when compared with placebo (P = .097 at 76 weeks and P = .098 at 104 weeks).

Dr. Regueiro noted in an interview that often, even though endoscopic recurrence scores might be high, following surgery, patients are in clinical remission and so do not report any symptoms. He noted that when only endoscopic outcomes prior to or at week 76 in the PREVENT trial were analyzed as the secondary endpoint, there was a statistically significant difference when compared with placebo: The 147 randomly assigned study arm participants had a recurrence rate of 22.4% vs. 51.3% in 150 controls (P less than .001). Further, Rutgeerts scores equal or greater than i-3 occurred in 83.1% of participants in the placebo group, compared with 28.4% in the infliximab group at week 76.

“The take-home message is that surgery induces a deep remission where patient’s ‘feel well’ and by using a clinical symptom score we do not detect recurrence, probably for years,” Dr. Regueiro said in the interview.

What about waiting to offer treatment?

Results from the POCER trial, also conducted internationally at a number of centers, support this approach.

In the trial, 174 postoperative patients at high risk for recurrence were randomly assigned in a 2:1 ratio to either standard care – colonoscopy at 18 months – or to receive a colonoscopy at 6 months, followed by medication if there was an endoscopic recurrence of i-2 or greater.

Both study arms were given metronidazole 400 mg twice a day for 3 months. If patients were intolerant, the dose was reduced to 200 mg twice daily or was stopped altogether. If they were high risk but medication naive, patients were given azathioprine 2 mg/kg or 6-mercaptopurine 1.5 mg/kg once daily, beginning within 1 month after surgery. Patients intolerant to this regime were administered adalimumab 160/80/40 mg accordingly, every other week.

At 18 months, those patients who’d been observed endoscopically at 6 months and given medication if necessary had a 49% rate of recurrence compared with 67% in the group given standard care, a statistically significant difference.

However, when Dr. Regueiro, who was not directly involved with the POCER trial, conducted an informal review of the data, he found that patients who’d been on thiopurines had an endoscopic recurrence rate at 6 months of 45% vs. the 21% rate in the adalimumab patients. “This means that waiting on anti-TNF and giving thiopurine meant nearly half the patients had recurrence in 6 months, compared with anti-TNF treated patients.”

So then, when should biologics enter the treatment picture?

Again, look to the risk profile, said Dr. Regueiro. Patients who are 30 years of age or younger, have ileocolonic disease, smoke, have penetrating disease, or have already had two or more surgeries or had a short duration between time of diagnosis and surgery are considered at high risk for return of the disease.

In his own practice, Dr. Regueiro said he puts all but the low-risk patients on some form of immediate postoperative medication. Patients at moderate risk, such as those who have had a resection within 10 years of diagnosis, receive 6-mercaptopurine or azathioprine plus metronidazole (if tolerated) and are given colonoscopy at 6-12 months postoperatively. If there is a recurrence at that point, then he will start the patient on an anti-TNF. If not, then he sees them again in 1-3 years for a colonoscopy. Dr. Regueiro treats patients at high risk for recurrence more frequently with combination therapies, immediately setting them on a regimen of anti-TNF plus immunosuppressive therapy followed by a 6-12 month postoperative colonoscopy after which he adjusts treatment if there is active disease, including increasing the dose of the biologic or switching to another one.

But just what length of time actually constitutes “immediately after surgery?” In the PREVENT trial, clinicians had up to 45 days to begin therapy, although Dr. Regueiro said he prefers to start between 2 and 4 weeks postsurgery, a number with which panel moderator Dr. David T. Rubin, codirector of the University of Chicago Digestive Diseases Center, agreed.

While these study results help pinpoint the range for when to use biologics, Dr. Regueiro said in the interview, “Future study is need to determine the ‘tipping point’ where postoperative Crohn’s disease recurrence results in significant bowel damage and renders medications ineffective. Finding the ‘biologic sweet spot’ of when to start aggressive therapy versus a ‘wait and watch’ approach remains the question.”

Dr. Regueiro disclosed he is a consultant for AbbVie, Janssen, UCB, Pfizer, and Takeda.

[email protected]

On Twitter @whitneymcknight

ORLANDO – You can confidently treat mild to severe Clostridium difficile infection in persons with inflammatory bowel disease, without disrupting their immunosuppression or other treatments, according to an expert.

“If your patient with IBD needs a fecal transplant for C. diff., you should not be concerned about withholding it,” Dr. Alan C. Moss said during a basic science presentation at a conference on inflammatory bowel diseases (IBD), sponsored by the Crohn’s and Colitis Foundation of America. Dr. Moss is an associate professor of medicine and the director of translational research at Harvard Medical School, Boston.

The first step, after you’ve determined that your patient has a true C. diff. infection, as opposed to having only been colonized by the bacteria, is choosing the best antibiotic. “Unfortunately, almost all IBD patients are excluded from controlled trials of antibiotics in C. diff. infection, so all we really have to go on are retrospective cohort data,” said Dr. Moss.

One such study, uncontrolled for disease severity, showed that a third of 114 inpatients with IBD who had a co-occurring C. diff. infection had higher 30-day readmission rates when treated first with metronidazole, per current standards of care, compared with the remaining two-thirds of patients who were treated first with vancomycin. The metronidazole group also averaged double the length of stays of the vancomycin group (Antimicrob Agents Chemother. 2014 Sep;58:5054-9 [doi: 10.1128/AAC.02606-13]).

“This suggests that in IBD patients, especially for those who meet criteria for a severe C. diff. infection, vancomycin is the way to go,” Dr. Moss said, noting a trend of metronidazole for mild infections in this cohort having ever less efficacy.

Beyond mild infection, Dr. Moss said the first line of treatment should be vancomycin 125 mg four times daily, or 500 mg four times daily if it is complicated disease.

If your patient has recurrent C. diff. infection, Dr. Moss recommended a prolonged taper of vancomycin, but to be vigilant about it being truly an infection and not a flare-up of colonized bacteria.

“My bar for doing fecal transplant in these patients has dropped considerably in the last few years, because if you really want to squeeze out the niche that C. diff. occupies in the microbiome, fecal transplant is really the most effective way we have of doing that,” Dr. Moss said.

While there is a division in the field over whether to continue immunosuppression during antibiotic treatment, Dr. Moss cited a small study indicating that if a patient were on two or more immunosuppressants, they had a higher risk of death, megacolon, or shock during C. diff. treatment. “I think it’s hard to draw many conclusions from that,” Dr. Moss said. “It may just be a surrogate marker of severity of disease rather than infection, per se.”

The standard of care for recurrent and refractory C. diff. infection is now fecal transplant, according to Dr. Moss. A recent study of fecal transplantation showed an 89% cure rate of C. diff. infection after a single fecal transplant in IBD patients. Of the 36 IBD patients in the study, half of whom were on biologic and immunosuppressive therapies, four experienced disease flare-ups (Am J Gastroenterol. 2014 Jul;109:1065-71 [doi: 10.1038/ajg.2014.133]. N Engl J Med. 2013 Jan 31;368:474-5 [doi: 10.1056/NEJMe1214816]).

As for determining if there is an actual infection rather than colonization of C. diff., Dr. Moss said switching from using ELISA (enzyme-linked immunoassay) testing to PCR (polymerase chain reaction) testing instead was helpful in first-time infections because the latter is more sensitive for determining actual infection; however, if a patient has recurrent infection, the higher clinical specificity of PCR makes it harder to tell if a positive result is infection or simply colonization.

Some institutions have dropped ELISA testing altogether, Dr. Moss said, although he thinks the use of single molecule array testing is, with its exponential sensitivity, a “good half-way step” between ELISA and PCR, and is useful for determining who is colonized vs. who is actually producing the toxin, even at a very low level.

Dr. Moss disclosed he has consulted for Janssen, Theravance, and Seres, and has received research support from the National Institute for Diabetes, Digestive, and Kidney Disease, and Helmsley.

[email protected]

On Twitter @whitneymcknight

ORLANDO – You can confidently treat mild to severe Clostridium difficile infection in persons with inflammatory bowel disease, without disrupting their immunosuppression or other treatments, according to an expert.

“If your patient with IBD needs a fecal transplant for C. diff., you should not be concerned about withholding it,” Dr. Alan C. Moss said during a basic science presentation at a conference on inflammatory bowel diseases (IBD), sponsored by the Crohn’s and Colitis Foundation of America. Dr. Moss is an associate professor of medicine and the director of translational research at Harvard Medical School, Boston.

The first step, after you’ve determined that your patient has a true C. diff. infection, as opposed to having only been colonized by the bacteria, is choosing the best antibiotic. “Unfortunately, almost all IBD patients are excluded from controlled trials of antibiotics in C. diff. infection, so all we really have to go on are retrospective cohort data,” said Dr. Moss.

One such study, uncontrolled for disease severity, showed that a third of 114 inpatients with IBD who had a co-occurring C. diff. infection had higher 30-day readmission rates when treated first with metronidazole, per current standards of care, compared with the remaining two-thirds of patients who were treated first with vancomycin. The metronidazole group also averaged double the length of stays of the vancomycin group (Antimicrob Agents Chemother. 2014 Sep;58:5054-9 [doi: 10.1128/AAC.02606-13]).

“This suggests that in IBD patients, especially for those who meet criteria for a severe C. diff. infection, vancomycin is the way to go,” Dr. Moss said, noting a trend of metronidazole for mild infections in this cohort having ever less efficacy.

Beyond mild infection, Dr. Moss said the first line of treatment should be vancomycin 125 mg four times daily, or 500 mg four times daily if it is complicated disease.

If your patient has recurrent C. diff. infection, Dr. Moss recommended a prolonged taper of vancomycin, but to be vigilant about it being truly an infection and not a flare-up of colonized bacteria.

“My bar for doing fecal transplant in these patients has dropped considerably in the last few years, because if you really want to squeeze out the niche that C. diff. occupies in the microbiome, fecal transplant is really the most effective way we have of doing that,” Dr. Moss said.

While there is a division in the field over whether to continue immunosuppression during antibiotic treatment, Dr. Moss cited a small study indicating that if a patient were on two or more immunosuppressants, they had a higher risk of death, megacolon, or shock during C. diff. treatment. “I think it’s hard to draw many conclusions from that,” Dr. Moss said. “It may just be a surrogate marker of severity of disease rather than infection, per se.”

The standard of care for recurrent and refractory C. diff. infection is now fecal transplant, according to Dr. Moss. A recent study of fecal transplantation showed an 89% cure rate of C. diff. infection after a single fecal transplant in IBD patients. Of the 36 IBD patients in the study, half of whom were on biologic and immunosuppressive therapies, four experienced disease flare-ups (Am J Gastroenterol. 2014 Jul;109:1065-71 [doi: 10.1038/ajg.2014.133]. N Engl J Med. 2013 Jan 31;368:474-5 [doi: 10.1056/NEJMe1214816]).

As for determining if there is an actual infection rather than colonization of C. diff., Dr. Moss said switching from using ELISA (enzyme-linked immunoassay) testing to PCR (polymerase chain reaction) testing instead was helpful in first-time infections because the latter is more sensitive for determining actual infection; however, if a patient has recurrent infection, the higher clinical specificity of PCR makes it harder to tell if a positive result is infection or simply colonization.

Some institutions have dropped ELISA testing altogether, Dr. Moss said, although he thinks the use of single molecule array testing is, with its exponential sensitivity, a “good half-way step” between ELISA and PCR, and is useful for determining who is colonized vs. who is actually producing the toxin, even at a very low level.

Dr. Moss disclosed he has consulted for Janssen, Theravance, and Seres, and has received research support from the National Institute for Diabetes, Digestive, and Kidney Disease, and Helmsley.

[email protected]

On Twitter @whitneymcknight

ORLANDO – You can confidently treat mild to severe Clostridium difficile infection in persons with inflammatory bowel disease, without disrupting their immunosuppression or other treatments, according to an expert.

“If your patient with IBD needs a fecal transplant for C. diff., you should not be concerned about withholding it,” Dr. Alan C. Moss said during a basic science presentation at a conference on inflammatory bowel diseases (IBD), sponsored by the Crohn’s and Colitis Foundation of America. Dr. Moss is an associate professor of medicine and the director of translational research at Harvard Medical School, Boston.

The first step, after you’ve determined that your patient has a true C. diff. infection, as opposed to having only been colonized by the bacteria, is choosing the best antibiotic. “Unfortunately, almost all IBD patients are excluded from controlled trials of antibiotics in C. diff. infection, so all we really have to go on are retrospective cohort data,” said Dr. Moss.

One such study, uncontrolled for disease severity, showed that a third of 114 inpatients with IBD who had a co-occurring C. diff. infection had higher 30-day readmission rates when treated first with metronidazole, per current standards of care, compared with the remaining two-thirds of patients who were treated first with vancomycin. The metronidazole group also averaged double the length of stays of the vancomycin group (Antimicrob Agents Chemother. 2014 Sep;58:5054-9 [doi: 10.1128/AAC.02606-13]).

“This suggests that in IBD patients, especially for those who meet criteria for a severe C. diff. infection, vancomycin is the way to go,” Dr. Moss said, noting a trend of metronidazole for mild infections in this cohort having ever less efficacy.

Beyond mild infection, Dr. Moss said the first line of treatment should be vancomycin 125 mg four times daily, or 500 mg four times daily if it is complicated disease.

If your patient has recurrent C. diff. infection, Dr. Moss recommended a prolonged taper of vancomycin, but to be vigilant about it being truly an infection and not a flare-up of colonized bacteria.

“My bar for doing fecal transplant in these patients has dropped considerably in the last few years, because if you really want to squeeze out the niche that C. diff. occupies in the microbiome, fecal transplant is really the most effective way we have of doing that,” Dr. Moss said.

While there is a division in the field over whether to continue immunosuppression during antibiotic treatment, Dr. Moss cited a small study indicating that if a patient were on two or more immunosuppressants, they had a higher risk of death, megacolon, or shock during C. diff. treatment. “I think it’s hard to draw many conclusions from that,” Dr. Moss said. “It may just be a surrogate marker of severity of disease rather than infection, per se.”

The standard of care for recurrent and refractory C. diff. infection is now fecal transplant, according to Dr. Moss. A recent study of fecal transplantation showed an 89% cure rate of C. diff. infection after a single fecal transplant in IBD patients. Of the 36 IBD patients in the study, half of whom were on biologic and immunosuppressive therapies, four experienced disease flare-ups (Am J Gastroenterol. 2014 Jul;109:1065-71 [doi: 10.1038/ajg.2014.133]. N Engl J Med. 2013 Jan 31;368:474-5 [doi: 10.1056/NEJMe1214816]).

As for determining if there is an actual infection rather than colonization of C. diff., Dr. Moss said switching from using ELISA (enzyme-linked immunoassay) testing to PCR (polymerase chain reaction) testing instead was helpful in first-time infections because the latter is more sensitive for determining actual infection; however, if a patient has recurrent infection, the higher clinical specificity of PCR makes it harder to tell if a positive result is infection or simply colonization.

Some institutions have dropped ELISA testing altogether, Dr. Moss said, although he thinks the use of single molecule array testing is, with its exponential sensitivity, a “good half-way step” between ELISA and PCR, and is useful for determining who is colonized vs. who is actually producing the toxin, even at a very low level.

Dr. Moss disclosed he has consulted for Janssen, Theravance, and Seres, and has received research support from the National Institute for Diabetes, Digestive, and Kidney Disease, and Helmsley.

[email protected]

On Twitter @whitneymcknight

ORLANDO – Regardless of what you think about using biosimilars, chances are you won’t be able to avoid using them if you already use biologics.

That’s according to Dr. David T. Rubin, codirector of the Digestive Diseases Center at the University of Chicago. “They’re coming and they will influence our practice, ” he told a clinical track audience at a conference on inflammatory bowel disease.

Before exploring how these medications may change how you treat patients, here’s a look at what they are and how they’re brought to market.

First, a little basic science review of small-molecule medications vs. biologic ones. Small-molecule agents are simple structures, which are stable enough to be replicated, do not tend to cause immunogenicity, and require very little in the way of testing for quality assurance.

By contrast, biologic medicines, including monoclonal antibodies, are complex structures – in some cases, highly complex – that are replicable, but often with a high degree of difficulty. Unlike small-molecule medicines, biologic drugs cannot be mass produced and require almost 250 sophisticated tests to ensure quality. They are less stable and can trigger an immunogenic response. The manufacturing process for biologics is so precise that the slightest disturbance in development can affect whether the medication is functional.

As a result, the typical development timeline for these medications is between 7 and 8 years, with costs running as high as $250 million each. Currently, there are more than 650 recombinant therapeutics in development worldwide, more than half of which are in the preclinical stage. The top original products being copied are adalimumab at 13, and infliximab with 9. Meanwhile, at least five as-of-yet unpublished studies are looking at how these potential adalimumab and infliximab biosimilars perform in inflammatory bowel disease (IBD), Dr. Rubin said. Biosimilars are used worldwide, primarily in Europe and Asia.

But when these biosimilars reach our shores, don’t call them generics. “I encourage you to not use that term, even when discussing them with patients,” Dr. Rubin said. Still, because the Food and Drug Administration says that a biosimilar should have no greater risk for adverse events or diminished efficacy compared with the original biologic just as with generics, pharmacists are within their rights to substitute biosimilars for original biologics without prescriber intervention.

That’s why, “There must be pharmacovigilance with biosimilars, just like with generics, after the drug is brought to market,” Dr. Rubin said.

Biosimilars are also not “biobetters,” medications that have modifications added to the original biologic product in order to improve their clinical performance. While biobetters can be patented, they do not have legal or regulatory status, however, because they are considered new drugs.

The FDA defines biosimilars as a biological product that is highly similar to the reference product, with no clinically meaningful safety, purity, or potency differences from the reference product.

Early in 2015, the biosimilar filgrastim-sndz (Zarxio TM, Sandoz-Novartis), which has been available in Europe since 2009, entered the U.S. market. With its biosimilarity to Filgrastim (Sandoz-Novartis), the medication’s primary indications are for various cancers and chronic neutropenia.

To help expedite bringing the medications to market, FDA guidance data requirements for biosimilars is abbreviated when compared with that for biologics. Rather than ask developers to conduct clinical trials, developers must provide at least one comparative study between the biosimilar and its original, according to the original drug’s indication. There also is what Dr. Rubin called a “weighted reliance” on analytical similarity to the original. In addition, no phase II dose-ranging studies are required. Indication extrapolation is also possible, meaning that safety and efficacy data leading to a biosimilar being approved for say, rheumatoid arthritis, could also be applied to Crohn’s disease.

So, what does all this mean for your patients? It depends upon in which state you practice: Even when a recombinant product meets the FDA criteria, whether or not a patient can be placed on a biosimilar comes down to state regulation. At present, 19 states have passed laws as to how and when biosimilars can be swapped out, most of them stipulating that a patient be notified when it occurs. Physicians maintain their rights to ask pharmacists to “dispense as written,” but since biosimilars are cheaper than their originals, you won’t necessarily get around mounting pressure from third-party payers to contain costs.

Dr. Rubin said this potential friction between insurers and physicians could result in delays with adverse effect on the patient. “If the insurance company says they prefer another agent over the one a patient is receiving, we all know about the unexpected delays that can occur when switching.”

Dr. Rubin predicted that the logistics of prescribing will be complicated by pharmaceutical marketing efforts. He noted the similar names of Remsima (Hospira) vs. Remicade (Janssen), Inflectra (Hospira) vs. infliximab generic. “It could be confusing for all of us.”

The question of how the drug will fare once inside the patient is still a matter of debate.

“The major issue is immunogenicity ... it’s impossible to predict in vitro,” said Dr. Brian Feagan, a copanelist with Dr. Rubin, and a professor of medicine at the University of Western Ontario in London, Canada. “Immunogenicity is determined by product-related factors, and a lot of clinical ones such as immunosuppression, coadministration, route of administration, disease-specific factors.”

The only way to truly determine the impact on immunogenicity of interchangeability, whether because of third-party payer stipulations or physician’s choice, is to do multiple switching trials, said Dr. Feagan.

But Dr. Stephen B. Hanauer, the Clifford Joseph Barborka Professor of Medicine in Gastroenterology and Hepatology at Northwestern University (Chicago), said that’s not likely to happen. “There’s no time for that as the FDA regulatory evaluation proceeds,” he said in an interview.

“The trial would take 2 years to accomplish, would need large numbers of patients in order to identify potential small differences, and would be too expensive.” All of which would defeat the purpose of the expedited approval process, Dr. Hanauer said, because the decision by Congress to give biosimilars the green light was to reduce cost.

On the other hand, said Dr. Feagan, the experiment on switching probably has already been done. That’s because despite what he referred to as efforts by pharmaceutical manufacturers to reassure physicians there is no drift from the original product, heterogeneity is inevitable.

These iterative qualities, according to Dr. Hanauer, essentially make the original products into biosimilars of themselves. Add to that, he said that depending upon the company used to perform the assays to determine immunogenicity, the range of results can vary widely, and you end up having to learn to live with a certain amount of uncertainty. “I’m not afraid of biosimilars,” Dr. Hanauer said while discussing biosimilars during an audience question time at the meeting.

“We are a little bit timid about biosimilars, but my sense is we will find our comfort level in the next few years, and we will start using them frequently,” Dr. Miguel Regueiro, medical director of the IBD Center at the University of Pittsburgh, said in an interview. “I think immunogenicity to biosimilars will be the same immunogenicity to the innovative biologics, but I don’t think we’re going to be comfortable with interchanging a biosimilar with a[n] original biologic because of the potential immunogenicity that can occur by switching between agents.”

Whitney McKnight/Frontline Medical News

Whether biosimilars can be used in place of their originals, said both Dr. Feagan and Dr. Hanauer, will come down to how extrapolated data is interpreted.

“I think the biggest debate the FDA is going to have [when indicating biosimilars for IBD] is overextrapolation,” Dr. Hanauer said in the interview. Since the FDA does not require clinical trials for biosimilars, but relies upon analytics instead, and because there are far less clinical data for biologics in IBD than there are for diseases such as rheumatoid or psoriatic arthritis, manufacturers will turn to those studies to demonstrate efficacy between originals and recombinants. “If 99.9% of the analytic assays and the clinical data in rheumatoid arthritis are virtually the same, I would assume that the data in inflammatory bowel disease is going to be virtually the same.”

However, at least in Canada, that was not the opinion of regulators who decided against approving the extrapolation of infliximab clinical data for indicating its biosimilar in IBD, but did allow extrapolation of the data for rheumatoid arthritis. “Health Canada decided that the antibody-dependent, cell-mediated cytotoxicity was different for IBD,” said Dr. Feagan.

Predicting the primacy of cost over keeping patients in remission, but at least for now, Dr. Rubin said the question of cost is “huge. Based on the European and Asian experience, the day one of these new products becomes available, the price of the existing therapies drops anywhere from 15% to 30%.”

Recent data places the cost of remission in the United States using infliximab at about $15,000.

Dr. Regueiro said these market forces are a good thing. “I don’t look at biosimilars in a negative context whatsoever. I think they are a necessary part of health care reform. Cost is definitely a driver, and that’s not bad.”

The meeting was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Rubin has financial and consulting relationships with AbbVie, Janssen, Takeda, and numerous other pharmaceutical companies. Dr. Feagan has numerous relationships with pharmaceutical companies, including Abbott, Janssen, Teva, and others. Dr. Hanauer has served on the board of AbbVie and has financial relationships with numerous other pharmaceutical manufacturers. Dr. Regueiro did not have any disclosures relevant to this story.

[email protected]

On Twitter @whitneymcknight

This article was updated 1/6/16.

ORLANDO – Regardless of what you think about using biosimilars, chances are you won’t be able to avoid using them if you already use biologics.

That’s according to Dr. David T. Rubin, codirector of the Digestive Diseases Center at the University of Chicago. “They’re coming and they will influence our practice, ” he told a clinical track audience at a conference on inflammatory bowel disease.

Before exploring how these medications may change how you treat patients, here’s a look at what they are and how they’re brought to market.

First, a little basic science review of small-molecule medications vs. biologic ones. Small-molecule agents are simple structures, which are stable enough to be replicated, do not tend to cause immunogenicity, and require very little in the way of testing for quality assurance.

By contrast, biologic medicines, including monoclonal antibodies, are complex structures – in some cases, highly complex – that are replicable, but often with a high degree of difficulty. Unlike small-molecule medicines, biologic drugs cannot be mass produced and require almost 250 sophisticated tests to ensure quality. They are less stable and can trigger an immunogenic response. The manufacturing process for biologics is so precise that the slightest disturbance in development can affect whether the medication is functional.

As a result, the typical development timeline for these medications is between 7 and 8 years, with costs running as high as $250 million each. Currently, there are more than 650 recombinant therapeutics in development worldwide, more than half of which are in the preclinical stage. The top original products being copied are adalimumab at 13, and infliximab with 9. Meanwhile, at least five as-of-yet unpublished studies are looking at how these potential adalimumab and infliximab biosimilars perform in inflammatory bowel disease (IBD), Dr. Rubin said. Biosimilars are used worldwide, primarily in Europe and Asia.

But when these biosimilars reach our shores, don’t call them generics. “I encourage you to not use that term, even when discussing them with patients,” Dr. Rubin said. Still, because the Food and Drug Administration says that a biosimilar should have no greater risk for adverse events or diminished efficacy compared with the original biologic just as with generics, pharmacists are within their rights to substitute biosimilars for original biologics without prescriber intervention.

That’s why, “There must be pharmacovigilance with biosimilars, just like with generics, after the drug is brought to market,” Dr. Rubin said.

Biosimilars are also not “biobetters,” medications that have modifications added to the original biologic product in order to improve their clinical performance. While biobetters can be patented, they do not have legal or regulatory status, however, because they are considered new drugs.

The FDA defines biosimilars as a biological product that is highly similar to the reference product, with no clinically meaningful safety, purity, or potency differences from the reference product.

Early in 2015, the biosimilar filgrastim-sndz (Zarxio TM, Sandoz-Novartis), which has been available in Europe since 2009, entered the U.S. market. With its biosimilarity to Filgrastim (Sandoz-Novartis), the medication’s primary indications are for various cancers and chronic neutropenia.

To help expedite bringing the medications to market, FDA guidance data requirements for biosimilars is abbreviated when compared with that for biologics. Rather than ask developers to conduct clinical trials, developers must provide at least one comparative study between the biosimilar and its original, according to the original drug’s indication. There also is what Dr. Rubin called a “weighted reliance” on analytical similarity to the original. In addition, no phase II dose-ranging studies are required. Indication extrapolation is also possible, meaning that safety and efficacy data leading to a biosimilar being approved for say, rheumatoid arthritis, could also be applied to Crohn’s disease.

So, what does all this mean for your patients? It depends upon in which state you practice: Even when a recombinant product meets the FDA criteria, whether or not a patient can be placed on a biosimilar comes down to state regulation. At present, 19 states have passed laws as to how and when biosimilars can be swapped out, most of them stipulating that a patient be notified when it occurs. Physicians maintain their rights to ask pharmacists to “dispense as written,” but since biosimilars are cheaper than their originals, you won’t necessarily get around mounting pressure from third-party payers to contain costs.

Dr. Rubin said this potential friction between insurers and physicians could result in delays with adverse effect on the patient. “If the insurance company says they prefer another agent over the one a patient is receiving, we all know about the unexpected delays that can occur when switching.”

Dr. Rubin predicted that the logistics of prescribing will be complicated by pharmaceutical marketing efforts. He noted the similar names of Remsima (Hospira) vs. Remicade (Janssen), Inflectra (Hospira) vs. infliximab generic. “It could be confusing for all of us.”

The question of how the drug will fare once inside the patient is still a matter of debate.

“The major issue is immunogenicity ... it’s impossible to predict in vitro,” said Dr. Brian Feagan, a copanelist with Dr. Rubin, and a professor of medicine at the University of Western Ontario in London, Canada. “Immunogenicity is determined by product-related factors, and a lot of clinical ones such as immunosuppression, coadministration, route of administration, disease-specific factors.”

The only way to truly determine the impact on immunogenicity of interchangeability, whether because of third-party payer stipulations or physician’s choice, is to do multiple switching trials, said Dr. Feagan.

But Dr. Stephen B. Hanauer, the Clifford Joseph Barborka Professor of Medicine in Gastroenterology and Hepatology at Northwestern University (Chicago), said that’s not likely to happen. “There’s no time for that as the FDA regulatory evaluation proceeds,” he said in an interview.

“The trial would take 2 years to accomplish, would need large numbers of patients in order to identify potential small differences, and would be too expensive.” All of which would defeat the purpose of the expedited approval process, Dr. Hanauer said, because the decision by Congress to give biosimilars the green light was to reduce cost.

On the other hand, said Dr. Feagan, the experiment on switching probably has already been done. That’s because despite what he referred to as efforts by pharmaceutical manufacturers to reassure physicians there is no drift from the original product, heterogeneity is inevitable.

These iterative qualities, according to Dr. Hanauer, essentially make the original products into biosimilars of themselves. Add to that, he said that depending upon the company used to perform the assays to determine immunogenicity, the range of results can vary widely, and you end up having to learn to live with a certain amount of uncertainty. “I’m not afraid of biosimilars,” Dr. Hanauer said while discussing biosimilars during an audience question time at the meeting.

“We are a little bit timid about biosimilars, but my sense is we will find our comfort level in the next few years, and we will start using them frequently,” Dr. Miguel Regueiro, medical director of the IBD Center at the University of Pittsburgh, said in an interview. “I think immunogenicity to biosimilars will be the same immunogenicity to the innovative biologics, but I don’t think we’re going to be comfortable with interchanging a biosimilar with a[n] original biologic because of the potential immunogenicity that can occur by switching between agents.”

Whitney McKnight/Frontline Medical News

Whether biosimilars can be used in place of their originals, said both Dr. Feagan and Dr. Hanauer, will come down to how extrapolated data is interpreted.

“I think the biggest debate the FDA is going to have [when indicating biosimilars for IBD] is overextrapolation,” Dr. Hanauer said in the interview. Since the FDA does not require clinical trials for biosimilars, but relies upon analytics instead, and because there are far less clinical data for biologics in IBD than there are for diseases such as rheumatoid or psoriatic arthritis, manufacturers will turn to those studies to demonstrate efficacy between originals and recombinants. “If 99.9% of the analytic assays and the clinical data in rheumatoid arthritis are virtually the same, I would assume that the data in inflammatory bowel disease is going to be virtually the same.”

However, at least in Canada, that was not the opinion of regulators who decided against approving the extrapolation of infliximab clinical data for indicating its biosimilar in IBD, but did allow extrapolation of the data for rheumatoid arthritis. “Health Canada decided that the antibody-dependent, cell-mediated cytotoxicity was different for IBD,” said Dr. Feagan.

Predicting the primacy of cost over keeping patients in remission, but at least for now, Dr. Rubin said the question of cost is “huge. Based on the European and Asian experience, the day one of these new products becomes available, the price of the existing therapies drops anywhere from 15% to 30%.”

Recent data places the cost of remission in the United States using infliximab at about $15,000.

Dr. Regueiro said these market forces are a good thing. “I don’t look at biosimilars in a negative context whatsoever. I think they are a necessary part of health care reform. Cost is definitely a driver, and that’s not bad.”

The meeting was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Rubin has financial and consulting relationships with AbbVie, Janssen, Takeda, and numerous other pharmaceutical companies. Dr. Feagan has numerous relationships with pharmaceutical companies, including Abbott, Janssen, Teva, and others. Dr. Hanauer has served on the board of AbbVie and has financial relationships with numerous other pharmaceutical manufacturers. Dr. Regueiro did not have any disclosures relevant to this story.

[email protected]

On Twitter @whitneymcknight

This article was updated 1/6/16.

ORLANDO – Regardless of what you think about using biosimilars, chances are you won’t be able to avoid using them if you already use biologics.

That’s according to Dr. David T. Rubin, codirector of the Digestive Diseases Center at the University of Chicago. “They’re coming and they will influence our practice, ” he told a clinical track audience at a conference on inflammatory bowel disease.

Before exploring how these medications may change how you treat patients, here’s a look at what they are and how they’re brought to market.

First, a little basic science review of small-molecule medications vs. biologic ones. Small-molecule agents are simple structures, which are stable enough to be replicated, do not tend to cause immunogenicity, and require very little in the way of testing for quality assurance.

By contrast, biologic medicines, including monoclonal antibodies, are complex structures – in some cases, highly complex – that are replicable, but often with a high degree of difficulty. Unlike small-molecule medicines, biologic drugs cannot be mass produced and require almost 250 sophisticated tests to ensure quality. They are less stable and can trigger an immunogenic response. The manufacturing process for biologics is so precise that the slightest disturbance in development can affect whether the medication is functional.

As a result, the typical development timeline for these medications is between 7 and 8 years, with costs running as high as $250 million each. Currently, there are more than 650 recombinant therapeutics in development worldwide, more than half of which are in the preclinical stage. The top original products being copied are adalimumab at 13, and infliximab with 9. Meanwhile, at least five as-of-yet unpublished studies are looking at how these potential adalimumab and infliximab biosimilars perform in inflammatory bowel disease (IBD), Dr. Rubin said. Biosimilars are used worldwide, primarily in Europe and Asia.

But when these biosimilars reach our shores, don’t call them generics. “I encourage you to not use that term, even when discussing them with patients,” Dr. Rubin said. Still, because the Food and Drug Administration says that a biosimilar should have no greater risk for adverse events or diminished efficacy compared with the original biologic just as with generics, pharmacists are within their rights to substitute biosimilars for original biologics without prescriber intervention.

That’s why, “There must be pharmacovigilance with biosimilars, just like with generics, after the drug is brought to market,” Dr. Rubin said.

Biosimilars are also not “biobetters,” medications that have modifications added to the original biologic product in order to improve their clinical performance. While biobetters can be patented, they do not have legal or regulatory status, however, because they are considered new drugs.

The FDA defines biosimilars as a biological product that is highly similar to the reference product, with no clinically meaningful safety, purity, or potency differences from the reference product.

Early in 2015, the biosimilar filgrastim-sndz (Zarxio TM, Sandoz-Novartis), which has been available in Europe since 2009, entered the U.S. market. With its biosimilarity to Filgrastim (Sandoz-Novartis), the medication’s primary indications are for various cancers and chronic neutropenia.

To help expedite bringing the medications to market, FDA guidance data requirements for biosimilars is abbreviated when compared with that for biologics. Rather than ask developers to conduct clinical trials, developers must provide at least one comparative study between the biosimilar and its original, according to the original drug’s indication. There also is what Dr. Rubin called a “weighted reliance” on analytical similarity to the original. In addition, no phase II dose-ranging studies are required. Indication extrapolation is also possible, meaning that safety and efficacy data leading to a biosimilar being approved for say, rheumatoid arthritis, could also be applied to Crohn’s disease.

So, what does all this mean for your patients? It depends upon in which state you practice: Even when a recombinant product meets the FDA criteria, whether or not a patient can be placed on a biosimilar comes down to state regulation. At present, 19 states have passed laws as to how and when biosimilars can be swapped out, most of them stipulating that a patient be notified when it occurs. Physicians maintain their rights to ask pharmacists to “dispense as written,” but since biosimilars are cheaper than their originals, you won’t necessarily get around mounting pressure from third-party payers to contain costs.

Dr. Rubin said this potential friction between insurers and physicians could result in delays with adverse effect on the patient. “If the insurance company says they prefer another agent over the one a patient is receiving, we all know about the unexpected delays that can occur when switching.”

Dr. Rubin predicted that the logistics of prescribing will be complicated by pharmaceutical marketing efforts. He noted the similar names of Remsima (Hospira) vs. Remicade (Janssen), Inflectra (Hospira) vs. infliximab generic. “It could be confusing for all of us.”

The question of how the drug will fare once inside the patient is still a matter of debate.

“The major issue is immunogenicity ... it’s impossible to predict in vitro,” said Dr. Brian Feagan, a copanelist with Dr. Rubin, and a professor of medicine at the University of Western Ontario in London, Canada. “Immunogenicity is determined by product-related factors, and a lot of clinical ones such as immunosuppression, coadministration, route of administration, disease-specific factors.”

The only way to truly determine the impact on immunogenicity of interchangeability, whether because of third-party payer stipulations or physician’s choice, is to do multiple switching trials, said Dr. Feagan.

But Dr. Stephen B. Hanauer, the Clifford Joseph Barborka Professor of Medicine in Gastroenterology and Hepatology at Northwestern University (Chicago), said that’s not likely to happen. “There’s no time for that as the FDA regulatory evaluation proceeds,” he said in an interview.

“The trial would take 2 years to accomplish, would need large numbers of patients in order to identify potential small differences, and would be too expensive.” All of which would defeat the purpose of the expedited approval process, Dr. Hanauer said, because the decision by Congress to give biosimilars the green light was to reduce cost.

On the other hand, said Dr. Feagan, the experiment on switching probably has already been done. That’s because despite what he referred to as efforts by pharmaceutical manufacturers to reassure physicians there is no drift from the original product, heterogeneity is inevitable.

These iterative qualities, according to Dr. Hanauer, essentially make the original products into biosimilars of themselves. Add to that, he said that depending upon the company used to perform the assays to determine immunogenicity, the range of results can vary widely, and you end up having to learn to live with a certain amount of uncertainty. “I’m not afraid of biosimilars,” Dr. Hanauer said while discussing biosimilars during an audience question time at the meeting.

“We are a little bit timid about biosimilars, but my sense is we will find our comfort level in the next few years, and we will start using them frequently,” Dr. Miguel Regueiro, medical director of the IBD Center at the University of Pittsburgh, said in an interview. “I think immunogenicity to biosimilars will be the same immunogenicity to the innovative biologics, but I don’t think we’re going to be comfortable with interchanging a biosimilar with a[n] original biologic because of the potential immunogenicity that can occur by switching between agents.”

Whitney McKnight/Frontline Medical News

Whether biosimilars can be used in place of their originals, said both Dr. Feagan and Dr. Hanauer, will come down to how extrapolated data is interpreted.

“I think the biggest debate the FDA is going to have [when indicating biosimilars for IBD] is overextrapolation,” Dr. Hanauer said in the interview. Since the FDA does not require clinical trials for biosimilars, but relies upon analytics instead, and because there are far less clinical data for biologics in IBD than there are for diseases such as rheumatoid or psoriatic arthritis, manufacturers will turn to those studies to demonstrate efficacy between originals and recombinants. “If 99.9% of the analytic assays and the clinical data in rheumatoid arthritis are virtually the same, I would assume that the data in inflammatory bowel disease is going to be virtually the same.”

However, at least in Canada, that was not the opinion of regulators who decided against approving the extrapolation of infliximab clinical data for indicating its biosimilar in IBD, but did allow extrapolation of the data for rheumatoid arthritis. “Health Canada decided that the antibody-dependent, cell-mediated cytotoxicity was different for IBD,” said Dr. Feagan.

Predicting the primacy of cost over keeping patients in remission, but at least for now, Dr. Rubin said the question of cost is “huge. Based on the European and Asian experience, the day one of these new products becomes available, the price of the existing therapies drops anywhere from 15% to 30%.”

Recent data places the cost of remission in the United States using infliximab at about $15,000.

Dr. Regueiro said these market forces are a good thing. “I don’t look at biosimilars in a negative context whatsoever. I think they are a necessary part of health care reform. Cost is definitely a driver, and that’s not bad.”

The meeting was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Rubin has financial and consulting relationships with AbbVie, Janssen, Takeda, and numerous other pharmaceutical companies. Dr. Feagan has numerous relationships with pharmaceutical companies, including Abbott, Janssen, Teva, and others. Dr. Hanauer has served on the board of AbbVie and has financial relationships with numerous other pharmaceutical manufacturers. Dr. Regueiro did not have any disclosures relevant to this story.

[email protected]

On Twitter @whitneymcknight

This article was updated 1/6/16.