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Biosimilars Have Driven Down Cost of Infliximab
LAS VEGAS — , according to two new retrospective analyses that separately looked at private insurance and Medicare patients.
“It is interesting to see that biosimilar use is increasing in patients with Medicare insurance in the U.S. since introduction into the market. This shows that clinicians are getting more comfortable with their use in clinical practice,” said Sara Horst, MD, associate professor of gastroenterology, hepatology, and nutrition at Vanderbilt University Medical Center in Nashville, Tennessee. That “is a continued important question in use, especially in the older population,” Dr. Horst said at the poster session where the two studies were presented, at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
One study examined Medicare part D participants. The researchers included infliximab prescriptions between 2013 and 2021, with a break in 2017 when biosimilars were first introduced. Between 2013 and 2017, there was a 93.7% annual increase in infliximab cost, and a 29.0% increase in annual claims. Between 2017 and 2021, those numbers declined to 23.9% and 12.1%, respectively. The researchers also examined trends by individual states and found a wide range of results. “Nationwide, it seems to be doing exactly what you’d expect, and I’d say it’s encouraging. This is exactly what you want with the introduction of biosimilars, and this is what you want for the patient population. But there are some states that have not really kept up with the rest of the country, and may need to look further into what types of trends are there,” said Modan Goldman, who presented the study. He is a medical student at Carle Illinois College of Medicine in Urbana, Illinois.
The other study looked at use of infliximab versus a biosimilar between 2015 and 2021 in 42,009 patients 64 or younger, drawing data from Merative Marketscan Commercial Claims and Encounters Database. They excluded government-funded insurance. Between January 2015 and December 2017, the cost of a vial of infliximab increased by $6.31 per month, reaching a maxim cost of $1,491 per vial. In January 2018, the cost decreased by $62 per vial, with a downward trend after that of $12.93 per vial per month.
“[Getting] access to these drugs, especially for pediatric IBD, has been an uphill battle with insurance companies and getting the medication and the doses we want,” said Samantha Paglinco, DO, who presented the Marketscan study.
The findings demonstrated clear cost reductions. “At the beginning of our period, infliximab originator Remicade was a little over $1,200 per vial, and at the end of our period of 2021, we expected it to be around $1,800 per vial. However, with the introduction of multiple infliximab biosimilars, we did see it come down to $800 per vial, which generated a savings of $1,000, which is pretty significant. We’re hoping that by generating overall cost savings to insurance companies, this will allow for greater access, because we know infliximab is such a good medication for pediatric IBD and for many other autoimmune conditions,” said Dr. Paglinco, a pediatric GI fellow at Nationwide Children’s Hospital in Columbus, Ohio.
The decrease in the cost of medication per vial in both the originator and biosimilar is an important finding in light of cost containment strategies, although Dr. Horst pointed out that the study didn’t determine if there were any savings to patients. “That is what clinicians and patients care about the most. I worry that while these savings were seen at insurance and health care organizational levels, patients may not have experienced any cost savings, and this is something we need to consider in the future,” she said.
The FDA created the biosimilar regulatory pathway in 2010 in an effort to reduce costs. “And they have. The cost savings however, has not directly translated to the individual patient in their copays or necessarily in changes to access when prescribing. Nor has it allowed dose escalation more easily, which is frequently needed,” said David T. Rubin, MD, AGAF, who was asked for comment.
Although the changes in prescribing patterns may reflect cost savings to patients, there are some limits to this interpretation, according to Dr. Rubin, of the University of Chicago. Payers are often the ones who determine a switch to biosimilar. The study also does not account for disease activity or phenotype, which can be an important confounder. Newer biologics that have come on to the market in recent years may also have affected the prescribing patterns for infliximab.
Nevertheless, an association between introduction of biosimilars and declining cost in the originator product (Remicade) is welcome, according to Dr. Rubin. “This is nice to see and we have seen it in our practices,” he said.
Unfortunately, “it has also not been seen to translate into reduced costs for patients nor has it been associated with increased access or changes in payer policies to allow these drugs to be used, or dose escalations to occur,” Dr. Rubin added.
Dr. Paglinco and Mr. Goldman have no relevant financial disclosures. Dr. Horst has consulted for Janssen, Takeda, Bristol-Myers Squibb, and Abbvie. Dr. Rubin has received grant support from Takeda and has consulted for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.
LAS VEGAS — , according to two new retrospective analyses that separately looked at private insurance and Medicare patients.
“It is interesting to see that biosimilar use is increasing in patients with Medicare insurance in the U.S. since introduction into the market. This shows that clinicians are getting more comfortable with their use in clinical practice,” said Sara Horst, MD, associate professor of gastroenterology, hepatology, and nutrition at Vanderbilt University Medical Center in Nashville, Tennessee. That “is a continued important question in use, especially in the older population,” Dr. Horst said at the poster session where the two studies were presented, at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
One study examined Medicare part D participants. The researchers included infliximab prescriptions between 2013 and 2021, with a break in 2017 when biosimilars were first introduced. Between 2013 and 2017, there was a 93.7% annual increase in infliximab cost, and a 29.0% increase in annual claims. Between 2017 and 2021, those numbers declined to 23.9% and 12.1%, respectively. The researchers also examined trends by individual states and found a wide range of results. “Nationwide, it seems to be doing exactly what you’d expect, and I’d say it’s encouraging. This is exactly what you want with the introduction of biosimilars, and this is what you want for the patient population. But there are some states that have not really kept up with the rest of the country, and may need to look further into what types of trends are there,” said Modan Goldman, who presented the study. He is a medical student at Carle Illinois College of Medicine in Urbana, Illinois.
The other study looked at use of infliximab versus a biosimilar between 2015 and 2021 in 42,009 patients 64 or younger, drawing data from Merative Marketscan Commercial Claims and Encounters Database. They excluded government-funded insurance. Between January 2015 and December 2017, the cost of a vial of infliximab increased by $6.31 per month, reaching a maxim cost of $1,491 per vial. In January 2018, the cost decreased by $62 per vial, with a downward trend after that of $12.93 per vial per month.
“[Getting] access to these drugs, especially for pediatric IBD, has been an uphill battle with insurance companies and getting the medication and the doses we want,” said Samantha Paglinco, DO, who presented the Marketscan study.
The findings demonstrated clear cost reductions. “At the beginning of our period, infliximab originator Remicade was a little over $1,200 per vial, and at the end of our period of 2021, we expected it to be around $1,800 per vial. However, with the introduction of multiple infliximab biosimilars, we did see it come down to $800 per vial, which generated a savings of $1,000, which is pretty significant. We’re hoping that by generating overall cost savings to insurance companies, this will allow for greater access, because we know infliximab is such a good medication for pediatric IBD and for many other autoimmune conditions,” said Dr. Paglinco, a pediatric GI fellow at Nationwide Children’s Hospital in Columbus, Ohio.
The decrease in the cost of medication per vial in both the originator and biosimilar is an important finding in light of cost containment strategies, although Dr. Horst pointed out that the study didn’t determine if there were any savings to patients. “That is what clinicians and patients care about the most. I worry that while these savings were seen at insurance and health care organizational levels, patients may not have experienced any cost savings, and this is something we need to consider in the future,” she said.
The FDA created the biosimilar regulatory pathway in 2010 in an effort to reduce costs. “And they have. The cost savings however, has not directly translated to the individual patient in their copays or necessarily in changes to access when prescribing. Nor has it allowed dose escalation more easily, which is frequently needed,” said David T. Rubin, MD, AGAF, who was asked for comment.
Although the changes in prescribing patterns may reflect cost savings to patients, there are some limits to this interpretation, according to Dr. Rubin, of the University of Chicago. Payers are often the ones who determine a switch to biosimilar. The study also does not account for disease activity or phenotype, which can be an important confounder. Newer biologics that have come on to the market in recent years may also have affected the prescribing patterns for infliximab.
Nevertheless, an association between introduction of biosimilars and declining cost in the originator product (Remicade) is welcome, according to Dr. Rubin. “This is nice to see and we have seen it in our practices,” he said.
Unfortunately, “it has also not been seen to translate into reduced costs for patients nor has it been associated with increased access or changes in payer policies to allow these drugs to be used, or dose escalations to occur,” Dr. Rubin added.
Dr. Paglinco and Mr. Goldman have no relevant financial disclosures. Dr. Horst has consulted for Janssen, Takeda, Bristol-Myers Squibb, and Abbvie. Dr. Rubin has received grant support from Takeda and has consulted for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.
LAS VEGAS — , according to two new retrospective analyses that separately looked at private insurance and Medicare patients.
“It is interesting to see that biosimilar use is increasing in patients with Medicare insurance in the U.S. since introduction into the market. This shows that clinicians are getting more comfortable with their use in clinical practice,” said Sara Horst, MD, associate professor of gastroenterology, hepatology, and nutrition at Vanderbilt University Medical Center in Nashville, Tennessee. That “is a continued important question in use, especially in the older population,” Dr. Horst said at the poster session where the two studies were presented, at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
One study examined Medicare part D participants. The researchers included infliximab prescriptions between 2013 and 2021, with a break in 2017 when biosimilars were first introduced. Between 2013 and 2017, there was a 93.7% annual increase in infliximab cost, and a 29.0% increase in annual claims. Between 2017 and 2021, those numbers declined to 23.9% and 12.1%, respectively. The researchers also examined trends by individual states and found a wide range of results. “Nationwide, it seems to be doing exactly what you’d expect, and I’d say it’s encouraging. This is exactly what you want with the introduction of biosimilars, and this is what you want for the patient population. But there are some states that have not really kept up with the rest of the country, and may need to look further into what types of trends are there,” said Modan Goldman, who presented the study. He is a medical student at Carle Illinois College of Medicine in Urbana, Illinois.
The other study looked at use of infliximab versus a biosimilar between 2015 and 2021 in 42,009 patients 64 or younger, drawing data from Merative Marketscan Commercial Claims and Encounters Database. They excluded government-funded insurance. Between January 2015 and December 2017, the cost of a vial of infliximab increased by $6.31 per month, reaching a maxim cost of $1,491 per vial. In January 2018, the cost decreased by $62 per vial, with a downward trend after that of $12.93 per vial per month.
“[Getting] access to these drugs, especially for pediatric IBD, has been an uphill battle with insurance companies and getting the medication and the doses we want,” said Samantha Paglinco, DO, who presented the Marketscan study.
The findings demonstrated clear cost reductions. “At the beginning of our period, infliximab originator Remicade was a little over $1,200 per vial, and at the end of our period of 2021, we expected it to be around $1,800 per vial. However, with the introduction of multiple infliximab biosimilars, we did see it come down to $800 per vial, which generated a savings of $1,000, which is pretty significant. We’re hoping that by generating overall cost savings to insurance companies, this will allow for greater access, because we know infliximab is such a good medication for pediatric IBD and for many other autoimmune conditions,” said Dr. Paglinco, a pediatric GI fellow at Nationwide Children’s Hospital in Columbus, Ohio.
The decrease in the cost of medication per vial in both the originator and biosimilar is an important finding in light of cost containment strategies, although Dr. Horst pointed out that the study didn’t determine if there were any savings to patients. “That is what clinicians and patients care about the most. I worry that while these savings were seen at insurance and health care organizational levels, patients may not have experienced any cost savings, and this is something we need to consider in the future,” she said.
The FDA created the biosimilar regulatory pathway in 2010 in an effort to reduce costs. “And they have. The cost savings however, has not directly translated to the individual patient in their copays or necessarily in changes to access when prescribing. Nor has it allowed dose escalation more easily, which is frequently needed,” said David T. Rubin, MD, AGAF, who was asked for comment.
Although the changes in prescribing patterns may reflect cost savings to patients, there are some limits to this interpretation, according to Dr. Rubin, of the University of Chicago. Payers are often the ones who determine a switch to biosimilar. The study also does not account for disease activity or phenotype, which can be an important confounder. Newer biologics that have come on to the market in recent years may also have affected the prescribing patterns for infliximab.
Nevertheless, an association between introduction of biosimilars and declining cost in the originator product (Remicade) is welcome, according to Dr. Rubin. “This is nice to see and we have seen it in our practices,” he said.
Unfortunately, “it has also not been seen to translate into reduced costs for patients nor has it been associated with increased access or changes in payer policies to allow these drugs to be used, or dose escalations to occur,” Dr. Rubin added.
Dr. Paglinco and Mr. Goldman have no relevant financial disclosures. Dr. Horst has consulted for Janssen, Takeda, Bristol-Myers Squibb, and Abbvie. Dr. Rubin has received grant support from Takeda and has consulted for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.
FROM CROHN’S AND COLITIS CONGRESS
In Refractory IBD, Combination Therapies Appear Safe, Effective
LAS VEGAS — . The study updates a meta-analysis published in 2022, which included 13 studies. The new work included 23 studies that looked at 8 different combinations.
There is a potential concern that the high adverse event rates seen in biologics could be compounded when they are used in combination, according to Ali Osman, MD, who presented the results at a poster session at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Theoretically, you should have more side effects or more serious side effects, but interestingly we didn’t find major side effects. I think the key message is that the combinations of biologic agents are promising in terms of efficacy. In terms of adverse events, it doesn’t lead to major adverse events,” said Dr. Osman, an instructor at Washington University School of Medicine in St. Louis.
Although the study did not directly compare the combinations, it did find potential differences in efficacy. “Our most effective [combination] in terms of response and remission was a combination of ustekinumab and an anti-TNF agent with a combined rate of 81.6%. Our lowest adverse events rate were [with the combination of] tofacitinib and vedolizumab,” said Dr. Osman.
The research is a useful update, according to David T. Rubin, MD, AGAF, who was asked for comment. “This has been explored before, but this is a nice effort to describe and try to compare studies of combination biological therapies or biologicals combined with [the JAK inhibitor]. This is to further explore the efforts being made to break the therapeutic ceiling by combining mechanisms, treat IBD and extra-intestinal manifestations with multiple agents simultaneously, and to explore novel treatment strategies,” said Dr. Rubin, professor of medicine and director of the Inflammatory Bowel Disease Center at University of Chicago Medicine.
He noted that the meta-analysis is limited by heterogeneity among the studies, many of which were case series that had been re-analyzed. The update included some prospective proof-of-concept studies of interest that were not in the earlier meta-analysis, including VEGA (anti-IL13 guselkumab plus anti-TNF golimumab versus either drug alone), and EXPLORER (vedolizumab, adalimumab, methotrexate), as well as a study of infliximab combined with natalizumab.
“We await the ongoing prospective trials of dual targeted therapies and novel designs for a future that will undoubtedly include thoughtful and rational combinations,” said Dr. Rubin.
The review included 23 studies that had a minimum of two patients who were treated with a combination of two biologics or a biologic and tofacitinib. The biologics included the anti-TNF antibodies adalimumab, certolizumab pegol, golimumab, and infliximab; as well as guselkumab, natalizumab, ustekinumab, and vedolizumab. Overall, the studies included 531 patients who underwent 543 therapeutic trials, using 8 different combinations.
The highest pooled clinical response observed was 81.6% with ustekinumab combined with an anti-TNF agent (P = .04, 9 studies, 44 therapeutic trials), which also had the highest remission rate of 64.2% (P = .03).
For the treatment of Crohn’s disease, the highest pooled clinical response and remission rates were also seen with ustekinumab combined with an anti-TNF agent (8 studies, 29 therapeutic trials), at 91.6% (P = .28). In ulcerative colitis, vedolizumab plus ustekinumab had the highest pooled clinical response rate at 100.0% (P = 1.00; 4 studies, 4 treatment trials) and ustekinumab plus an anti-TNF agent F at 100.0% (P = 1.00; 4 studies, 5 treatment trials).
Tofacitinib combined with vedolizumab had the lower adverse event rate (12.5%; P = .10; 8 studies, 76 treatment trials) followed by ustekinumab and an anti-TNF agent (12.7%; P = .08; 9 studies, 43 treatment trials) and tofacitinib plus anti-TNF (13.0%; 6 studies, 27 treatment trials).
Other combinations included guselkumab plus ant-TNF (1 study; clinical response, 69.0%), natalizumab plus an anti-TNF agent (1 study, clinical response, 36.5%), tofacitinib plus an anti-TNF agent (5 studies, clinical response, 71.6%), tofacitinib plus ustekinumab (5 studies, clinical response, 70.8%), tofacitinib plus vedolizumab (8 studies, clinical response, 52.7%), vedolizumab plus an anti-TNF agent (13 studies, clinical response, 62.8%), and vedolizumab plus ustekinumab (12 studies, clinical response, 79.3%).
Dr. Osman has no relevant financial conflicts of interest. Dr. Rubin has received grant support from Takeda, and has served as a consultant for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.
LAS VEGAS — . The study updates a meta-analysis published in 2022, which included 13 studies. The new work included 23 studies that looked at 8 different combinations.
There is a potential concern that the high adverse event rates seen in biologics could be compounded when they are used in combination, according to Ali Osman, MD, who presented the results at a poster session at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Theoretically, you should have more side effects or more serious side effects, but interestingly we didn’t find major side effects. I think the key message is that the combinations of biologic agents are promising in terms of efficacy. In terms of adverse events, it doesn’t lead to major adverse events,” said Dr. Osman, an instructor at Washington University School of Medicine in St. Louis.
Although the study did not directly compare the combinations, it did find potential differences in efficacy. “Our most effective [combination] in terms of response and remission was a combination of ustekinumab and an anti-TNF agent with a combined rate of 81.6%. Our lowest adverse events rate were [with the combination of] tofacitinib and vedolizumab,” said Dr. Osman.
The research is a useful update, according to David T. Rubin, MD, AGAF, who was asked for comment. “This has been explored before, but this is a nice effort to describe and try to compare studies of combination biological therapies or biologicals combined with [the JAK inhibitor]. This is to further explore the efforts being made to break the therapeutic ceiling by combining mechanisms, treat IBD and extra-intestinal manifestations with multiple agents simultaneously, and to explore novel treatment strategies,” said Dr. Rubin, professor of medicine and director of the Inflammatory Bowel Disease Center at University of Chicago Medicine.
He noted that the meta-analysis is limited by heterogeneity among the studies, many of which were case series that had been re-analyzed. The update included some prospective proof-of-concept studies of interest that were not in the earlier meta-analysis, including VEGA (anti-IL13 guselkumab plus anti-TNF golimumab versus either drug alone), and EXPLORER (vedolizumab, adalimumab, methotrexate), as well as a study of infliximab combined with natalizumab.
“We await the ongoing prospective trials of dual targeted therapies and novel designs for a future that will undoubtedly include thoughtful and rational combinations,” said Dr. Rubin.
The review included 23 studies that had a minimum of two patients who were treated with a combination of two biologics or a biologic and tofacitinib. The biologics included the anti-TNF antibodies adalimumab, certolizumab pegol, golimumab, and infliximab; as well as guselkumab, natalizumab, ustekinumab, and vedolizumab. Overall, the studies included 531 patients who underwent 543 therapeutic trials, using 8 different combinations.
The highest pooled clinical response observed was 81.6% with ustekinumab combined with an anti-TNF agent (P = .04, 9 studies, 44 therapeutic trials), which also had the highest remission rate of 64.2% (P = .03).
For the treatment of Crohn’s disease, the highest pooled clinical response and remission rates were also seen with ustekinumab combined with an anti-TNF agent (8 studies, 29 therapeutic trials), at 91.6% (P = .28). In ulcerative colitis, vedolizumab plus ustekinumab had the highest pooled clinical response rate at 100.0% (P = 1.00; 4 studies, 4 treatment trials) and ustekinumab plus an anti-TNF agent F at 100.0% (P = 1.00; 4 studies, 5 treatment trials).
Tofacitinib combined with vedolizumab had the lower adverse event rate (12.5%; P = .10; 8 studies, 76 treatment trials) followed by ustekinumab and an anti-TNF agent (12.7%; P = .08; 9 studies, 43 treatment trials) and tofacitinib plus anti-TNF (13.0%; 6 studies, 27 treatment trials).
Other combinations included guselkumab plus ant-TNF (1 study; clinical response, 69.0%), natalizumab plus an anti-TNF agent (1 study, clinical response, 36.5%), tofacitinib plus an anti-TNF agent (5 studies, clinical response, 71.6%), tofacitinib plus ustekinumab (5 studies, clinical response, 70.8%), tofacitinib plus vedolizumab (8 studies, clinical response, 52.7%), vedolizumab plus an anti-TNF agent (13 studies, clinical response, 62.8%), and vedolizumab plus ustekinumab (12 studies, clinical response, 79.3%).
Dr. Osman has no relevant financial conflicts of interest. Dr. Rubin has received grant support from Takeda, and has served as a consultant for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.
LAS VEGAS — . The study updates a meta-analysis published in 2022, which included 13 studies. The new work included 23 studies that looked at 8 different combinations.
There is a potential concern that the high adverse event rates seen in biologics could be compounded when they are used in combination, according to Ali Osman, MD, who presented the results at a poster session at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Theoretically, you should have more side effects or more serious side effects, but interestingly we didn’t find major side effects. I think the key message is that the combinations of biologic agents are promising in terms of efficacy. In terms of adverse events, it doesn’t lead to major adverse events,” said Dr. Osman, an instructor at Washington University School of Medicine in St. Louis.
Although the study did not directly compare the combinations, it did find potential differences in efficacy. “Our most effective [combination] in terms of response and remission was a combination of ustekinumab and an anti-TNF agent with a combined rate of 81.6%. Our lowest adverse events rate were [with the combination of] tofacitinib and vedolizumab,” said Dr. Osman.
The research is a useful update, according to David T. Rubin, MD, AGAF, who was asked for comment. “This has been explored before, but this is a nice effort to describe and try to compare studies of combination biological therapies or biologicals combined with [the JAK inhibitor]. This is to further explore the efforts being made to break the therapeutic ceiling by combining mechanisms, treat IBD and extra-intestinal manifestations with multiple agents simultaneously, and to explore novel treatment strategies,” said Dr. Rubin, professor of medicine and director of the Inflammatory Bowel Disease Center at University of Chicago Medicine.
He noted that the meta-analysis is limited by heterogeneity among the studies, many of which were case series that had been re-analyzed. The update included some prospective proof-of-concept studies of interest that were not in the earlier meta-analysis, including VEGA (anti-IL13 guselkumab plus anti-TNF golimumab versus either drug alone), and EXPLORER (vedolizumab, adalimumab, methotrexate), as well as a study of infliximab combined with natalizumab.
“We await the ongoing prospective trials of dual targeted therapies and novel designs for a future that will undoubtedly include thoughtful and rational combinations,” said Dr. Rubin.
The review included 23 studies that had a minimum of two patients who were treated with a combination of two biologics or a biologic and tofacitinib. The biologics included the anti-TNF antibodies adalimumab, certolizumab pegol, golimumab, and infliximab; as well as guselkumab, natalizumab, ustekinumab, and vedolizumab. Overall, the studies included 531 patients who underwent 543 therapeutic trials, using 8 different combinations.
The highest pooled clinical response observed was 81.6% with ustekinumab combined with an anti-TNF agent (P = .04, 9 studies, 44 therapeutic trials), which also had the highest remission rate of 64.2% (P = .03).
For the treatment of Crohn’s disease, the highest pooled clinical response and remission rates were also seen with ustekinumab combined with an anti-TNF agent (8 studies, 29 therapeutic trials), at 91.6% (P = .28). In ulcerative colitis, vedolizumab plus ustekinumab had the highest pooled clinical response rate at 100.0% (P = 1.00; 4 studies, 4 treatment trials) and ustekinumab plus an anti-TNF agent F at 100.0% (P = 1.00; 4 studies, 5 treatment trials).
Tofacitinib combined with vedolizumab had the lower adverse event rate (12.5%; P = .10; 8 studies, 76 treatment trials) followed by ustekinumab and an anti-TNF agent (12.7%; P = .08; 9 studies, 43 treatment trials) and tofacitinib plus anti-TNF (13.0%; 6 studies, 27 treatment trials).
Other combinations included guselkumab plus ant-TNF (1 study; clinical response, 69.0%), natalizumab plus an anti-TNF agent (1 study, clinical response, 36.5%), tofacitinib plus an anti-TNF agent (5 studies, clinical response, 71.6%), tofacitinib plus ustekinumab (5 studies, clinical response, 70.8%), tofacitinib plus vedolizumab (8 studies, clinical response, 52.7%), vedolizumab plus an anti-TNF agent (13 studies, clinical response, 62.8%), and vedolizumab plus ustekinumab (12 studies, clinical response, 79.3%).
Dr. Osman has no relevant financial conflicts of interest. Dr. Rubin has received grant support from Takeda, and has served as a consultant for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.
FROM CROHN’S & COLITIS CONGRESS
Cell-Free DNA May Inform IBD Diagnosis
LAS VEGAS —
“We think for indeterminate colitis, our assay can be quite beneficial in helping a clinician resolve or provide some additional insight and information. We have a very robust ability to predict from just the plasma microbial cell free DNA alone [whether] individuals are in remission or mild or moderate or active disease,” Shiv Kale, PhD, said during a presentation of the results at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. Dr. Kale is director of computational biomarker discovery at Karius Inc., a company whose Karius Test is also being developed as a rapid test for various infections and febrile neutropenia.
cfDNA has proved to be a useful biomarker for a range of conditions, including cancer screening, diagnosis and monitoring, prenatal testing, and organ monitoring following transplantation. The tests rely on the fact that both human and microbial cells release DNA after cell death, and it is readily detectable in plasma.
Dr. Kale described the company’s efforts to identify microbial species biomarkers and a classification scheme that he said leads to consistent performance.
The latest study included 196 patients with Crohn’s disease and 196 with ulcerative colitis, with each group including individuals in remission and with mild, moderate, and severe disease. All patients had an endoscopic assessment within 30 days of plasma measurements.
cfDNA distinguished between patients with Crohn’s disease, ulcerative colitis, and those who were asymptomatic. It distinguished between patients with IBD and those who were asymptomatic with a sensitivity of 99.5% and a specificity of 90%, which are equivalent to or better than other traditional measures to distinguish active IBD versus asymptomatic patients.
The researchers plan a follow-up study of 1,800 samples in partnership with the Crohn’s and Colitis Foundation to examine the ability of cfDNA to determine disease severity, as well as location of disease and Crohn’s disease subtypes.
An ‘Intriguing’ Method
During the Q&A session, one questioner pointed out that colorectal cancer and infections can produce microbial signatures that could be confounding the results. He asked: “Do you have a data set to compare [cfDNA findings] to serum from C. diff, norovirus, and colorectal cancer? And if you don’t, I strongly encourage you to do so.” Dr. Kale responded that the group is working on that.
Asked for comment, session moderator Dana Lukin, MD, AGAF, offered praise for the work.
“I think it’s an intriguing method that we haven’t seen used as a predictor in IBD. Using this as a biomarker of disease type is very intriguing for confirming a diagnosis. I think probably one of the most compelling points is the distinction between IBD and non-IBD. Our current serologic-based assays do not really do that very well. I think this is a big improvement on that,” said Dr. Lukin, associate professor of clinical medicine at Weill Cornell Medical College, New York.
He echoed the questioner’s comments, suggesting that a key question will be whether cfDNA can correlate with disease activity over time.
He also called for prospective studies to validate the approach.
If successful, the technology could have broad application. “Certainly in kids this might be useful or in folks that either aren’t as inclined to have invasive testing done, or for whatever logistic reasons it’s not easy,” said Dr. Lukin.
Dr. Kale is an employee of Karius. Dr. Lukin has no relevant financial disclosures..
LAS VEGAS —
“We think for indeterminate colitis, our assay can be quite beneficial in helping a clinician resolve or provide some additional insight and information. We have a very robust ability to predict from just the plasma microbial cell free DNA alone [whether] individuals are in remission or mild or moderate or active disease,” Shiv Kale, PhD, said during a presentation of the results at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. Dr. Kale is director of computational biomarker discovery at Karius Inc., a company whose Karius Test is also being developed as a rapid test for various infections and febrile neutropenia.
cfDNA has proved to be a useful biomarker for a range of conditions, including cancer screening, diagnosis and monitoring, prenatal testing, and organ monitoring following transplantation. The tests rely on the fact that both human and microbial cells release DNA after cell death, and it is readily detectable in plasma.
Dr. Kale described the company’s efforts to identify microbial species biomarkers and a classification scheme that he said leads to consistent performance.
The latest study included 196 patients with Crohn’s disease and 196 with ulcerative colitis, with each group including individuals in remission and with mild, moderate, and severe disease. All patients had an endoscopic assessment within 30 days of plasma measurements.
cfDNA distinguished between patients with Crohn’s disease, ulcerative colitis, and those who were asymptomatic. It distinguished between patients with IBD and those who were asymptomatic with a sensitivity of 99.5% and a specificity of 90%, which are equivalent to or better than other traditional measures to distinguish active IBD versus asymptomatic patients.
The researchers plan a follow-up study of 1,800 samples in partnership with the Crohn’s and Colitis Foundation to examine the ability of cfDNA to determine disease severity, as well as location of disease and Crohn’s disease subtypes.
An ‘Intriguing’ Method
During the Q&A session, one questioner pointed out that colorectal cancer and infections can produce microbial signatures that could be confounding the results. He asked: “Do you have a data set to compare [cfDNA findings] to serum from C. diff, norovirus, and colorectal cancer? And if you don’t, I strongly encourage you to do so.” Dr. Kale responded that the group is working on that.
Asked for comment, session moderator Dana Lukin, MD, AGAF, offered praise for the work.
“I think it’s an intriguing method that we haven’t seen used as a predictor in IBD. Using this as a biomarker of disease type is very intriguing for confirming a diagnosis. I think probably one of the most compelling points is the distinction between IBD and non-IBD. Our current serologic-based assays do not really do that very well. I think this is a big improvement on that,” said Dr. Lukin, associate professor of clinical medicine at Weill Cornell Medical College, New York.
He echoed the questioner’s comments, suggesting that a key question will be whether cfDNA can correlate with disease activity over time.
He also called for prospective studies to validate the approach.
If successful, the technology could have broad application. “Certainly in kids this might be useful or in folks that either aren’t as inclined to have invasive testing done, or for whatever logistic reasons it’s not easy,” said Dr. Lukin.
Dr. Kale is an employee of Karius. Dr. Lukin has no relevant financial disclosures..
LAS VEGAS —
“We think for indeterminate colitis, our assay can be quite beneficial in helping a clinician resolve or provide some additional insight and information. We have a very robust ability to predict from just the plasma microbial cell free DNA alone [whether] individuals are in remission or mild or moderate or active disease,” Shiv Kale, PhD, said during a presentation of the results at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. Dr. Kale is director of computational biomarker discovery at Karius Inc., a company whose Karius Test is also being developed as a rapid test for various infections and febrile neutropenia.
cfDNA has proved to be a useful biomarker for a range of conditions, including cancer screening, diagnosis and monitoring, prenatal testing, and organ monitoring following transplantation. The tests rely on the fact that both human and microbial cells release DNA after cell death, and it is readily detectable in plasma.
Dr. Kale described the company’s efforts to identify microbial species biomarkers and a classification scheme that he said leads to consistent performance.
The latest study included 196 patients with Crohn’s disease and 196 with ulcerative colitis, with each group including individuals in remission and with mild, moderate, and severe disease. All patients had an endoscopic assessment within 30 days of plasma measurements.
cfDNA distinguished between patients with Crohn’s disease, ulcerative colitis, and those who were asymptomatic. It distinguished between patients with IBD and those who were asymptomatic with a sensitivity of 99.5% and a specificity of 90%, which are equivalent to or better than other traditional measures to distinguish active IBD versus asymptomatic patients.
The researchers plan a follow-up study of 1,800 samples in partnership with the Crohn’s and Colitis Foundation to examine the ability of cfDNA to determine disease severity, as well as location of disease and Crohn’s disease subtypes.
An ‘Intriguing’ Method
During the Q&A session, one questioner pointed out that colorectal cancer and infections can produce microbial signatures that could be confounding the results. He asked: “Do you have a data set to compare [cfDNA findings] to serum from C. diff, norovirus, and colorectal cancer? And if you don’t, I strongly encourage you to do so.” Dr. Kale responded that the group is working on that.
Asked for comment, session moderator Dana Lukin, MD, AGAF, offered praise for the work.
“I think it’s an intriguing method that we haven’t seen used as a predictor in IBD. Using this as a biomarker of disease type is very intriguing for confirming a diagnosis. I think probably one of the most compelling points is the distinction between IBD and non-IBD. Our current serologic-based assays do not really do that very well. I think this is a big improvement on that,” said Dr. Lukin, associate professor of clinical medicine at Weill Cornell Medical College, New York.
He echoed the questioner’s comments, suggesting that a key question will be whether cfDNA can correlate with disease activity over time.
He also called for prospective studies to validate the approach.
If successful, the technology could have broad application. “Certainly in kids this might be useful or in folks that either aren’t as inclined to have invasive testing done, or for whatever logistic reasons it’s not easy,” said Dr. Lukin.
Dr. Kale is an employee of Karius. Dr. Lukin has no relevant financial disclosures..
FROM CROHN’S AND COLITIS CONGRESS
Wearable Device Tracks IBD from Sweat
LAS VEGAS —
The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.
Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.
The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.
The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.
The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.
The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.
A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.
The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.
The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.
There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.
Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
Treating to Target
The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.
He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.
If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.
Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.
LAS VEGAS —
The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.
Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.
The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.
The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.
The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.
The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.
A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.
The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.
The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.
There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.
Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
Treating to Target
The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.
He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.
If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.
Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.
LAS VEGAS —
The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.
Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.
The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.
The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.
The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.
The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.
A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.
The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.
The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.
There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.
Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
Treating to Target
The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.
He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.
If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.
Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.
FROM CROHN’S & COLITIS CONGRESS