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Weight gain may exacerbate structural damage in knee OA
researchers reported at the OARSI 2022 World Congress.
Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)
Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.
Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).
Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).
Importance of weight change in OA
“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.
“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”
He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
Why look at weight change effects in OA?
“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.
Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.
The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.
“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.
Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.
The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.
“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”
Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”
There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.
Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.
“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”
The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.
researchers reported at the OARSI 2022 World Congress.
Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)
Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.
Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).
Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).
Importance of weight change in OA
“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.
“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”
He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
Why look at weight change effects in OA?
“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.
Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.
The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.
“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.
Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.
The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.
“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”
Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”
There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.
Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.
“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”
The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.
researchers reported at the OARSI 2022 World Congress.
Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)
Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.
Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).
Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).
Importance of weight change in OA
“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.
“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”
He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
Why look at weight change effects in OA?
“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.
Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.
The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.
“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.
Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.
The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.
“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”
Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”
There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.
Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.
“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”
The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.
FROM OARSI 2022
High comorbidity rate seen before osteoarthritis diagnosis
presented at the OARSI 2022 World Congress.
“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.
“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.
The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
Comorbidity and OA
One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.
“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.
“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.
While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.
“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.
Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
Results and perspective
Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.
Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.
Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.
“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.
“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”
One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.
“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.
“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.
The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
presented at the OARSI 2022 World Congress.
“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.
“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.
The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
Comorbidity and OA
One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.
“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.
“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.
While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.
“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.
Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
Results and perspective
Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.
Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.
Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.
“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.
“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”
One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.
“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.
“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.
The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
presented at the OARSI 2022 World Congress.
“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.
“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.
The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
Comorbidity and OA
One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.
“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.
“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.
While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.
“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.
Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
Results and perspective
Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.
Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.
Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.
“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.
“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”
One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.
“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.
“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.
The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
FROM OARSI 2022
Early meniscal surgery on par with active rehab in under 40s
according to the results of the randomized controlled DREAM trial presented at the OARSI 2022 World Congress.
Indeed, similar clinically relevant improvements in knee pain, function, and quality of life at 12 months were seen among participants in both study arms.
“Our results highlight that decisions on surgery or nonsurgical treatment must depend on preferences and values and needs of the individuals consulting their surgeon,” Søren T. Skou, PT, MSc, PhD, reported during one of the opening sessions at the meeting sponsored by the Osteoarthritis Research Society International.
The lack of superiority was contrary to the expectations of the researchers who hypothesized that early surgical intervention in adults aged between 18 and 40 years would be more beneficial than an active rehabilitation program with later surgery if needed.
Although the results do tie in with the results of other trials and systematic reviews in older adults the reason for looking at young adults specifically, aside from the obvious differences and the origin of meniscal tears, was that no study had previously looked at this population, Dr. Skou explained.
Assembling the DREAM team
The DREAM (Danish RCT on Exercise versus Arthroscopic Meniscal Surgery for Young Adults) trial “was a collaborative effort among many clinicians in Denmark – physical therapists, exercise physiologists, and surgeons,” Dr. Skou observed.
In total, 121 adults with MRI-verified meniscal tears who were eligible for surgery were recruited and randomized to either the early meniscal surgery group (n = 60) or to the exercise and education group (n = 61). The mean age was just below 30 years and 28% were female
Meniscal surgery, which was either an arthroscopic partial meniscectomy or meniscal repair, was performed at seven specialist centers. The exercise and education program was delivered by trained physical therapists working at 19 participating centers. The latter consisted of 24 sessions of group-based exercise therapy and education held over a period of 12 weeks.
Participants randomized to the exercise and education arm had the option of later meniscal surgery, with one in four eventually undergoing this procedure.
No gain in pain
The primary outcome measure was the difference in the mean of four of the subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) from baseline to 12-month assessment. The KOOS4 looks at knee pain, symptoms, function in sport and recreation, and quality of life.
“We considered a 10-point difference between groups as clinically relevant,” said Dr. Skou, but “adjusting for the baseline differences, we found no [statistical] differences or clinically relevant differences between groups.”
Improvement was seen in both groups. In an intention-to-treat analysis the KOOS4 scores improved by 19.2 points and 16.4 points respectively in the surgery and exercise and education groups, with a mean adjusted difference of 5.4 (95% confidence interval, –0.7 to 11.4). There was also no difference in a per protocol analysis, which considered only those participants who received the treatment strategy they were allocated (mean adjusted difference, 5.7; 95% CI, –0.9 to 12.4).
Secondary outcomes were also similarly improved in both groups with clinically relevant increases in all four KOOS subscale scores and in the Western Ontario Meniscal Evaluation Tool (WOMET).
While there were some statistical differences between the groups, such as better KOOS pain, symptoms, and WOMET scores in the surgery group, these were felt unlikely to be clinically relevant. Likewise, there was a statistically greater improvement in muscle strength in the exercise and education group than surgery group.
There was no statistical difference in the number of serious adverse events, including worsening of symptoms with or without acute onset during activity and lateral meniscal cysts, with four reported in the surgical group and seven in the exercise and education group.
Views on results
The results of the trial, published in NEJM Evidence, garnered attention on Twitter with several physiotherapists noting the data were positive for the nonsurgical management of meniscal tears in younger adults.
During discussion at the meeting, Nadine Foster, PhD, NIHR Professor of Musculoskeletal Health in Primary Care at Keele (England) University, asked if a larger cohort might not swing the results in favor of surgery.
She said: “Congratulations on this trial. The challenge: Your 95% CIs suggest a larger trial would have concluded superiority of surgery?”
Dr. Skou responded: “Most likely the true difference is outside the clinically relevant difference, but obviously, we cannot exclude that there is actually a clinically relevant difference between groups.”
Martin Englund, MD, Phd, of Lund (Sweden) University Hospital in Sweden, pointed out that 16 patients in the exercise and education group had “crossed over” and undergone surgery. “Were there any differences for those patients?” he asked.
“We looked at whether there was a difference between those – obviously only having 16 participants, we’re not able to do any statistical comparisons – but looking just visually at the data, they seem to improve to the same extent as those undergoing nonsurgical only,” Dr. Skou said.
The 2-year MRI data are currently being examined and will “obviously also be very interesting,” he added.
The DREAM trial was funded by the Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, Spar Nord Foundation, Danish Rheumatism Association, Association of Danish Physiotherapists Research Fund, Research Council at Næstved-Slagelse-Ringsted Hospitals, and Region Zealand. Dr. Skou had no financial or other conflicts of interest to disclose.
according to the results of the randomized controlled DREAM trial presented at the OARSI 2022 World Congress.
Indeed, similar clinically relevant improvements in knee pain, function, and quality of life at 12 months were seen among participants in both study arms.
“Our results highlight that decisions on surgery or nonsurgical treatment must depend on preferences and values and needs of the individuals consulting their surgeon,” Søren T. Skou, PT, MSc, PhD, reported during one of the opening sessions at the meeting sponsored by the Osteoarthritis Research Society International.
The lack of superiority was contrary to the expectations of the researchers who hypothesized that early surgical intervention in adults aged between 18 and 40 years would be more beneficial than an active rehabilitation program with later surgery if needed.
Although the results do tie in with the results of other trials and systematic reviews in older adults the reason for looking at young adults specifically, aside from the obvious differences and the origin of meniscal tears, was that no study had previously looked at this population, Dr. Skou explained.
Assembling the DREAM team
The DREAM (Danish RCT on Exercise versus Arthroscopic Meniscal Surgery for Young Adults) trial “was a collaborative effort among many clinicians in Denmark – physical therapists, exercise physiologists, and surgeons,” Dr. Skou observed.
In total, 121 adults with MRI-verified meniscal tears who were eligible for surgery were recruited and randomized to either the early meniscal surgery group (n = 60) or to the exercise and education group (n = 61). The mean age was just below 30 years and 28% were female
Meniscal surgery, which was either an arthroscopic partial meniscectomy or meniscal repair, was performed at seven specialist centers. The exercise and education program was delivered by trained physical therapists working at 19 participating centers. The latter consisted of 24 sessions of group-based exercise therapy and education held over a period of 12 weeks.
Participants randomized to the exercise and education arm had the option of later meniscal surgery, with one in four eventually undergoing this procedure.
No gain in pain
The primary outcome measure was the difference in the mean of four of the subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) from baseline to 12-month assessment. The KOOS4 looks at knee pain, symptoms, function in sport and recreation, and quality of life.
“We considered a 10-point difference between groups as clinically relevant,” said Dr. Skou, but “adjusting for the baseline differences, we found no [statistical] differences or clinically relevant differences between groups.”
Improvement was seen in both groups. In an intention-to-treat analysis the KOOS4 scores improved by 19.2 points and 16.4 points respectively in the surgery and exercise and education groups, with a mean adjusted difference of 5.4 (95% confidence interval, –0.7 to 11.4). There was also no difference in a per protocol analysis, which considered only those participants who received the treatment strategy they were allocated (mean adjusted difference, 5.7; 95% CI, –0.9 to 12.4).
Secondary outcomes were also similarly improved in both groups with clinically relevant increases in all four KOOS subscale scores and in the Western Ontario Meniscal Evaluation Tool (WOMET).
While there were some statistical differences between the groups, such as better KOOS pain, symptoms, and WOMET scores in the surgery group, these were felt unlikely to be clinically relevant. Likewise, there was a statistically greater improvement in muscle strength in the exercise and education group than surgery group.
There was no statistical difference in the number of serious adverse events, including worsening of symptoms with or without acute onset during activity and lateral meniscal cysts, with four reported in the surgical group and seven in the exercise and education group.
Views on results
The results of the trial, published in NEJM Evidence, garnered attention on Twitter with several physiotherapists noting the data were positive for the nonsurgical management of meniscal tears in younger adults.
During discussion at the meeting, Nadine Foster, PhD, NIHR Professor of Musculoskeletal Health in Primary Care at Keele (England) University, asked if a larger cohort might not swing the results in favor of surgery.
She said: “Congratulations on this trial. The challenge: Your 95% CIs suggest a larger trial would have concluded superiority of surgery?”
Dr. Skou responded: “Most likely the true difference is outside the clinically relevant difference, but obviously, we cannot exclude that there is actually a clinically relevant difference between groups.”
Martin Englund, MD, Phd, of Lund (Sweden) University Hospital in Sweden, pointed out that 16 patients in the exercise and education group had “crossed over” and undergone surgery. “Were there any differences for those patients?” he asked.
“We looked at whether there was a difference between those – obviously only having 16 participants, we’re not able to do any statistical comparisons – but looking just visually at the data, they seem to improve to the same extent as those undergoing nonsurgical only,” Dr. Skou said.
The 2-year MRI data are currently being examined and will “obviously also be very interesting,” he added.
The DREAM trial was funded by the Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, Spar Nord Foundation, Danish Rheumatism Association, Association of Danish Physiotherapists Research Fund, Research Council at Næstved-Slagelse-Ringsted Hospitals, and Region Zealand. Dr. Skou had no financial or other conflicts of interest to disclose.
according to the results of the randomized controlled DREAM trial presented at the OARSI 2022 World Congress.
Indeed, similar clinically relevant improvements in knee pain, function, and quality of life at 12 months were seen among participants in both study arms.
“Our results highlight that decisions on surgery or nonsurgical treatment must depend on preferences and values and needs of the individuals consulting their surgeon,” Søren T. Skou, PT, MSc, PhD, reported during one of the opening sessions at the meeting sponsored by the Osteoarthritis Research Society International.
The lack of superiority was contrary to the expectations of the researchers who hypothesized that early surgical intervention in adults aged between 18 and 40 years would be more beneficial than an active rehabilitation program with later surgery if needed.
Although the results do tie in with the results of other trials and systematic reviews in older adults the reason for looking at young adults specifically, aside from the obvious differences and the origin of meniscal tears, was that no study had previously looked at this population, Dr. Skou explained.
Assembling the DREAM team
The DREAM (Danish RCT on Exercise versus Arthroscopic Meniscal Surgery for Young Adults) trial “was a collaborative effort among many clinicians in Denmark – physical therapists, exercise physiologists, and surgeons,” Dr. Skou observed.
In total, 121 adults with MRI-verified meniscal tears who were eligible for surgery were recruited and randomized to either the early meniscal surgery group (n = 60) or to the exercise and education group (n = 61). The mean age was just below 30 years and 28% were female
Meniscal surgery, which was either an arthroscopic partial meniscectomy or meniscal repair, was performed at seven specialist centers. The exercise and education program was delivered by trained physical therapists working at 19 participating centers. The latter consisted of 24 sessions of group-based exercise therapy and education held over a period of 12 weeks.
Participants randomized to the exercise and education arm had the option of later meniscal surgery, with one in four eventually undergoing this procedure.
No gain in pain
The primary outcome measure was the difference in the mean of four of the subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) from baseline to 12-month assessment. The KOOS4 looks at knee pain, symptoms, function in sport and recreation, and quality of life.
“We considered a 10-point difference between groups as clinically relevant,” said Dr. Skou, but “adjusting for the baseline differences, we found no [statistical] differences or clinically relevant differences between groups.”
Improvement was seen in both groups. In an intention-to-treat analysis the KOOS4 scores improved by 19.2 points and 16.4 points respectively in the surgery and exercise and education groups, with a mean adjusted difference of 5.4 (95% confidence interval, –0.7 to 11.4). There was also no difference in a per protocol analysis, which considered only those participants who received the treatment strategy they were allocated (mean adjusted difference, 5.7; 95% CI, –0.9 to 12.4).
Secondary outcomes were also similarly improved in both groups with clinically relevant increases in all four KOOS subscale scores and in the Western Ontario Meniscal Evaluation Tool (WOMET).
While there were some statistical differences between the groups, such as better KOOS pain, symptoms, and WOMET scores in the surgery group, these were felt unlikely to be clinically relevant. Likewise, there was a statistically greater improvement in muscle strength in the exercise and education group than surgery group.
There was no statistical difference in the number of serious adverse events, including worsening of symptoms with or without acute onset during activity and lateral meniscal cysts, with four reported in the surgical group and seven in the exercise and education group.
Views on results
The results of the trial, published in NEJM Evidence, garnered attention on Twitter with several physiotherapists noting the data were positive for the nonsurgical management of meniscal tears in younger adults.
During discussion at the meeting, Nadine Foster, PhD, NIHR Professor of Musculoskeletal Health in Primary Care at Keele (England) University, asked if a larger cohort might not swing the results in favor of surgery.
She said: “Congratulations on this trial. The challenge: Your 95% CIs suggest a larger trial would have concluded superiority of surgery?”
Dr. Skou responded: “Most likely the true difference is outside the clinically relevant difference, but obviously, we cannot exclude that there is actually a clinically relevant difference between groups.”
Martin Englund, MD, Phd, of Lund (Sweden) University Hospital in Sweden, pointed out that 16 patients in the exercise and education group had “crossed over” and undergone surgery. “Were there any differences for those patients?” he asked.
“We looked at whether there was a difference between those – obviously only having 16 participants, we’re not able to do any statistical comparisons – but looking just visually at the data, they seem to improve to the same extent as those undergoing nonsurgical only,” Dr. Skou said.
The 2-year MRI data are currently being examined and will “obviously also be very interesting,” he added.
The DREAM trial was funded by the Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, Spar Nord Foundation, Danish Rheumatism Association, Association of Danish Physiotherapists Research Fund, Research Council at Næstved-Slagelse-Ringsted Hospitals, and Region Zealand. Dr. Skou had no financial or other conflicts of interest to disclose.
FROM OARSI 2022
Artificial intelligence aids assessment of UC activity, remission
Not only are artificial intelligence (AI) systems potentially highly accurate for assessment of disease activity and remission of ulcerative colitis (UC), but they can mitigate some limits of human assessment, according to presentations at the 17th congress of the European Crohn’s and Colitis Organisation.
Importantly, AI systems have the potential to supplement the services of expert histopathologists and endoscopists rather than replace them, several experts asserted at the meeting.
“We will always need pathologists,” reassured inflammatory bowel disease (IBD) specialist Laurent Peyrin-Biroulet, MD, PhD, of Nancy (France) University Hospital, who presented about the use of an AI-driven scoring system to measure histological disease activity in UC.
Dr. Peyrin-Biroulet, who is the president of ECCO and acts as the scientific secretary of the International Organization for the Study of IBD, added that the use of AI systems could mean that pathologists have more time to do other tasks. Not only that, but it’s also not always possible to have IBD pathologist in every center, everywhere in the world.
“If we can get something that will automatically evaluate the disease activity, I think it will be something fantastic,” Dr. Peyrin-Biroulet said, “and it’s the reason why we were thinking that there is a need for an automated method to measure histological activity in UC.”
Old concept enhancing current practice
The idea of using AI systems to aid diagnostics is not new but now makes even more sense in the post–COVID-19 era, suggested Aaron F. Pollett, MD, MSc, FRCPC, codirector of the division of diagnostic medical genetics at Mount Sinai Hospital in Toronto and a pathologist with a specialty interest in gastrointestinal pathology.
“When we talk about artificial intelligence and histology, there’s actually a very long history, it goes back over 30 years,” Dr. Pollett said, from assessing cervical samples to its use in breast screening.
What seems to be sudden flurry of activity in the world of AI and pathology in recent years comes down to having a higher capacity for looking at large images, having access to large data sets, and having a high amount of computing power, Dr. Pollet inferred. Moreover, “the capacity and the need for whole slide imaging has really grown especially in the last few years as the pandemic has forced centers to adopt.” The need to work remotely and flexibly across centers and the number of available pathologists have also played a role.
AI systems that use image-based retrieval systems are making good headway in IBD, particularly in the diagnosis of UC where “some of the initial research is showing it can be quite good,” said Dr. Pollett. The “patchiness that Crohn’s can have in comparison to UC” means that it’s still an emerging area, but can perhaps be useful for more questionable cases in which “having that degree of certainty can certainly help because there is a discrepancy between specialist and nonspecialist pathologists in the likelihood that what they predict on the biopsy will be the underlying disease.”
AI systems in IBD – do they work?
Histopathology is becoming increasingly integrated into IBD clinical trial design at the behest of the Food and Drug Administration and European associations such as ECCO. This can be a tedious procedure that can be prone to error and disagreement between scorers.
The AI-driven scoring system that Dr. Peyrin-Biroulet and associates have been working on aims to fix all that by using machine learning and image processing to set up a reproducible system. Their system, which is based on the Nancy histological index for UC, shows high correlation (87%) with histopathologists’ assessment and was 100% accurate in identifying images with high (grade 4) or no (grade 0) inflammatory activity. The accuracy decreased, however, when trying to distinguish between more moderate activity, with a 75% accuracy for identifying grade 3 and 82% accuracy for grades 1 or 2.
“I’m actually very fascinated to see how we can be supported by the AI work in our practice,” observed Francesca Rosini, a histopathologist working at S. Orsola–Malpighi University Hospital in Bologna, Italy.
Dr. Rosini, who chaired the digital oral presentation session in which Dr. Peyrin-Biroulet had presented also noted that “obviously for us as well [as AI systems] no activity or severe activity is the easiest part but when it’s in between that’s where the problems come.”
Simplifying histological scoring
Simplifying scoring for use in AI systems could be the key to their future success, as Tommaso Lorenzo Parigi, MD, from Humanitas University in Milan, and a research fellow at the University of Birmingham (England), suggested.
“Histology is particularly important to distinguish between mild activity and remission,” Dr. Parigi said. “More than 30 histological scores that have been proposed, but their adoption in clinical practice remains limited.”
Dr. Parigi has been part of an international team that has developed a simplified histological score based on “the presence of absence of neutrophils, regardless of their number,” since these are “key determinants of disease activity”.
The score, known as the Paddington International Virtual Chromoendoscopy Scre (PICaSSO) Histologic Remission Index (PHRI), has been shown to correlate well with endoscopic outcomes and thus a good measure to include in AI systems. The results of this work were published online in Gut to coincide with the ECCO congress.
“We are getting close to a world where we could screen biopsies with this kind of systems and consider skipping the pathologists result if AI detected activity,” Dr. Parigi provocatively suggested. “Of course, we need to increase and improve our sensitivity, and we are currently working on that to reduce false negatives, as well as training our model to use and apply other histological scores.”
Assessing the gut in real time
Perhaps one of the most exciting developments it to be able to use these AI technologies to examine the gut in real time.
“Virtual chromoendoscopy will give you the opportunity to distinguish very carefully all the details of mucosal vascular pattern,” said Marietta Iacucci MD, PhD, FASGE, AGAF, an associate professor and gastroenterology consultant at the Birmingham (England) University Hospitals.
“So AI can give you, in real time, the score but at the same time it can help to target, to do biopsies for healing,” Dr. Iacucci added when reporting the results of a study evaluating the performance of the first virtual chromoendoscopy AI system to detect endoscopic and histologic remission in UC.
The system was proven to predict endoscopic remission very accurately (94% using PICaSSO and 87% using the UC endoscopic index of severity) when compared with a human endoscopist. Rates of predicting histological remission were also high, at around 83%-85%, depending on the score used.
“For the future, this AI tool can expediate, support, and standardize the endoscopic evaluation of UC mucosal healing in clinical practice and in clinical trials,” Dr. Iacucci said.
The next steps are to combine virtual chromoendoscopy with the PHRI and to validate the tool in a multicenter, international PICaSSO-AI study.
The AI-driven scoring system presented by Dr. Peyrin-Biroulet was supported by Takeda. Dr. Peryin-Biroulet acknowledged the receipt of personal fees and grants from Takeda along with multiple other Pharma companies and owning stock options from CTMA. Dr. Iacucci has received research grants from Pentax, AbbVie, Olympus, and Fujifilm and personal fees from Pentax, AbbVie and Janssen. Dr. Pollett, Dr. Rosini, and Dr. Parigi had no financial conflicts of interest to disclose.
Not only are artificial intelligence (AI) systems potentially highly accurate for assessment of disease activity and remission of ulcerative colitis (UC), but they can mitigate some limits of human assessment, according to presentations at the 17th congress of the European Crohn’s and Colitis Organisation.
Importantly, AI systems have the potential to supplement the services of expert histopathologists and endoscopists rather than replace them, several experts asserted at the meeting.
“We will always need pathologists,” reassured inflammatory bowel disease (IBD) specialist Laurent Peyrin-Biroulet, MD, PhD, of Nancy (France) University Hospital, who presented about the use of an AI-driven scoring system to measure histological disease activity in UC.
Dr. Peyrin-Biroulet, who is the president of ECCO and acts as the scientific secretary of the International Organization for the Study of IBD, added that the use of AI systems could mean that pathologists have more time to do other tasks. Not only that, but it’s also not always possible to have IBD pathologist in every center, everywhere in the world.
“If we can get something that will automatically evaluate the disease activity, I think it will be something fantastic,” Dr. Peyrin-Biroulet said, “and it’s the reason why we were thinking that there is a need for an automated method to measure histological activity in UC.”
Old concept enhancing current practice
The idea of using AI systems to aid diagnostics is not new but now makes even more sense in the post–COVID-19 era, suggested Aaron F. Pollett, MD, MSc, FRCPC, codirector of the division of diagnostic medical genetics at Mount Sinai Hospital in Toronto and a pathologist with a specialty interest in gastrointestinal pathology.
“When we talk about artificial intelligence and histology, there’s actually a very long history, it goes back over 30 years,” Dr. Pollett said, from assessing cervical samples to its use in breast screening.
What seems to be sudden flurry of activity in the world of AI and pathology in recent years comes down to having a higher capacity for looking at large images, having access to large data sets, and having a high amount of computing power, Dr. Pollet inferred. Moreover, “the capacity and the need for whole slide imaging has really grown especially in the last few years as the pandemic has forced centers to adopt.” The need to work remotely and flexibly across centers and the number of available pathologists have also played a role.
AI systems that use image-based retrieval systems are making good headway in IBD, particularly in the diagnosis of UC where “some of the initial research is showing it can be quite good,” said Dr. Pollett. The “patchiness that Crohn’s can have in comparison to UC” means that it’s still an emerging area, but can perhaps be useful for more questionable cases in which “having that degree of certainty can certainly help because there is a discrepancy between specialist and nonspecialist pathologists in the likelihood that what they predict on the biopsy will be the underlying disease.”
AI systems in IBD – do they work?
Histopathology is becoming increasingly integrated into IBD clinical trial design at the behest of the Food and Drug Administration and European associations such as ECCO. This can be a tedious procedure that can be prone to error and disagreement between scorers.
The AI-driven scoring system that Dr. Peyrin-Biroulet and associates have been working on aims to fix all that by using machine learning and image processing to set up a reproducible system. Their system, which is based on the Nancy histological index for UC, shows high correlation (87%) with histopathologists’ assessment and was 100% accurate in identifying images with high (grade 4) or no (grade 0) inflammatory activity. The accuracy decreased, however, when trying to distinguish between more moderate activity, with a 75% accuracy for identifying grade 3 and 82% accuracy for grades 1 or 2.
“I’m actually very fascinated to see how we can be supported by the AI work in our practice,” observed Francesca Rosini, a histopathologist working at S. Orsola–Malpighi University Hospital in Bologna, Italy.
Dr. Rosini, who chaired the digital oral presentation session in which Dr. Peyrin-Biroulet had presented also noted that “obviously for us as well [as AI systems] no activity or severe activity is the easiest part but when it’s in between that’s where the problems come.”
Simplifying histological scoring
Simplifying scoring for use in AI systems could be the key to their future success, as Tommaso Lorenzo Parigi, MD, from Humanitas University in Milan, and a research fellow at the University of Birmingham (England), suggested.
“Histology is particularly important to distinguish between mild activity and remission,” Dr. Parigi said. “More than 30 histological scores that have been proposed, but their adoption in clinical practice remains limited.”
Dr. Parigi has been part of an international team that has developed a simplified histological score based on “the presence of absence of neutrophils, regardless of their number,” since these are “key determinants of disease activity”.
The score, known as the Paddington International Virtual Chromoendoscopy Scre (PICaSSO) Histologic Remission Index (PHRI), has been shown to correlate well with endoscopic outcomes and thus a good measure to include in AI systems. The results of this work were published online in Gut to coincide with the ECCO congress.
“We are getting close to a world where we could screen biopsies with this kind of systems and consider skipping the pathologists result if AI detected activity,” Dr. Parigi provocatively suggested. “Of course, we need to increase and improve our sensitivity, and we are currently working on that to reduce false negatives, as well as training our model to use and apply other histological scores.”
Assessing the gut in real time
Perhaps one of the most exciting developments it to be able to use these AI technologies to examine the gut in real time.
“Virtual chromoendoscopy will give you the opportunity to distinguish very carefully all the details of mucosal vascular pattern,” said Marietta Iacucci MD, PhD, FASGE, AGAF, an associate professor and gastroenterology consultant at the Birmingham (England) University Hospitals.
“So AI can give you, in real time, the score but at the same time it can help to target, to do biopsies for healing,” Dr. Iacucci added when reporting the results of a study evaluating the performance of the first virtual chromoendoscopy AI system to detect endoscopic and histologic remission in UC.
The system was proven to predict endoscopic remission very accurately (94% using PICaSSO and 87% using the UC endoscopic index of severity) when compared with a human endoscopist. Rates of predicting histological remission were also high, at around 83%-85%, depending on the score used.
“For the future, this AI tool can expediate, support, and standardize the endoscopic evaluation of UC mucosal healing in clinical practice and in clinical trials,” Dr. Iacucci said.
The next steps are to combine virtual chromoendoscopy with the PHRI and to validate the tool in a multicenter, international PICaSSO-AI study.
The AI-driven scoring system presented by Dr. Peyrin-Biroulet was supported by Takeda. Dr. Peryin-Biroulet acknowledged the receipt of personal fees and grants from Takeda along with multiple other Pharma companies and owning stock options from CTMA. Dr. Iacucci has received research grants from Pentax, AbbVie, Olympus, and Fujifilm and personal fees from Pentax, AbbVie and Janssen. Dr. Pollett, Dr. Rosini, and Dr. Parigi had no financial conflicts of interest to disclose.
Not only are artificial intelligence (AI) systems potentially highly accurate for assessment of disease activity and remission of ulcerative colitis (UC), but they can mitigate some limits of human assessment, according to presentations at the 17th congress of the European Crohn’s and Colitis Organisation.
Importantly, AI systems have the potential to supplement the services of expert histopathologists and endoscopists rather than replace them, several experts asserted at the meeting.
“We will always need pathologists,” reassured inflammatory bowel disease (IBD) specialist Laurent Peyrin-Biroulet, MD, PhD, of Nancy (France) University Hospital, who presented about the use of an AI-driven scoring system to measure histological disease activity in UC.
Dr. Peyrin-Biroulet, who is the president of ECCO and acts as the scientific secretary of the International Organization for the Study of IBD, added that the use of AI systems could mean that pathologists have more time to do other tasks. Not only that, but it’s also not always possible to have IBD pathologist in every center, everywhere in the world.
“If we can get something that will automatically evaluate the disease activity, I think it will be something fantastic,” Dr. Peyrin-Biroulet said, “and it’s the reason why we were thinking that there is a need for an automated method to measure histological activity in UC.”
Old concept enhancing current practice
The idea of using AI systems to aid diagnostics is not new but now makes even more sense in the post–COVID-19 era, suggested Aaron F. Pollett, MD, MSc, FRCPC, codirector of the division of diagnostic medical genetics at Mount Sinai Hospital in Toronto and a pathologist with a specialty interest in gastrointestinal pathology.
“When we talk about artificial intelligence and histology, there’s actually a very long history, it goes back over 30 years,” Dr. Pollett said, from assessing cervical samples to its use in breast screening.
What seems to be sudden flurry of activity in the world of AI and pathology in recent years comes down to having a higher capacity for looking at large images, having access to large data sets, and having a high amount of computing power, Dr. Pollet inferred. Moreover, “the capacity and the need for whole slide imaging has really grown especially in the last few years as the pandemic has forced centers to adopt.” The need to work remotely and flexibly across centers and the number of available pathologists have also played a role.
AI systems that use image-based retrieval systems are making good headway in IBD, particularly in the diagnosis of UC where “some of the initial research is showing it can be quite good,” said Dr. Pollett. The “patchiness that Crohn’s can have in comparison to UC” means that it’s still an emerging area, but can perhaps be useful for more questionable cases in which “having that degree of certainty can certainly help because there is a discrepancy between specialist and nonspecialist pathologists in the likelihood that what they predict on the biopsy will be the underlying disease.”
AI systems in IBD – do they work?
Histopathology is becoming increasingly integrated into IBD clinical trial design at the behest of the Food and Drug Administration and European associations such as ECCO. This can be a tedious procedure that can be prone to error and disagreement between scorers.
The AI-driven scoring system that Dr. Peyrin-Biroulet and associates have been working on aims to fix all that by using machine learning and image processing to set up a reproducible system. Their system, which is based on the Nancy histological index for UC, shows high correlation (87%) with histopathologists’ assessment and was 100% accurate in identifying images with high (grade 4) or no (grade 0) inflammatory activity. The accuracy decreased, however, when trying to distinguish between more moderate activity, with a 75% accuracy for identifying grade 3 and 82% accuracy for grades 1 or 2.
“I’m actually very fascinated to see how we can be supported by the AI work in our practice,” observed Francesca Rosini, a histopathologist working at S. Orsola–Malpighi University Hospital in Bologna, Italy.
Dr. Rosini, who chaired the digital oral presentation session in which Dr. Peyrin-Biroulet had presented also noted that “obviously for us as well [as AI systems] no activity or severe activity is the easiest part but when it’s in between that’s where the problems come.”
Simplifying histological scoring
Simplifying scoring for use in AI systems could be the key to their future success, as Tommaso Lorenzo Parigi, MD, from Humanitas University in Milan, and a research fellow at the University of Birmingham (England), suggested.
“Histology is particularly important to distinguish between mild activity and remission,” Dr. Parigi said. “More than 30 histological scores that have been proposed, but their adoption in clinical practice remains limited.”
Dr. Parigi has been part of an international team that has developed a simplified histological score based on “the presence of absence of neutrophils, regardless of their number,” since these are “key determinants of disease activity”.
The score, known as the Paddington International Virtual Chromoendoscopy Scre (PICaSSO) Histologic Remission Index (PHRI), has been shown to correlate well with endoscopic outcomes and thus a good measure to include in AI systems. The results of this work were published online in Gut to coincide with the ECCO congress.
“We are getting close to a world where we could screen biopsies with this kind of systems and consider skipping the pathologists result if AI detected activity,” Dr. Parigi provocatively suggested. “Of course, we need to increase and improve our sensitivity, and we are currently working on that to reduce false negatives, as well as training our model to use and apply other histological scores.”
Assessing the gut in real time
Perhaps one of the most exciting developments it to be able to use these AI technologies to examine the gut in real time.
“Virtual chromoendoscopy will give you the opportunity to distinguish very carefully all the details of mucosal vascular pattern,” said Marietta Iacucci MD, PhD, FASGE, AGAF, an associate professor and gastroenterology consultant at the Birmingham (England) University Hospitals.
“So AI can give you, in real time, the score but at the same time it can help to target, to do biopsies for healing,” Dr. Iacucci added when reporting the results of a study evaluating the performance of the first virtual chromoendoscopy AI system to detect endoscopic and histologic remission in UC.
The system was proven to predict endoscopic remission very accurately (94% using PICaSSO and 87% using the UC endoscopic index of severity) when compared with a human endoscopist. Rates of predicting histological remission were also high, at around 83%-85%, depending on the score used.
“For the future, this AI tool can expediate, support, and standardize the endoscopic evaluation of UC mucosal healing in clinical practice and in clinical trials,” Dr. Iacucci said.
The next steps are to combine virtual chromoendoscopy with the PHRI and to validate the tool in a multicenter, international PICaSSO-AI study.
The AI-driven scoring system presented by Dr. Peyrin-Biroulet was supported by Takeda. Dr. Peryin-Biroulet acknowledged the receipt of personal fees and grants from Takeda along with multiple other Pharma companies and owning stock options from CTMA. Dr. Iacucci has received research grants from Pentax, AbbVie, Olympus, and Fujifilm and personal fees from Pentax, AbbVie and Janssen. Dr. Pollett, Dr. Rosini, and Dr. Parigi had no financial conflicts of interest to disclose.
FROM ECCO 2022
Endoscopic healing of Crohn’s disease could differ by biologic
Greater endoscopic healing at 1 year might be achieved in people with Crohn’s disease if they are treated with anti–tumor necrosis factor (TNF) drugs than if they are treated with certain other biologics it appears.
In a pooled analysis of data from four different clinical trial programs, which altogether included 344 patients with Crohn’s disease, both an infliximab biosimilar and adalimumab were associated with better endoscopic healing rates of both the ileum and colon than were either vedolizumab or ustekinumab.
The difference disappeared for ileal not colonic involvement, however, if patients had been biologic naive before receiving any of the four drugs that were compared.
“Recent studies have suggested that the ileum and colon differ with regards to their ability to achieve healing in Crohn’s disease,” Neeraj Narula, MD, said in reporting the analysis at the 17th congress of the European Crohn’s and Colitis Organisation.
“Our group has shown that larger ulcers in the ileum and rectum in particular do not heal as well as other areas of the colon when using infliximab therapies,” added Dr. Narula, who is an assistant professor of medicine at McMaster University, Hamilton, Ont., and the director of the IBD clinic and staff gastroenterologist at Hamilton Health Sciences.
Whether there are differences in how the ileal and colonic regions heal in response to biologic therapy is not known, which is why Dr. Narula and colleagues carried out their analysis.
Pooling pivotal trial program data
“Our primary aim was to evaluate the efficacy of four approved biologic therapies for Crohn’s disease with regards to their ability to achieve endoscopic healing after continuous use for 1 year,” he noted.
For their analysis, original data from the EXTEND, UNITI, VERSIFY, and infliximab biosimilar CT-P13 clinical trial programs were obtained and pooled.
The extent of mucosal inflammation and thereby healing were determined using a modified version of the Simple Endoscopic Score for Crohn’s disease (SES-CD), which is a measure often used in clinical trials.
At inclusion, patients had to have had an SES-CD score of 3 or more in at least one segment of the ileum or colon and confirmed ulceration. The primary endpoint was endoscopic healing defined as an SES-CD score of 0 after 1 year’s continuous treatment.
Multivariate logistic regression was used, and adjustments were made for potential confounding factors, such as how long people had had Crohn’s disease, the use of steroids, and if there had been prior anti-TNF failure.
Main results
Overall, 299 patients were in the final analysis; most (n = 141) had been treated with the infliximab biosimilar, with 61 treated with adalimumab, 56 vedolizumab, and 41 ustekinumab.
The highest rate of endoscopic healing at 1 year for ileal involvement was seen with the infliximab biosimilar (36.7% of patients) and the lowest rate with vedolizumab (18.6%), with rates of 30% and 22.7% for adalimumab and ustekinumab, respectively. Only the comparison between the infliximab biosimilar and vedolizumab was statistically significant (P = .038).
As for ileal ulcers, there were fewer seen with both anti-TNF treatments than with either ustekinumab or vedolizumab, at 40.8% for the infliximab biosimilar, 30% for adalimumab, 17.7% for ustekinumab, and 8.7% for vedolizumab. Rates of ileal ulcer absence in biologic-naive patients were a respective 36.7%, 37.5%, 40%, and 21.9%.
In terms of colonic involvement, the lowest rate of endoscopic healing occurred in patients treated with ustekinumab, at 29%, and the highest for adalimumab (62.5%), followed by the infliximab biosimilar (52.4%) and then vedolizumab (31.3%).
Absence of colonic ulcers was similarly low for ustekinumab (29.6%) and higher for the other three groups (64.9%, 70.5%, and 41.2%, respectively). When considering biologic-naive patients, there was a significant difference in the absence of colonic ulcers comparing adalimumab (66.7; P = .004) and the infliximab biosimilar (52.4%; P = .022), but not vedolizumab (37.1%) versus ustekinumab (29.4%).
Lots of questions and limitations
Dr. Narula’s presentation garnered a lot of questions, with viewers noting that the number of patients was too small or methodologically too flawed to be able to draw any sound conclusions.
“We acknowledge that our study cannot substitute for head-to-head trials of biologics in Crohn’s disease since we cannot account for all confounding variables,” said Dr. Narula.
“We did try to account for this limitation by performing some subgroup analyses to account for biologic-naive patients only,” he added, alongside the multivariate analyses.
Also, there might be a difference in the duration of treatment needed before endoscopic healing is seen, as the biologics studied all have a different duration of onset. The dosages used may also be important, and Dr. Narula conceded that their analyses were done assuming standard doses, which may not have been optimized.
There were several demographic differences between the infliximab arm and the other treatments. Of note, 76% of patients had been given immunomodulators at the same time, which is known to enhance the effects of infliximab.
Dr. Narula pointed out, however, that baseline characteristic were pretty similar in the other three study arms, and adalimumab still showed superiority in the analyses that were performed.
So are anti-TNFs the best choice?
“Ultimately, we always factor in the therapeutic index of therapy, trying to weigh benefit versus risk,” Dr. Narula said in answering a question from the chair of the session on the risks associated with anti-TNFs.
“We didn’t compare risk within this clinical trial, but certainly risk can be compared, and there’s things like number needed to treat versus number needed to harm to ultimately come at a best answer for the patient,” he added.
Dr. Narula disclosed receiving grants from Takeda and Pfizer; personal fees from AbbVie, Janssen, Takeda, Pfizer, Merck, Amgen, and Sandoz; and nonfinancial support from AbbVie, Janssen, Takeda, Pfizer, Ferring, and Lupin. The data used in the analysis were obtained through YODA Project #2021-4778 which has an agreement with Janssen Research & Developmen and via Vivli, which has access to data from AbbVie and Takeda. Data were also obtained with permission from Celltrion.
Greater endoscopic healing at 1 year might be achieved in people with Crohn’s disease if they are treated with anti–tumor necrosis factor (TNF) drugs than if they are treated with certain other biologics it appears.
In a pooled analysis of data from four different clinical trial programs, which altogether included 344 patients with Crohn’s disease, both an infliximab biosimilar and adalimumab were associated with better endoscopic healing rates of both the ileum and colon than were either vedolizumab or ustekinumab.
The difference disappeared for ileal not colonic involvement, however, if patients had been biologic naive before receiving any of the four drugs that were compared.
“Recent studies have suggested that the ileum and colon differ with regards to their ability to achieve healing in Crohn’s disease,” Neeraj Narula, MD, said in reporting the analysis at the 17th congress of the European Crohn’s and Colitis Organisation.
“Our group has shown that larger ulcers in the ileum and rectum in particular do not heal as well as other areas of the colon when using infliximab therapies,” added Dr. Narula, who is an assistant professor of medicine at McMaster University, Hamilton, Ont., and the director of the IBD clinic and staff gastroenterologist at Hamilton Health Sciences.
Whether there are differences in how the ileal and colonic regions heal in response to biologic therapy is not known, which is why Dr. Narula and colleagues carried out their analysis.
Pooling pivotal trial program data
“Our primary aim was to evaluate the efficacy of four approved biologic therapies for Crohn’s disease with regards to their ability to achieve endoscopic healing after continuous use for 1 year,” he noted.
For their analysis, original data from the EXTEND, UNITI, VERSIFY, and infliximab biosimilar CT-P13 clinical trial programs were obtained and pooled.
The extent of mucosal inflammation and thereby healing were determined using a modified version of the Simple Endoscopic Score for Crohn’s disease (SES-CD), which is a measure often used in clinical trials.
At inclusion, patients had to have had an SES-CD score of 3 or more in at least one segment of the ileum or colon and confirmed ulceration. The primary endpoint was endoscopic healing defined as an SES-CD score of 0 after 1 year’s continuous treatment.
Multivariate logistic regression was used, and adjustments were made for potential confounding factors, such as how long people had had Crohn’s disease, the use of steroids, and if there had been prior anti-TNF failure.
Main results
Overall, 299 patients were in the final analysis; most (n = 141) had been treated with the infliximab biosimilar, with 61 treated with adalimumab, 56 vedolizumab, and 41 ustekinumab.
The highest rate of endoscopic healing at 1 year for ileal involvement was seen with the infliximab biosimilar (36.7% of patients) and the lowest rate with vedolizumab (18.6%), with rates of 30% and 22.7% for adalimumab and ustekinumab, respectively. Only the comparison between the infliximab biosimilar and vedolizumab was statistically significant (P = .038).
As for ileal ulcers, there were fewer seen with both anti-TNF treatments than with either ustekinumab or vedolizumab, at 40.8% for the infliximab biosimilar, 30% for adalimumab, 17.7% for ustekinumab, and 8.7% for vedolizumab. Rates of ileal ulcer absence in biologic-naive patients were a respective 36.7%, 37.5%, 40%, and 21.9%.
In terms of colonic involvement, the lowest rate of endoscopic healing occurred in patients treated with ustekinumab, at 29%, and the highest for adalimumab (62.5%), followed by the infliximab biosimilar (52.4%) and then vedolizumab (31.3%).
Absence of colonic ulcers was similarly low for ustekinumab (29.6%) and higher for the other three groups (64.9%, 70.5%, and 41.2%, respectively). When considering biologic-naive patients, there was a significant difference in the absence of colonic ulcers comparing adalimumab (66.7; P = .004) and the infliximab biosimilar (52.4%; P = .022), but not vedolizumab (37.1%) versus ustekinumab (29.4%).
Lots of questions and limitations
Dr. Narula’s presentation garnered a lot of questions, with viewers noting that the number of patients was too small or methodologically too flawed to be able to draw any sound conclusions.
“We acknowledge that our study cannot substitute for head-to-head trials of biologics in Crohn’s disease since we cannot account for all confounding variables,” said Dr. Narula.
“We did try to account for this limitation by performing some subgroup analyses to account for biologic-naive patients only,” he added, alongside the multivariate analyses.
Also, there might be a difference in the duration of treatment needed before endoscopic healing is seen, as the biologics studied all have a different duration of onset. The dosages used may also be important, and Dr. Narula conceded that their analyses were done assuming standard doses, which may not have been optimized.
There were several demographic differences between the infliximab arm and the other treatments. Of note, 76% of patients had been given immunomodulators at the same time, which is known to enhance the effects of infliximab.
Dr. Narula pointed out, however, that baseline characteristic were pretty similar in the other three study arms, and adalimumab still showed superiority in the analyses that were performed.
So are anti-TNFs the best choice?
“Ultimately, we always factor in the therapeutic index of therapy, trying to weigh benefit versus risk,” Dr. Narula said in answering a question from the chair of the session on the risks associated with anti-TNFs.
“We didn’t compare risk within this clinical trial, but certainly risk can be compared, and there’s things like number needed to treat versus number needed to harm to ultimately come at a best answer for the patient,” he added.
Dr. Narula disclosed receiving grants from Takeda and Pfizer; personal fees from AbbVie, Janssen, Takeda, Pfizer, Merck, Amgen, and Sandoz; and nonfinancial support from AbbVie, Janssen, Takeda, Pfizer, Ferring, and Lupin. The data used in the analysis were obtained through YODA Project #2021-4778 which has an agreement with Janssen Research & Developmen and via Vivli, which has access to data from AbbVie and Takeda. Data were also obtained with permission from Celltrion.
Greater endoscopic healing at 1 year might be achieved in people with Crohn’s disease if they are treated with anti–tumor necrosis factor (TNF) drugs than if they are treated with certain other biologics it appears.
In a pooled analysis of data from four different clinical trial programs, which altogether included 344 patients with Crohn’s disease, both an infliximab biosimilar and adalimumab were associated with better endoscopic healing rates of both the ileum and colon than were either vedolizumab or ustekinumab.
The difference disappeared for ileal not colonic involvement, however, if patients had been biologic naive before receiving any of the four drugs that were compared.
“Recent studies have suggested that the ileum and colon differ with regards to their ability to achieve healing in Crohn’s disease,” Neeraj Narula, MD, said in reporting the analysis at the 17th congress of the European Crohn’s and Colitis Organisation.
“Our group has shown that larger ulcers in the ileum and rectum in particular do not heal as well as other areas of the colon when using infliximab therapies,” added Dr. Narula, who is an assistant professor of medicine at McMaster University, Hamilton, Ont., and the director of the IBD clinic and staff gastroenterologist at Hamilton Health Sciences.
Whether there are differences in how the ileal and colonic regions heal in response to biologic therapy is not known, which is why Dr. Narula and colleagues carried out their analysis.
Pooling pivotal trial program data
“Our primary aim was to evaluate the efficacy of four approved biologic therapies for Crohn’s disease with regards to their ability to achieve endoscopic healing after continuous use for 1 year,” he noted.
For their analysis, original data from the EXTEND, UNITI, VERSIFY, and infliximab biosimilar CT-P13 clinical trial programs were obtained and pooled.
The extent of mucosal inflammation and thereby healing were determined using a modified version of the Simple Endoscopic Score for Crohn’s disease (SES-CD), which is a measure often used in clinical trials.
At inclusion, patients had to have had an SES-CD score of 3 or more in at least one segment of the ileum or colon and confirmed ulceration. The primary endpoint was endoscopic healing defined as an SES-CD score of 0 after 1 year’s continuous treatment.
Multivariate logistic regression was used, and adjustments were made for potential confounding factors, such as how long people had had Crohn’s disease, the use of steroids, and if there had been prior anti-TNF failure.
Main results
Overall, 299 patients were in the final analysis; most (n = 141) had been treated with the infliximab biosimilar, with 61 treated with adalimumab, 56 vedolizumab, and 41 ustekinumab.
The highest rate of endoscopic healing at 1 year for ileal involvement was seen with the infliximab biosimilar (36.7% of patients) and the lowest rate with vedolizumab (18.6%), with rates of 30% and 22.7% for adalimumab and ustekinumab, respectively. Only the comparison between the infliximab biosimilar and vedolizumab was statistically significant (P = .038).
As for ileal ulcers, there were fewer seen with both anti-TNF treatments than with either ustekinumab or vedolizumab, at 40.8% for the infliximab biosimilar, 30% for adalimumab, 17.7% for ustekinumab, and 8.7% for vedolizumab. Rates of ileal ulcer absence in biologic-naive patients were a respective 36.7%, 37.5%, 40%, and 21.9%.
In terms of colonic involvement, the lowest rate of endoscopic healing occurred in patients treated with ustekinumab, at 29%, and the highest for adalimumab (62.5%), followed by the infliximab biosimilar (52.4%) and then vedolizumab (31.3%).
Absence of colonic ulcers was similarly low for ustekinumab (29.6%) and higher for the other three groups (64.9%, 70.5%, and 41.2%, respectively). When considering biologic-naive patients, there was a significant difference in the absence of colonic ulcers comparing adalimumab (66.7; P = .004) and the infliximab biosimilar (52.4%; P = .022), but not vedolizumab (37.1%) versus ustekinumab (29.4%).
Lots of questions and limitations
Dr. Narula’s presentation garnered a lot of questions, with viewers noting that the number of patients was too small or methodologically too flawed to be able to draw any sound conclusions.
“We acknowledge that our study cannot substitute for head-to-head trials of biologics in Crohn’s disease since we cannot account for all confounding variables,” said Dr. Narula.
“We did try to account for this limitation by performing some subgroup analyses to account for biologic-naive patients only,” he added, alongside the multivariate analyses.
Also, there might be a difference in the duration of treatment needed before endoscopic healing is seen, as the biologics studied all have a different duration of onset. The dosages used may also be important, and Dr. Narula conceded that their analyses were done assuming standard doses, which may not have been optimized.
There were several demographic differences between the infliximab arm and the other treatments. Of note, 76% of patients had been given immunomodulators at the same time, which is known to enhance the effects of infliximab.
Dr. Narula pointed out, however, that baseline characteristic were pretty similar in the other three study arms, and adalimumab still showed superiority in the analyses that were performed.
So are anti-TNFs the best choice?
“Ultimately, we always factor in the therapeutic index of therapy, trying to weigh benefit versus risk,” Dr. Narula said in answering a question from the chair of the session on the risks associated with anti-TNFs.
“We didn’t compare risk within this clinical trial, but certainly risk can be compared, and there’s things like number needed to treat versus number needed to harm to ultimately come at a best answer for the patient,” he added.
Dr. Narula disclosed receiving grants from Takeda and Pfizer; personal fees from AbbVie, Janssen, Takeda, Pfizer, Merck, Amgen, and Sandoz; and nonfinancial support from AbbVie, Janssen, Takeda, Pfizer, Ferring, and Lupin. The data used in the analysis were obtained through YODA Project #2021-4778 which has an agreement with Janssen Research & Developmen and via Vivli, which has access to data from AbbVie and Takeda. Data were also obtained with permission from Celltrion.
FROM ECCO 2022
IBD-VTE score serves as reminder to assess postdischarge risk
The chances of developing a blood clot after hospital admission for inflammatory bowel disease (IBD) may persist for several months after being discharged, but a new simple score might help clinicians identify patients who are at greatest risk.
The score – which takes eight, easily captured factors into consideration – had a reasonable ability to distinguish between people who did and did not develop venous thromboembolism (VTE), with an area under the curve of 0.71 (95% confidence interval, 0.69-0.72).
“There is clearly an excess of risk for VTE in patients admitted for IBD in the 90 days following their hospital discharge,” said Philip Harvey, MD, a consultant gastroenterologist with the Royal Wolverhampton (England) NHS Trust at the 17th congress of the European Crohn’s and Colitis Organisation.
“Advancing age, male gender, emergency admission, longer admissions, and ulcerative colitis are particularly important risk factors,” he noted.
“We have proposed a risk-scoring system that will be generalizable to patients under the age of 60 using readily identifiable clinical data so that clinicians can identify patients who are at the greatest risk,” Dr. Harvey added when presenting the work.
“This research provides much needed evidence to guide posthospitalization anticoagulation in patients hospitalized for IBD flares,” Bharati Kochar, MD, MS, independently commented.
“Surgeons are already discharging select patients on anticoagulation for DVT [deep vein thrombosis] prophylaxis [but] we need to consider this more systematically after medical IBD admissions,” suggested Dr. Kochar, who is a gastroenterologist and IBD specialist at Massachusetts General Hospital in Boston.
“This research should spur prospective investigation into type of anticoagulation upon discharge, dose, duration and whether the intervention makes a difference in postdischarge clotting events in patients hospitalized for a flare of IBD,” she added.
VTE risk in IBD patients
The risk and prevention of VTE and arterial thrombosis in IBD patients was the focus of a recent international consensus project in which 14 international IBD experts and three thrombosis experts from 12 countries came together to develop evidence-based guidance. Nineteen statements and 10 core recommendations were made, notably that “patients with IBD should be screened for VTE risk factors” and that “thromboprophylaxis should be given to patients with IBD during hospitalization of any cause and maintained during the inpatient period.”
Although met with a high level of agreement among the expert panel, these recommendations were supported by a low (grade C/D) level of evidence.
The expert panel observed in their conclusions that “development of specific risk-assessment tools for thrombotic complications in patients with IBD are needed, as they might influence management in some clinical scenarios (such as thromboprophylaxis during ambulatory flares).”
Large hospitalized IBD population considered
Dr. Harvey and fellow investigators’ IBD-VTE risk score was created using data from almost 102,000 patients (49,385 of whom were men) with just greater than 201,000 hospital admissions between 2006 and 2019. These data were taken from the Hospital Episode Statistics (HES), a “data warehouse” that collects details of all emergency, routine, and outpatient hospital attendances at NHS hospitals in England.
“The HES database is advantageous due to its size because VTE events are relatively uncommon in this group, and therefore it’s important to capture as many patients as possible,” Dr. Harvey explained.
All admissions, from emergencies without surgery to those involving surgery, and those for more routine cases of elective surgery were considered, with the most common (79.3%) admission type being nonsurgical emergencies.
A multilevel logistic regression model was used to identify patient and admission factors that might influence the risk for VTE.
With regard to the number of VTE events seen, Dr. Harvey noted: “There was an enormous excess of events and risk in that 0-90 day period, compared to 180-270 days later. This was true across all admission types.”
Indeed, VTE rates per 100,000 people in the 0-90 day postoperative period were 36.9 for emergency surgical admissions, and 15.6 for both nonsurgical emergencies and elective surgeries. Rates in the later period were a respective 0.84, 1.59, and 1.70.
Key risk factors for VTE were male gender, older age, emergency admission with or without surgery, longer hospital stays, and having ulcerative colitis which were included in the scoring system together with number of prior IBD hospital admissions in the past 3 months, ethnicity, and number of comorbidities.
Ideal thromboprophylaxis duration under investigation
“A higher risk of DVT is known in these patients and all should be considered for postoperative VTE prevention,” said Robert Neil Goldstone, MD, who is assistant professor of surgery at Massachusetts General Hospital.
“Many scores can be used, including the Caprini score, which also adds a point for patient history of IBD,” he observed.
The flip-side of VTE is of course the risk for postsurgical bleeding. While this is something clinicians need to be cognizant of there is “not generally increased risk” with some of the more commonly used anticoagulants, Dr. Goldstone noted. In his practice, “high-risk” IBD patients who have undergone bowel surgery will commonly be discharged on a low-molecular-weight heparin treatment for at least 3-4 weeks.
“The bigger question that remains is whether prolonged postoperative thromboprophylaxis is required,” Dr. Goldstone said. This is something that needs examining in a large randomized controlled trial.
Dr. Harvey and coinvestigators had no conflicts of interest to disclose. Dr. Kochar is on the Board of Editors for GI & Hepatology News but had no other conflicts of interest. Dr. Goldstone was also not involved in the study and had nothing to disclose.
The chances of developing a blood clot after hospital admission for inflammatory bowel disease (IBD) may persist for several months after being discharged, but a new simple score might help clinicians identify patients who are at greatest risk.
The score – which takes eight, easily captured factors into consideration – had a reasonable ability to distinguish between people who did and did not develop venous thromboembolism (VTE), with an area under the curve of 0.71 (95% confidence interval, 0.69-0.72).
“There is clearly an excess of risk for VTE in patients admitted for IBD in the 90 days following their hospital discharge,” said Philip Harvey, MD, a consultant gastroenterologist with the Royal Wolverhampton (England) NHS Trust at the 17th congress of the European Crohn’s and Colitis Organisation.
“Advancing age, male gender, emergency admission, longer admissions, and ulcerative colitis are particularly important risk factors,” he noted.
“We have proposed a risk-scoring system that will be generalizable to patients under the age of 60 using readily identifiable clinical data so that clinicians can identify patients who are at the greatest risk,” Dr. Harvey added when presenting the work.
“This research provides much needed evidence to guide posthospitalization anticoagulation in patients hospitalized for IBD flares,” Bharati Kochar, MD, MS, independently commented.
“Surgeons are already discharging select patients on anticoagulation for DVT [deep vein thrombosis] prophylaxis [but] we need to consider this more systematically after medical IBD admissions,” suggested Dr. Kochar, who is a gastroenterologist and IBD specialist at Massachusetts General Hospital in Boston.
“This research should spur prospective investigation into type of anticoagulation upon discharge, dose, duration and whether the intervention makes a difference in postdischarge clotting events in patients hospitalized for a flare of IBD,” she added.
VTE risk in IBD patients
The risk and prevention of VTE and arterial thrombosis in IBD patients was the focus of a recent international consensus project in which 14 international IBD experts and three thrombosis experts from 12 countries came together to develop evidence-based guidance. Nineteen statements and 10 core recommendations were made, notably that “patients with IBD should be screened for VTE risk factors” and that “thromboprophylaxis should be given to patients with IBD during hospitalization of any cause and maintained during the inpatient period.”
Although met with a high level of agreement among the expert panel, these recommendations were supported by a low (grade C/D) level of evidence.
The expert panel observed in their conclusions that “development of specific risk-assessment tools for thrombotic complications in patients with IBD are needed, as they might influence management in some clinical scenarios (such as thromboprophylaxis during ambulatory flares).”
Large hospitalized IBD population considered
Dr. Harvey and fellow investigators’ IBD-VTE risk score was created using data from almost 102,000 patients (49,385 of whom were men) with just greater than 201,000 hospital admissions between 2006 and 2019. These data were taken from the Hospital Episode Statistics (HES), a “data warehouse” that collects details of all emergency, routine, and outpatient hospital attendances at NHS hospitals in England.
“The HES database is advantageous due to its size because VTE events are relatively uncommon in this group, and therefore it’s important to capture as many patients as possible,” Dr. Harvey explained.
All admissions, from emergencies without surgery to those involving surgery, and those for more routine cases of elective surgery were considered, with the most common (79.3%) admission type being nonsurgical emergencies.
A multilevel logistic regression model was used to identify patient and admission factors that might influence the risk for VTE.
With regard to the number of VTE events seen, Dr. Harvey noted: “There was an enormous excess of events and risk in that 0-90 day period, compared to 180-270 days later. This was true across all admission types.”
Indeed, VTE rates per 100,000 people in the 0-90 day postoperative period were 36.9 for emergency surgical admissions, and 15.6 for both nonsurgical emergencies and elective surgeries. Rates in the later period were a respective 0.84, 1.59, and 1.70.
Key risk factors for VTE were male gender, older age, emergency admission with or without surgery, longer hospital stays, and having ulcerative colitis which were included in the scoring system together with number of prior IBD hospital admissions in the past 3 months, ethnicity, and number of comorbidities.
Ideal thromboprophylaxis duration under investigation
“A higher risk of DVT is known in these patients and all should be considered for postoperative VTE prevention,” said Robert Neil Goldstone, MD, who is assistant professor of surgery at Massachusetts General Hospital.
“Many scores can be used, including the Caprini score, which also adds a point for patient history of IBD,” he observed.
The flip-side of VTE is of course the risk for postsurgical bleeding. While this is something clinicians need to be cognizant of there is “not generally increased risk” with some of the more commonly used anticoagulants, Dr. Goldstone noted. In his practice, “high-risk” IBD patients who have undergone bowel surgery will commonly be discharged on a low-molecular-weight heparin treatment for at least 3-4 weeks.
“The bigger question that remains is whether prolonged postoperative thromboprophylaxis is required,” Dr. Goldstone said. This is something that needs examining in a large randomized controlled trial.
Dr. Harvey and coinvestigators had no conflicts of interest to disclose. Dr. Kochar is on the Board of Editors for GI & Hepatology News but had no other conflicts of interest. Dr. Goldstone was also not involved in the study and had nothing to disclose.
The chances of developing a blood clot after hospital admission for inflammatory bowel disease (IBD) may persist for several months after being discharged, but a new simple score might help clinicians identify patients who are at greatest risk.
The score – which takes eight, easily captured factors into consideration – had a reasonable ability to distinguish between people who did and did not develop venous thromboembolism (VTE), with an area under the curve of 0.71 (95% confidence interval, 0.69-0.72).
“There is clearly an excess of risk for VTE in patients admitted for IBD in the 90 days following their hospital discharge,” said Philip Harvey, MD, a consultant gastroenterologist with the Royal Wolverhampton (England) NHS Trust at the 17th congress of the European Crohn’s and Colitis Organisation.
“Advancing age, male gender, emergency admission, longer admissions, and ulcerative colitis are particularly important risk factors,” he noted.
“We have proposed a risk-scoring system that will be generalizable to patients under the age of 60 using readily identifiable clinical data so that clinicians can identify patients who are at the greatest risk,” Dr. Harvey added when presenting the work.
“This research provides much needed evidence to guide posthospitalization anticoagulation in patients hospitalized for IBD flares,” Bharati Kochar, MD, MS, independently commented.
“Surgeons are already discharging select patients on anticoagulation for DVT [deep vein thrombosis] prophylaxis [but] we need to consider this more systematically after medical IBD admissions,” suggested Dr. Kochar, who is a gastroenterologist and IBD specialist at Massachusetts General Hospital in Boston.
“This research should spur prospective investigation into type of anticoagulation upon discharge, dose, duration and whether the intervention makes a difference in postdischarge clotting events in patients hospitalized for a flare of IBD,” she added.
VTE risk in IBD patients
The risk and prevention of VTE and arterial thrombosis in IBD patients was the focus of a recent international consensus project in which 14 international IBD experts and three thrombosis experts from 12 countries came together to develop evidence-based guidance. Nineteen statements and 10 core recommendations were made, notably that “patients with IBD should be screened for VTE risk factors” and that “thromboprophylaxis should be given to patients with IBD during hospitalization of any cause and maintained during the inpatient period.”
Although met with a high level of agreement among the expert panel, these recommendations were supported by a low (grade C/D) level of evidence.
The expert panel observed in their conclusions that “development of specific risk-assessment tools for thrombotic complications in patients with IBD are needed, as they might influence management in some clinical scenarios (such as thromboprophylaxis during ambulatory flares).”
Large hospitalized IBD population considered
Dr. Harvey and fellow investigators’ IBD-VTE risk score was created using data from almost 102,000 patients (49,385 of whom were men) with just greater than 201,000 hospital admissions between 2006 and 2019. These data were taken from the Hospital Episode Statistics (HES), a “data warehouse” that collects details of all emergency, routine, and outpatient hospital attendances at NHS hospitals in England.
“The HES database is advantageous due to its size because VTE events are relatively uncommon in this group, and therefore it’s important to capture as many patients as possible,” Dr. Harvey explained.
All admissions, from emergencies without surgery to those involving surgery, and those for more routine cases of elective surgery were considered, with the most common (79.3%) admission type being nonsurgical emergencies.
A multilevel logistic regression model was used to identify patient and admission factors that might influence the risk for VTE.
With regard to the number of VTE events seen, Dr. Harvey noted: “There was an enormous excess of events and risk in that 0-90 day period, compared to 180-270 days later. This was true across all admission types.”
Indeed, VTE rates per 100,000 people in the 0-90 day postoperative period were 36.9 for emergency surgical admissions, and 15.6 for both nonsurgical emergencies and elective surgeries. Rates in the later period were a respective 0.84, 1.59, and 1.70.
Key risk factors for VTE were male gender, older age, emergency admission with or without surgery, longer hospital stays, and having ulcerative colitis which were included in the scoring system together with number of prior IBD hospital admissions in the past 3 months, ethnicity, and number of comorbidities.
Ideal thromboprophylaxis duration under investigation
“A higher risk of DVT is known in these patients and all should be considered for postoperative VTE prevention,” said Robert Neil Goldstone, MD, who is assistant professor of surgery at Massachusetts General Hospital.
“Many scores can be used, including the Caprini score, which also adds a point for patient history of IBD,” he observed.
The flip-side of VTE is of course the risk for postsurgical bleeding. While this is something clinicians need to be cognizant of there is “not generally increased risk” with some of the more commonly used anticoagulants, Dr. Goldstone noted. In his practice, “high-risk” IBD patients who have undergone bowel surgery will commonly be discharged on a low-molecular-weight heparin treatment for at least 3-4 weeks.
“The bigger question that remains is whether prolonged postoperative thromboprophylaxis is required,” Dr. Goldstone said. This is something that needs examining in a large randomized controlled trial.
Dr. Harvey and coinvestigators had no conflicts of interest to disclose. Dr. Kochar is on the Board of Editors for GI & Hepatology News but had no other conflicts of interest. Dr. Goldstone was also not involved in the study and had nothing to disclose.
FROM ECCO 2022
LUCENT-1: Mirikizumab sees phase 3 success in UC treatment
Mirikizumab is the first interleukin (IL) 23p19 to report positive phase 3 results for induction therapy in patients who have moderate to severe ulcerative colitis (UC) and have already been treated with at least one prior therapy.
Compared to placebo, almost a quarter (24.2%) of patients treated with mirikizumab versus 13% of those treated with placebo were in clinical remission at the end of the 12-week LUCENT-1 study. This was the study’s primary endpoint and it was a significant result (P = .00006), study investigator Geert D’Haens, MD, PhD, reported at the 17th congress of the European Crohn’s and Colitis Organisation.
Moreover, mirikizumab met all its secondary endpoints in the trial. At the end of the study almost two-thirds (63.5%) of patients achieved a clinical response (vs. 42.2% in the placebo arm); over one-third (36.3%) exhibited endoscopic remission (vs. 21.1%), and just over a quarter (27.1% vs. 13.9%) showed histologic-endoscopic mucosal improvement, according to a press release. The P values for all comparisons were less than .00001.
Perhaps more importantly from the patient perspective, there was greater symptomatic improvement and less bowel urgency in those treated with mirikizumab versus those randomized to placebo.
“The results confirmed [the] efficacy and safety noted in the phase 2 induction [trials], and supports mirikizumab’s potential as treatment for ulcerative colitis,” said Dr. D’Haens, professor of gastroenterology and hepatology at Amsterdam University Medical Centers.
Dominik Bettenworth, MD, who was not involved in the study, said that “the positive results from the LUCENT-1 trial are an important step towards selective IL-23 inhibition as a new mode of action for the treatment of patients with UC.
“This treatment approach has been shown efficacious and launched in other immune-mediated diseases such as psoriasis,” said Dr. Bettenworth, a specialist in internal medicine and gastroenterology in Münster, Germany.
“Noteworthy, for the first time in a phase 3 trial in IBD, [bowel] urgency has been assessed as a secondary endpoint – a clinical symptom of particular importance for patients with UC,” he added, noting that regarding safety, “the LUCENT-1 trial further confirms the previously observed overall good safety profile of IL-23 inhibitors.”
About mirikizumab and LUCENT-1
Mirikizumab is a humanized monoclonal antibody directed against the p19 subunit of IL-23 and is one of several IL23p19 antibodies currently under investigation for the treatment of IBD.
LUCENT-1 was a multicenter, randomized, double-blind, parallel group, placebo-controlled induction study in just over 1,200 patients aged 18-80 years. For inclusion, patients had to have moderately to severely active UC and had to have received at least one prior therapy, but had an inadequate or loss of response to it or been intolerant of it. Baseline data showed that 40% of patients included had been treated with corticosteroids and 24% with immunomodulators, and any current treatment remained unchanged during the study. Biologic treatment had failed in about 40% of patients and any patient taking such therapy had to discontinue it before participating in the trial.
Patients were randomized to receive 300 mg of mirikizumab or matching placebo, given intravenously at weeks 0, 4, and 8. Dr. D’Haens noted that randomization had been in a 3:1 ratio and had been stratified according to various factors such as biologic failure status, corticosteroid use, baseline disease activity, and region of the world where the patient was recruited.
Better results if biologic naive
Clinical remission was stringently defined as: Mayo stool frequency subscore of zero or one, with a reduction of one point or greater from baseline; no rectal bleeding; and a Mayo endoscopic subscore of zero to one. When looking at this primary endpoint in terms of whether patients had received prior biologic treatment, there was a higher remission rate at week 12 if patients had not previously been given any biologic therapy than if they had, but rates were still higher than placebo (30.9% vs. 15.8% and 15.2% vs. 8.5%, respectively), according to the press release. The P value was less than .001 for both comparisons although the study was not powered to look at these subgroups of patients.
Similarly, for clinical response – which was a decrease in the modified Mayo score of 2 or more points and at least a 30% decrease from initial values, as well as a decrease in rectal bleeding – there were differences between patients who had (54.6% for mirikizumab vs. 29.7% for placebo) and had not (70.1% vs. 50.3%) received a biologic previously (again, P less than .001 for both comparisons).
“Control of bowel function is one of the most debilitating, or one of the most important features for patients with ulcerative colitis,” Dr. D’Haens said when presenting the data on bowel urgency. In the trial there was an improvement in urgency – which was rated by patients – starting as early as week 2, with further improvement seen as the induction period went on.
Mirikizumab safety consistent with other trials
Dr. D’Haens noted that the safety profile of IL23 antibodies was “extremely clean.” As with other trials of mirikizumab, he said, there were similar or lower rates to placebo for many adverse events including any infection (15.1% vs. 14%) and cerebrocardiovascular events (0.6% vs. 0.1%). The overall rate of treatment emergent adverse events was 44.5% vs. 46.1% for mirikizumab and placebo. Notably, there were fewer serious adverse events (2.8% vs. 5.3%.) and discontinuations because of side effects (1.6% vs. 7.2%) in the mirikizumab group.
Are gastroenterologists now spoiled for choice?
Lots of questions followed Dr. D’Haens presentation, many picking up on the high placebo response and remission rates.
“We’ve seen it in a number of trials now,” Dr. D’Haens said. “One of the reasons is that patients are allowed to start corticosteroids as late as 2 weeks before randomization,” he observed. In LUCENT-1, half of the patients that were using steroids were receiving a dose of 20 mg of prednisone.
“Now when you start 20 mg of prednisone 2 weeks before randomization that might have an impact on your placebo readout. So I think that’s a lesson for many more trials in the future,” Dr. D’Haens said,”
A high placebo response rate was not expected and another hypothesis is that maybe additional clinical support for fatigue that was received may have played a role.
Several delegates asked for guidance on where mirikizumab and other IL-23p19 blockers might now fit in the grand scheme of patient treatment.
“It is really nice to have expanding therapeutic options but how will we choose?” said one in the online Q&A. “Which IL23 antagonist should we be using now?” and “Is ustekinumab obsolete in UC?” asked others.
“I think it’s early days to decide where the field is going,” Dr. D’Haens said after his presentation. “We don’t have head-to-head data. In GALAXI, ustekinumab was a reference arm.”
There will be further subanalyses of LUCENT-1 to come, including results from endoscopy and histology investigations, and the maintenance trial LUCENT-2 will also report soon.
“The feeling is that IL23 blockade is more specific, [more] beneficial in inflammatory bowel disease than blocking both IL12 and IL23,” Dr. D’Haens said.
Dr. D’Haens was an investigator in the LUCENT-1 trial and has acted as an adviser to the study’s sponsor, Eli Lilly, among many other big pharma companies. Dr. Bettenworth is on the advisory board or is a consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, Else Kröner-Fresenius-Foundation, Galapagos, Guidepoint, Impulze, Falk Foundation, Ferring, Janssen Cilag, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, and Vifor Pharma.
Mirikizumab is the first interleukin (IL) 23p19 to report positive phase 3 results for induction therapy in patients who have moderate to severe ulcerative colitis (UC) and have already been treated with at least one prior therapy.
Compared to placebo, almost a quarter (24.2%) of patients treated with mirikizumab versus 13% of those treated with placebo were in clinical remission at the end of the 12-week LUCENT-1 study. This was the study’s primary endpoint and it was a significant result (P = .00006), study investigator Geert D’Haens, MD, PhD, reported at the 17th congress of the European Crohn’s and Colitis Organisation.
Moreover, mirikizumab met all its secondary endpoints in the trial. At the end of the study almost two-thirds (63.5%) of patients achieved a clinical response (vs. 42.2% in the placebo arm); over one-third (36.3%) exhibited endoscopic remission (vs. 21.1%), and just over a quarter (27.1% vs. 13.9%) showed histologic-endoscopic mucosal improvement, according to a press release. The P values for all comparisons were less than .00001.
Perhaps more importantly from the patient perspective, there was greater symptomatic improvement and less bowel urgency in those treated with mirikizumab versus those randomized to placebo.
“The results confirmed [the] efficacy and safety noted in the phase 2 induction [trials], and supports mirikizumab’s potential as treatment for ulcerative colitis,” said Dr. D’Haens, professor of gastroenterology and hepatology at Amsterdam University Medical Centers.
Dominik Bettenworth, MD, who was not involved in the study, said that “the positive results from the LUCENT-1 trial are an important step towards selective IL-23 inhibition as a new mode of action for the treatment of patients with UC.
“This treatment approach has been shown efficacious and launched in other immune-mediated diseases such as psoriasis,” said Dr. Bettenworth, a specialist in internal medicine and gastroenterology in Münster, Germany.
“Noteworthy, for the first time in a phase 3 trial in IBD, [bowel] urgency has been assessed as a secondary endpoint – a clinical symptom of particular importance for patients with UC,” he added, noting that regarding safety, “the LUCENT-1 trial further confirms the previously observed overall good safety profile of IL-23 inhibitors.”
About mirikizumab and LUCENT-1
Mirikizumab is a humanized monoclonal antibody directed against the p19 subunit of IL-23 and is one of several IL23p19 antibodies currently under investigation for the treatment of IBD.
LUCENT-1 was a multicenter, randomized, double-blind, parallel group, placebo-controlled induction study in just over 1,200 patients aged 18-80 years. For inclusion, patients had to have moderately to severely active UC and had to have received at least one prior therapy, but had an inadequate or loss of response to it or been intolerant of it. Baseline data showed that 40% of patients included had been treated with corticosteroids and 24% with immunomodulators, and any current treatment remained unchanged during the study. Biologic treatment had failed in about 40% of patients and any patient taking such therapy had to discontinue it before participating in the trial.
Patients were randomized to receive 300 mg of mirikizumab or matching placebo, given intravenously at weeks 0, 4, and 8. Dr. D’Haens noted that randomization had been in a 3:1 ratio and had been stratified according to various factors such as biologic failure status, corticosteroid use, baseline disease activity, and region of the world where the patient was recruited.
Better results if biologic naive
Clinical remission was stringently defined as: Mayo stool frequency subscore of zero or one, with a reduction of one point or greater from baseline; no rectal bleeding; and a Mayo endoscopic subscore of zero to one. When looking at this primary endpoint in terms of whether patients had received prior biologic treatment, there was a higher remission rate at week 12 if patients had not previously been given any biologic therapy than if they had, but rates were still higher than placebo (30.9% vs. 15.8% and 15.2% vs. 8.5%, respectively), according to the press release. The P value was less than .001 for both comparisons although the study was not powered to look at these subgroups of patients.
Similarly, for clinical response – which was a decrease in the modified Mayo score of 2 or more points and at least a 30% decrease from initial values, as well as a decrease in rectal bleeding – there were differences between patients who had (54.6% for mirikizumab vs. 29.7% for placebo) and had not (70.1% vs. 50.3%) received a biologic previously (again, P less than .001 for both comparisons).
“Control of bowel function is one of the most debilitating, or one of the most important features for patients with ulcerative colitis,” Dr. D’Haens said when presenting the data on bowel urgency. In the trial there was an improvement in urgency – which was rated by patients – starting as early as week 2, with further improvement seen as the induction period went on.
Mirikizumab safety consistent with other trials
Dr. D’Haens noted that the safety profile of IL23 antibodies was “extremely clean.” As with other trials of mirikizumab, he said, there were similar or lower rates to placebo for many adverse events including any infection (15.1% vs. 14%) and cerebrocardiovascular events (0.6% vs. 0.1%). The overall rate of treatment emergent adverse events was 44.5% vs. 46.1% for mirikizumab and placebo. Notably, there were fewer serious adverse events (2.8% vs. 5.3%.) and discontinuations because of side effects (1.6% vs. 7.2%) in the mirikizumab group.
Are gastroenterologists now spoiled for choice?
Lots of questions followed Dr. D’Haens presentation, many picking up on the high placebo response and remission rates.
“We’ve seen it in a number of trials now,” Dr. D’Haens said. “One of the reasons is that patients are allowed to start corticosteroids as late as 2 weeks before randomization,” he observed. In LUCENT-1, half of the patients that were using steroids were receiving a dose of 20 mg of prednisone.
“Now when you start 20 mg of prednisone 2 weeks before randomization that might have an impact on your placebo readout. So I think that’s a lesson for many more trials in the future,” Dr. D’Haens said,”
A high placebo response rate was not expected and another hypothesis is that maybe additional clinical support for fatigue that was received may have played a role.
Several delegates asked for guidance on where mirikizumab and other IL-23p19 blockers might now fit in the grand scheme of patient treatment.
“It is really nice to have expanding therapeutic options but how will we choose?” said one in the online Q&A. “Which IL23 antagonist should we be using now?” and “Is ustekinumab obsolete in UC?” asked others.
“I think it’s early days to decide where the field is going,” Dr. D’Haens said after his presentation. “We don’t have head-to-head data. In GALAXI, ustekinumab was a reference arm.”
There will be further subanalyses of LUCENT-1 to come, including results from endoscopy and histology investigations, and the maintenance trial LUCENT-2 will also report soon.
“The feeling is that IL23 blockade is more specific, [more] beneficial in inflammatory bowel disease than blocking both IL12 and IL23,” Dr. D’Haens said.
Dr. D’Haens was an investigator in the LUCENT-1 trial and has acted as an adviser to the study’s sponsor, Eli Lilly, among many other big pharma companies. Dr. Bettenworth is on the advisory board or is a consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, Else Kröner-Fresenius-Foundation, Galapagos, Guidepoint, Impulze, Falk Foundation, Ferring, Janssen Cilag, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, and Vifor Pharma.
Mirikizumab is the first interleukin (IL) 23p19 to report positive phase 3 results for induction therapy in patients who have moderate to severe ulcerative colitis (UC) and have already been treated with at least one prior therapy.
Compared to placebo, almost a quarter (24.2%) of patients treated with mirikizumab versus 13% of those treated with placebo were in clinical remission at the end of the 12-week LUCENT-1 study. This was the study’s primary endpoint and it was a significant result (P = .00006), study investigator Geert D’Haens, MD, PhD, reported at the 17th congress of the European Crohn’s and Colitis Organisation.
Moreover, mirikizumab met all its secondary endpoints in the trial. At the end of the study almost two-thirds (63.5%) of patients achieved a clinical response (vs. 42.2% in the placebo arm); over one-third (36.3%) exhibited endoscopic remission (vs. 21.1%), and just over a quarter (27.1% vs. 13.9%) showed histologic-endoscopic mucosal improvement, according to a press release. The P values for all comparisons were less than .00001.
Perhaps more importantly from the patient perspective, there was greater symptomatic improvement and less bowel urgency in those treated with mirikizumab versus those randomized to placebo.
“The results confirmed [the] efficacy and safety noted in the phase 2 induction [trials], and supports mirikizumab’s potential as treatment for ulcerative colitis,” said Dr. D’Haens, professor of gastroenterology and hepatology at Amsterdam University Medical Centers.
Dominik Bettenworth, MD, who was not involved in the study, said that “the positive results from the LUCENT-1 trial are an important step towards selective IL-23 inhibition as a new mode of action for the treatment of patients with UC.
“This treatment approach has been shown efficacious and launched in other immune-mediated diseases such as psoriasis,” said Dr. Bettenworth, a specialist in internal medicine and gastroenterology in Münster, Germany.
“Noteworthy, for the first time in a phase 3 trial in IBD, [bowel] urgency has been assessed as a secondary endpoint – a clinical symptom of particular importance for patients with UC,” he added, noting that regarding safety, “the LUCENT-1 trial further confirms the previously observed overall good safety profile of IL-23 inhibitors.”
About mirikizumab and LUCENT-1
Mirikizumab is a humanized monoclonal antibody directed against the p19 subunit of IL-23 and is one of several IL23p19 antibodies currently under investigation for the treatment of IBD.
LUCENT-1 was a multicenter, randomized, double-blind, parallel group, placebo-controlled induction study in just over 1,200 patients aged 18-80 years. For inclusion, patients had to have moderately to severely active UC and had to have received at least one prior therapy, but had an inadequate or loss of response to it or been intolerant of it. Baseline data showed that 40% of patients included had been treated with corticosteroids and 24% with immunomodulators, and any current treatment remained unchanged during the study. Biologic treatment had failed in about 40% of patients and any patient taking such therapy had to discontinue it before participating in the trial.
Patients were randomized to receive 300 mg of mirikizumab or matching placebo, given intravenously at weeks 0, 4, and 8. Dr. D’Haens noted that randomization had been in a 3:1 ratio and had been stratified according to various factors such as biologic failure status, corticosteroid use, baseline disease activity, and region of the world where the patient was recruited.
Better results if biologic naive
Clinical remission was stringently defined as: Mayo stool frequency subscore of zero or one, with a reduction of one point or greater from baseline; no rectal bleeding; and a Mayo endoscopic subscore of zero to one. When looking at this primary endpoint in terms of whether patients had received prior biologic treatment, there was a higher remission rate at week 12 if patients had not previously been given any biologic therapy than if they had, but rates were still higher than placebo (30.9% vs. 15.8% and 15.2% vs. 8.5%, respectively), according to the press release. The P value was less than .001 for both comparisons although the study was not powered to look at these subgroups of patients.
Similarly, for clinical response – which was a decrease in the modified Mayo score of 2 or more points and at least a 30% decrease from initial values, as well as a decrease in rectal bleeding – there were differences between patients who had (54.6% for mirikizumab vs. 29.7% for placebo) and had not (70.1% vs. 50.3%) received a biologic previously (again, P less than .001 for both comparisons).
“Control of bowel function is one of the most debilitating, or one of the most important features for patients with ulcerative colitis,” Dr. D’Haens said when presenting the data on bowel urgency. In the trial there was an improvement in urgency – which was rated by patients – starting as early as week 2, with further improvement seen as the induction period went on.
Mirikizumab safety consistent with other trials
Dr. D’Haens noted that the safety profile of IL23 antibodies was “extremely clean.” As with other trials of mirikizumab, he said, there were similar or lower rates to placebo for many adverse events including any infection (15.1% vs. 14%) and cerebrocardiovascular events (0.6% vs. 0.1%). The overall rate of treatment emergent adverse events was 44.5% vs. 46.1% for mirikizumab and placebo. Notably, there were fewer serious adverse events (2.8% vs. 5.3%.) and discontinuations because of side effects (1.6% vs. 7.2%) in the mirikizumab group.
Are gastroenterologists now spoiled for choice?
Lots of questions followed Dr. D’Haens presentation, many picking up on the high placebo response and remission rates.
“We’ve seen it in a number of trials now,” Dr. D’Haens said. “One of the reasons is that patients are allowed to start corticosteroids as late as 2 weeks before randomization,” he observed. In LUCENT-1, half of the patients that were using steroids were receiving a dose of 20 mg of prednisone.
“Now when you start 20 mg of prednisone 2 weeks before randomization that might have an impact on your placebo readout. So I think that’s a lesson for many more trials in the future,” Dr. D’Haens said,”
A high placebo response rate was not expected and another hypothesis is that maybe additional clinical support for fatigue that was received may have played a role.
Several delegates asked for guidance on where mirikizumab and other IL-23p19 blockers might now fit in the grand scheme of patient treatment.
“It is really nice to have expanding therapeutic options but how will we choose?” said one in the online Q&A. “Which IL23 antagonist should we be using now?” and “Is ustekinumab obsolete in UC?” asked others.
“I think it’s early days to decide where the field is going,” Dr. D’Haens said after his presentation. “We don’t have head-to-head data. In GALAXI, ustekinumab was a reference arm.”
There will be further subanalyses of LUCENT-1 to come, including results from endoscopy and histology investigations, and the maintenance trial LUCENT-2 will also report soon.
“The feeling is that IL23 blockade is more specific, [more] beneficial in inflammatory bowel disease than blocking both IL12 and IL23,” Dr. D’Haens said.
Dr. D’Haens was an investigator in the LUCENT-1 trial and has acted as an adviser to the study’s sponsor, Eli Lilly, among many other big pharma companies. Dr. Bettenworth is on the advisory board or is a consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, Else Kröner-Fresenius-Foundation, Galapagos, Guidepoint, Impulze, Falk Foundation, Ferring, Janssen Cilag, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, and Vifor Pharma.
FROM ECCO 2022
‘Superdonor’ samples don’t increase FMT success in ulcerative colitis
The success of fecal microbiota transplantation (FMT) in people with active ulcerative colitis (UC) was not improved by using highly standardized and controlled “superdonor” samples versus control samples, according to results reported at the 17th congress of the European Crohn’s and Colitis Organisation.
Indeed, a similar percentage (10% and 13.9%, respectively; P = .72) of patients achieved combined steroid-free endoscopic and clinical remission at 8 weeks, which was the primary endpoint of the randomized, controlled, RESTORE-UC trial.
“Maybe we were too bold to say we will go for steroid-free endoscopic remission and response,” said Clara Caenepeel, MD, who was the presenting study investigator. “It’s a very strict endpoint.”
The reasoning for such a strict endpoint, however, was so that the trials’ findings could be compared with some of the other studies that have been done with FMT in UC. Importantly, all those trials have all been positive, making the results of the RESTORE-UC trial at odds with their findings.
“I think in the analysis that we will do now is definitely look at how many steps we went into the right direction,” noted Dr. Caenepeel, who is a doctoral researcher at IBD Leuven (Belgium).
Response to results
Although this is a negative trial, its findings are still important for future work looking at the role of FMT in managing patients with inflammatory bowel disease and identifying the best donor material and ways to deliver it.
While some have suggested it was back to the bench to explore negative results, others such as Michael A. Kamm, MBBS, MD, FRCP, FRACP, congratulated the investigators for undertaking the study, saying that “these studies are very hard to do!”
Dr. Kamm, who is professor of gastroenterology and leads the Kamm Gut Research Group at the University of Melbourne, was part of the Australian team that conducted the FOCUS (Faecal Microbiota Transplantation in Ulcerative Colitis) study. That study used the same primary endpoint of steroid-free endoscopic and clinical remission at 8 weeks but reported positive results – 27% of patients who had FMT versus just 8% of those who had a saline enema as a placebo achieved the endpoint (P = .021). Similarly positive findings have also been reported from five other studies.
“To understand why [RESTORE-UC] study is negative, coming after several positive studies, one needs to explore the differences in study design,” Dr. Kamm observed in an interview. Those differences include how donors were selected, how the FMT was delivered, and how patients were selected.
“All the early studies made no presumption about a favorable donor profile,” Dr. Kamm noted with regard to the selection of donors based on their microbial profile. Moreover “the mode of delivery – sigmoidoscopy without any colonoscopic whole-colon delivery, in contrast to previous studies – as well as patient selection, [with] no information on the anatomical extent of their disease,” could be important.
“There are enough robust positive studies of FMT in ulcerative colitis to believe that this therapy can be effective,” said Dr. Kamm. “Analysis of negative studies like this one should help us to understand what factors are needed to achieve a positive outcome.”
RESTORE-UC trial
“Fecal microbiota transplantation is a new emerging strategy in the treatment of active ulcerative colitis,” Dr. Caenepeel observed during her presentation. At the time the study was started in 2017 there had been four other studies, with “very heterogeneous” designs in terms of the samples used, the placebos given, the delivery of FMT, and the primary endpoints. The idea of superdonor samples also came out of those trials.
So the aim was to try to standardize practice and set up a trial “to examine if we could increase the FMT success rate in our active ulcerative colitis patients by strictly preselecting our donors; by standardized FMT preparation; and a standardized and repeated FMT administration,” Dr. Caenepeel said.
RESTORE-UC was a multicenter, randomized, double-blind, and sham-controlled trial conducted in seven Belgian hospitals. A predefined futility analysis was performed when 66% (n = 72) of the proposed 108 patients had been recruited. Of these, 36 receive autologous FMT and 30 received superdonor FMT.
“We put the emphasis on standardization. This started already with our donor selection,” Dr. Caenepeel said. From a potential 57 healthy donors, 15 were selected and altogether provided more than 500 samples that were then whittled down to the ones that provided the “best” microbial content.
FMT or autologous samples delivered four times – first by sigmoidoscopy and then at weekly intervals by rectal enema. Every patient received the same donor material, Dr. Caenepeel stressed, containing the same enterotype and concentration.
In addition to the primary endpoint of steroid-free endoscopic and clinical remission at Week 8, secondary endpoints included steroid-free clinical remission, steroid-free clinical response, steroid-free endoscopic remission, and steroid-free endoscopic response. Again, however, no significant differences were seen between the two study arms.
Two serious adverse events were seen in the trial, both occurring in the autologous sample group; these were dysuria/constipation and a worsening of colitis that needed surgery.
In discussion, Walter Reinisch, MD, the director of the inflammatory bowel disease study group at the Medical University of Vienna, picked up on why the study may have been negative. He observed that using a steroid-free endoscopic endpoint, where the Mayo score was zero, may have been a factor. A result of 19% at week 8 was not insignificant, he said, observing “if studies from big sponsors would get these results, they would be very happy.”
Perhaps the trials to date have been a little too simplistic by looking at the donor’s microbiota, Dr. Caenepeel. “It goes much further than microbiota,” she said. Thus, future work will perhaps look at the genetics and immunity of those undergoing FMT, she suggested.
Dr. Caenepeel, Dr. Kamm, and Dr. Reinisch had no conflicts of interest to disclose.
The success of fecal microbiota transplantation (FMT) in people with active ulcerative colitis (UC) was not improved by using highly standardized and controlled “superdonor” samples versus control samples, according to results reported at the 17th congress of the European Crohn’s and Colitis Organisation.
Indeed, a similar percentage (10% and 13.9%, respectively; P = .72) of patients achieved combined steroid-free endoscopic and clinical remission at 8 weeks, which was the primary endpoint of the randomized, controlled, RESTORE-UC trial.
“Maybe we were too bold to say we will go for steroid-free endoscopic remission and response,” said Clara Caenepeel, MD, who was the presenting study investigator. “It’s a very strict endpoint.”
The reasoning for such a strict endpoint, however, was so that the trials’ findings could be compared with some of the other studies that have been done with FMT in UC. Importantly, all those trials have all been positive, making the results of the RESTORE-UC trial at odds with their findings.
“I think in the analysis that we will do now is definitely look at how many steps we went into the right direction,” noted Dr. Caenepeel, who is a doctoral researcher at IBD Leuven (Belgium).
Response to results
Although this is a negative trial, its findings are still important for future work looking at the role of FMT in managing patients with inflammatory bowel disease and identifying the best donor material and ways to deliver it.
While some have suggested it was back to the bench to explore negative results, others such as Michael A. Kamm, MBBS, MD, FRCP, FRACP, congratulated the investigators for undertaking the study, saying that “these studies are very hard to do!”
Dr. Kamm, who is professor of gastroenterology and leads the Kamm Gut Research Group at the University of Melbourne, was part of the Australian team that conducted the FOCUS (Faecal Microbiota Transplantation in Ulcerative Colitis) study. That study used the same primary endpoint of steroid-free endoscopic and clinical remission at 8 weeks but reported positive results – 27% of patients who had FMT versus just 8% of those who had a saline enema as a placebo achieved the endpoint (P = .021). Similarly positive findings have also been reported from five other studies.
“To understand why [RESTORE-UC] study is negative, coming after several positive studies, one needs to explore the differences in study design,” Dr. Kamm observed in an interview. Those differences include how donors were selected, how the FMT was delivered, and how patients were selected.
“All the early studies made no presumption about a favorable donor profile,” Dr. Kamm noted with regard to the selection of donors based on their microbial profile. Moreover “the mode of delivery – sigmoidoscopy without any colonoscopic whole-colon delivery, in contrast to previous studies – as well as patient selection, [with] no information on the anatomical extent of their disease,” could be important.
“There are enough robust positive studies of FMT in ulcerative colitis to believe that this therapy can be effective,” said Dr. Kamm. “Analysis of negative studies like this one should help us to understand what factors are needed to achieve a positive outcome.”
RESTORE-UC trial
“Fecal microbiota transplantation is a new emerging strategy in the treatment of active ulcerative colitis,” Dr. Caenepeel observed during her presentation. At the time the study was started in 2017 there had been four other studies, with “very heterogeneous” designs in terms of the samples used, the placebos given, the delivery of FMT, and the primary endpoints. The idea of superdonor samples also came out of those trials.
So the aim was to try to standardize practice and set up a trial “to examine if we could increase the FMT success rate in our active ulcerative colitis patients by strictly preselecting our donors; by standardized FMT preparation; and a standardized and repeated FMT administration,” Dr. Caenepeel said.
RESTORE-UC was a multicenter, randomized, double-blind, and sham-controlled trial conducted in seven Belgian hospitals. A predefined futility analysis was performed when 66% (n = 72) of the proposed 108 patients had been recruited. Of these, 36 receive autologous FMT and 30 received superdonor FMT.
“We put the emphasis on standardization. This started already with our donor selection,” Dr. Caenepeel said. From a potential 57 healthy donors, 15 were selected and altogether provided more than 500 samples that were then whittled down to the ones that provided the “best” microbial content.
FMT or autologous samples delivered four times – first by sigmoidoscopy and then at weekly intervals by rectal enema. Every patient received the same donor material, Dr. Caenepeel stressed, containing the same enterotype and concentration.
In addition to the primary endpoint of steroid-free endoscopic and clinical remission at Week 8, secondary endpoints included steroid-free clinical remission, steroid-free clinical response, steroid-free endoscopic remission, and steroid-free endoscopic response. Again, however, no significant differences were seen between the two study arms.
Two serious adverse events were seen in the trial, both occurring in the autologous sample group; these were dysuria/constipation and a worsening of colitis that needed surgery.
In discussion, Walter Reinisch, MD, the director of the inflammatory bowel disease study group at the Medical University of Vienna, picked up on why the study may have been negative. He observed that using a steroid-free endoscopic endpoint, where the Mayo score was zero, may have been a factor. A result of 19% at week 8 was not insignificant, he said, observing “if studies from big sponsors would get these results, they would be very happy.”
Perhaps the trials to date have been a little too simplistic by looking at the donor’s microbiota, Dr. Caenepeel. “It goes much further than microbiota,” she said. Thus, future work will perhaps look at the genetics and immunity of those undergoing FMT, she suggested.
Dr. Caenepeel, Dr. Kamm, and Dr. Reinisch had no conflicts of interest to disclose.
The success of fecal microbiota transplantation (FMT) in people with active ulcerative colitis (UC) was not improved by using highly standardized and controlled “superdonor” samples versus control samples, according to results reported at the 17th congress of the European Crohn’s and Colitis Organisation.
Indeed, a similar percentage (10% and 13.9%, respectively; P = .72) of patients achieved combined steroid-free endoscopic and clinical remission at 8 weeks, which was the primary endpoint of the randomized, controlled, RESTORE-UC trial.
“Maybe we were too bold to say we will go for steroid-free endoscopic remission and response,” said Clara Caenepeel, MD, who was the presenting study investigator. “It’s a very strict endpoint.”
The reasoning for such a strict endpoint, however, was so that the trials’ findings could be compared with some of the other studies that have been done with FMT in UC. Importantly, all those trials have all been positive, making the results of the RESTORE-UC trial at odds with their findings.
“I think in the analysis that we will do now is definitely look at how many steps we went into the right direction,” noted Dr. Caenepeel, who is a doctoral researcher at IBD Leuven (Belgium).
Response to results
Although this is a negative trial, its findings are still important for future work looking at the role of FMT in managing patients with inflammatory bowel disease and identifying the best donor material and ways to deliver it.
While some have suggested it was back to the bench to explore negative results, others such as Michael A. Kamm, MBBS, MD, FRCP, FRACP, congratulated the investigators for undertaking the study, saying that “these studies are very hard to do!”
Dr. Kamm, who is professor of gastroenterology and leads the Kamm Gut Research Group at the University of Melbourne, was part of the Australian team that conducted the FOCUS (Faecal Microbiota Transplantation in Ulcerative Colitis) study. That study used the same primary endpoint of steroid-free endoscopic and clinical remission at 8 weeks but reported positive results – 27% of patients who had FMT versus just 8% of those who had a saline enema as a placebo achieved the endpoint (P = .021). Similarly positive findings have also been reported from five other studies.
“To understand why [RESTORE-UC] study is negative, coming after several positive studies, one needs to explore the differences in study design,” Dr. Kamm observed in an interview. Those differences include how donors were selected, how the FMT was delivered, and how patients were selected.
“All the early studies made no presumption about a favorable donor profile,” Dr. Kamm noted with regard to the selection of donors based on their microbial profile. Moreover “the mode of delivery – sigmoidoscopy without any colonoscopic whole-colon delivery, in contrast to previous studies – as well as patient selection, [with] no information on the anatomical extent of their disease,” could be important.
“There are enough robust positive studies of FMT in ulcerative colitis to believe that this therapy can be effective,” said Dr. Kamm. “Analysis of negative studies like this one should help us to understand what factors are needed to achieve a positive outcome.”
RESTORE-UC trial
“Fecal microbiota transplantation is a new emerging strategy in the treatment of active ulcerative colitis,” Dr. Caenepeel observed during her presentation. At the time the study was started in 2017 there had been four other studies, with “very heterogeneous” designs in terms of the samples used, the placebos given, the delivery of FMT, and the primary endpoints. The idea of superdonor samples also came out of those trials.
So the aim was to try to standardize practice and set up a trial “to examine if we could increase the FMT success rate in our active ulcerative colitis patients by strictly preselecting our donors; by standardized FMT preparation; and a standardized and repeated FMT administration,” Dr. Caenepeel said.
RESTORE-UC was a multicenter, randomized, double-blind, and sham-controlled trial conducted in seven Belgian hospitals. A predefined futility analysis was performed when 66% (n = 72) of the proposed 108 patients had been recruited. Of these, 36 receive autologous FMT and 30 received superdonor FMT.
“We put the emphasis on standardization. This started already with our donor selection,” Dr. Caenepeel said. From a potential 57 healthy donors, 15 were selected and altogether provided more than 500 samples that were then whittled down to the ones that provided the “best” microbial content.
FMT or autologous samples delivered four times – first by sigmoidoscopy and then at weekly intervals by rectal enema. Every patient received the same donor material, Dr. Caenepeel stressed, containing the same enterotype and concentration.
In addition to the primary endpoint of steroid-free endoscopic and clinical remission at Week 8, secondary endpoints included steroid-free clinical remission, steroid-free clinical response, steroid-free endoscopic remission, and steroid-free endoscopic response. Again, however, no significant differences were seen between the two study arms.
Two serious adverse events were seen in the trial, both occurring in the autologous sample group; these were dysuria/constipation and a worsening of colitis that needed surgery.
In discussion, Walter Reinisch, MD, the director of the inflammatory bowel disease study group at the Medical University of Vienna, picked up on why the study may have been negative. He observed that using a steroid-free endoscopic endpoint, where the Mayo score was zero, may have been a factor. A result of 19% at week 8 was not insignificant, he said, observing “if studies from big sponsors would get these results, they would be very happy.”
Perhaps the trials to date have been a little too simplistic by looking at the donor’s microbiota, Dr. Caenepeel. “It goes much further than microbiota,” she said. Thus, future work will perhaps look at the genetics and immunity of those undergoing FMT, she suggested.
Dr. Caenepeel, Dr. Kamm, and Dr. Reinisch had no conflicts of interest to disclose.
FROM ECCO 2022
More exercise for people with hemophilia, experts advise
Clinicians should do more to encourage people with hemophilia to undertake regular physical activity and sporting activities, a panel of Italian experts has advised.
they wrote in a consensus paper published in Blood Transfusion.
Physical activity is not only recommended by the World Federation of Hemophilia for people with this bleeding disorder, but also recommended for everyone, depending on their age, by the World Health Organization.
People with hemophilia “are not exempt” from the WHO recommendations, noted Dr. Chiara Biasoli of the unit of transfusion medicine and Centre for Inherited Bleeding Disorders, Maurizio Bufalini Hospital in Cesena, Italy, and fellow expert panel members.
MEMO expert consensus project
To help clinicians decide when and how to recommend physical exercise to people with hemophilia, Dr. Biasoli and colleagues initiated the MEMO (Movement for Persons With Haemophilia) expert consensus project. The aim was to offer some clear practical guidance for routine practice.
The project began with a core group of 11 hemophilia experts meeting virtually in early 2020 because of the COVID-19 pandemic. The MEMO scientific committee, as they became known, formulated a set of consensus statements which they then put before members of the Italian Association of Hemophilia Centres, asking them to vote online on their level of agreement with each statement.
A modified Delphi approach was used to reach a consensus, with statements that scored 7 or higher on a 9-point rating scale moving forward into the next round of voting. A total of three voting rounds was made, which took into account the views of 40 experts, overall.
Overview of the MEMO consensus statements
The MEMO consensus statements cover three topic areas: the first four statements focus on the impact of hemophilia on movement, the next three give physical activity recommendations, and the final three look at choice and management of sporting activities.
Regarding the impact of hemophilia on movement, Dr. Biasoli and colleagues noted that “overweight and obesity are an increasing problem in PwH” and, due to their known association with poor physical health, urgently need to be addressed.
Perhaps “insufficient education by hematologists and other invoiced specialists” is at play, they suggested. Importantly, in children, “parents’ fears with consequent overprotection” may be contributing factors.
Not only is movement beneficial for improving joint function, they stated, but it’s also crucial to improving bone density and reducing the risk of joint bleeds.
Even people with inhibitors should be encouraged to be active more regularly, the expert panel said. This should of course be done with “particular caution and monitoring of the effectiveness of prophylaxis for the prevention of acute bleeding events, so that physical activity is conducted safely.”
The panel’s recommendations on sporting activities include the advice to work in a multidisciplinary team that involves hematologists, musculoskeletal specialists and specialists in sports medicine, with the latter helping decide on what sporting activity might be most appropriate. They also suggest that participation in sport should be encouraged from a young age, noting that the Canadian Hemophilia Society has issued some good tips in that regard.
Alongside the recommendations the MEMO expert panel has created four “pyramids of movement” to help clinicians visualize and discuss the recommendations with their patients.
“Physical activity can be considered as a low price intervention that can prevent/reduce the occurrence of chronic diseases and should be further encouraged,” Dr. Biasoli and fellow MEMO expert panel members concluded.
The members of the MEMO expert panel disclosed multiple financial ties with pharmaceutical companies, but none are relevant to the recommendations they made.
Clinicians should do more to encourage people with hemophilia to undertake regular physical activity and sporting activities, a panel of Italian experts has advised.
they wrote in a consensus paper published in Blood Transfusion.
Physical activity is not only recommended by the World Federation of Hemophilia for people with this bleeding disorder, but also recommended for everyone, depending on their age, by the World Health Organization.
People with hemophilia “are not exempt” from the WHO recommendations, noted Dr. Chiara Biasoli of the unit of transfusion medicine and Centre for Inherited Bleeding Disorders, Maurizio Bufalini Hospital in Cesena, Italy, and fellow expert panel members.
MEMO expert consensus project
To help clinicians decide when and how to recommend physical exercise to people with hemophilia, Dr. Biasoli and colleagues initiated the MEMO (Movement for Persons With Haemophilia) expert consensus project. The aim was to offer some clear practical guidance for routine practice.
The project began with a core group of 11 hemophilia experts meeting virtually in early 2020 because of the COVID-19 pandemic. The MEMO scientific committee, as they became known, formulated a set of consensus statements which they then put before members of the Italian Association of Hemophilia Centres, asking them to vote online on their level of agreement with each statement.
A modified Delphi approach was used to reach a consensus, with statements that scored 7 or higher on a 9-point rating scale moving forward into the next round of voting. A total of three voting rounds was made, which took into account the views of 40 experts, overall.
Overview of the MEMO consensus statements
The MEMO consensus statements cover three topic areas: the first four statements focus on the impact of hemophilia on movement, the next three give physical activity recommendations, and the final three look at choice and management of sporting activities.
Regarding the impact of hemophilia on movement, Dr. Biasoli and colleagues noted that “overweight and obesity are an increasing problem in PwH” and, due to their known association with poor physical health, urgently need to be addressed.
Perhaps “insufficient education by hematologists and other invoiced specialists” is at play, they suggested. Importantly, in children, “parents’ fears with consequent overprotection” may be contributing factors.
Not only is movement beneficial for improving joint function, they stated, but it’s also crucial to improving bone density and reducing the risk of joint bleeds.
Even people with inhibitors should be encouraged to be active more regularly, the expert panel said. This should of course be done with “particular caution and monitoring of the effectiveness of prophylaxis for the prevention of acute bleeding events, so that physical activity is conducted safely.”
The panel’s recommendations on sporting activities include the advice to work in a multidisciplinary team that involves hematologists, musculoskeletal specialists and specialists in sports medicine, with the latter helping decide on what sporting activity might be most appropriate. They also suggest that participation in sport should be encouraged from a young age, noting that the Canadian Hemophilia Society has issued some good tips in that regard.
Alongside the recommendations the MEMO expert panel has created four “pyramids of movement” to help clinicians visualize and discuss the recommendations with their patients.
“Physical activity can be considered as a low price intervention that can prevent/reduce the occurrence of chronic diseases and should be further encouraged,” Dr. Biasoli and fellow MEMO expert panel members concluded.
The members of the MEMO expert panel disclosed multiple financial ties with pharmaceutical companies, but none are relevant to the recommendations they made.
Clinicians should do more to encourage people with hemophilia to undertake regular physical activity and sporting activities, a panel of Italian experts has advised.
they wrote in a consensus paper published in Blood Transfusion.
Physical activity is not only recommended by the World Federation of Hemophilia for people with this bleeding disorder, but also recommended for everyone, depending on their age, by the World Health Organization.
People with hemophilia “are not exempt” from the WHO recommendations, noted Dr. Chiara Biasoli of the unit of transfusion medicine and Centre for Inherited Bleeding Disorders, Maurizio Bufalini Hospital in Cesena, Italy, and fellow expert panel members.
MEMO expert consensus project
To help clinicians decide when and how to recommend physical exercise to people with hemophilia, Dr. Biasoli and colleagues initiated the MEMO (Movement for Persons With Haemophilia) expert consensus project. The aim was to offer some clear practical guidance for routine practice.
The project began with a core group of 11 hemophilia experts meeting virtually in early 2020 because of the COVID-19 pandemic. The MEMO scientific committee, as they became known, formulated a set of consensus statements which they then put before members of the Italian Association of Hemophilia Centres, asking them to vote online on their level of agreement with each statement.
A modified Delphi approach was used to reach a consensus, with statements that scored 7 or higher on a 9-point rating scale moving forward into the next round of voting. A total of three voting rounds was made, which took into account the views of 40 experts, overall.
Overview of the MEMO consensus statements
The MEMO consensus statements cover three topic areas: the first four statements focus on the impact of hemophilia on movement, the next three give physical activity recommendations, and the final three look at choice and management of sporting activities.
Regarding the impact of hemophilia on movement, Dr. Biasoli and colleagues noted that “overweight and obesity are an increasing problem in PwH” and, due to their known association with poor physical health, urgently need to be addressed.
Perhaps “insufficient education by hematologists and other invoiced specialists” is at play, they suggested. Importantly, in children, “parents’ fears with consequent overprotection” may be contributing factors.
Not only is movement beneficial for improving joint function, they stated, but it’s also crucial to improving bone density and reducing the risk of joint bleeds.
Even people with inhibitors should be encouraged to be active more regularly, the expert panel said. This should of course be done with “particular caution and monitoring of the effectiveness of prophylaxis for the prevention of acute bleeding events, so that physical activity is conducted safely.”
The panel’s recommendations on sporting activities include the advice to work in a multidisciplinary team that involves hematologists, musculoskeletal specialists and specialists in sports medicine, with the latter helping decide on what sporting activity might be most appropriate. They also suggest that participation in sport should be encouraged from a young age, noting that the Canadian Hemophilia Society has issued some good tips in that regard.
Alongside the recommendations the MEMO expert panel has created four “pyramids of movement” to help clinicians visualize and discuss the recommendations with their patients.
“Physical activity can be considered as a low price intervention that can prevent/reduce the occurrence of chronic diseases and should be further encouraged,” Dr. Biasoli and fellow MEMO expert panel members concluded.
The members of the MEMO expert panel disclosed multiple financial ties with pharmaceutical companies, but none are relevant to the recommendations they made.
FROM BLOOD TRANSFUSION
What are the cardiorenal differences between type 1 and type 2 diabetes?
While type 2 diabetes is associated with a greater risk for cardiovascular events than type 1 diabetes, the latter is more associated with chronic kidney complications, according to data from a French observational study.
That’s not to say that type 1 diabetes isn’t also associated with poor heart health that is of concern, according to Denis Angoulvant, MD, of Tours (France) Regional University Hospital and Trousseau Hospital in Paris.
“The difference is that, in the middle or older ages, we suddenly see a surge of cardiovascular events in type 1 diabetic patients,” he said at the annual meeting of the European Association for the Study of Diabetes. “As a cardiologist, I must say that we are barely see these patients ahead of those complications, so we advocate that there’s a gap to be filled here to prevent these events in these patients.”
Few studies have looked at the comparative risks for cardiovascular and renal outcomes between patients with type 1 and type 2 diabetes, Dr. Angoulvant said, so the aim of the study he presented was to look at this in more detail.
Comparing cardiovascular and renal outcomes
Data from the French hospital discharge database (PMSI), which covers more than 98% of the country’s population, were used to find all adults with type 1 or type 2 diabetes who had at least 5 years of follow-up data starting from 2013.
Not surprisingly, there were eight times as many individuals with type 2 diabetes (425,207) than those with type 1 diabetes (50,623), and patients with type 2 diabetes tended to be older than those with type 1 diabetes (mean age, 68.6 vs. 61.4 years).
There were many significant differences between the two groups of patients in terms of clinical variables, such as patients with type 2 diabetes having more cardiovascular risk factors or preexisting heart problems, and those with type 1 diabetes more likely to have diabetic eye disease.
Indeed, Dr. Angoulvant pointed out that those with type 2 diabetes were significantly more likely (all P < .0001) than those with type 1 diabetes to have: hypertension (70.8% vs. 50.5%), heart failure (35.7% vs. 16.4%), valvular heart disease (7.2% vs. 3.5%), dilated cardiomyopathy (5.5% vs. 2.7%), coronary artery disease (27.6 vs. 18.6%), previous MI (3.0% vs. 2.4%), peripheral vascular disease (22.0% vs. 15.5%), and ischemic stroke (3.3 vs. 2.2%).
“Regarding more specific microvascular diabetic complications, we had a higher incidence of chronic kidney disease in type 2 diabetes patients [10.2% vs. 9.1%], but a higher incidence of diabetic retinopathy in type 1 diabetes patients [6.6% vs. 12.2%],” Dr. Angoulvant said.
Considering more than 2 million person-years of follow-up, the annual rates of MI, new-onset heart failure, ischemic stroke, and chronic kidney disease for the whole study population were respective 1.4%, 5.4%, 1.2%, and 3.4%. The annual rates for death from any cause was 9.7%, and for a cardiovascular reason was 2.4%.
Cardiovascular disease prevalence and event rates
The mean follow-up period was 4.3 years, and over this time the age- and sex-adjusted prevalence of cardiovascular disease was found to be highest in individuals with type 2 diabetes, especially after the age of 40 years.
Looking at the rates of different cardiovascular events showed that both younger (18-29 years) and older (60+ years) people with type 1 diabetes had a 1.2-fold higher risk for MI than similarly aged individuals with type 2 diabetes.
Furthermore, younger and older type 1 diabetes individuals had a 1.1- to 1.4-fold greater risk of new-onset heart failure than those with type 2 diabetes.
“Interestingly, regarding the incidence of ischemic stroke in our population, we found no significant difference between patients with type 1 diabetes, and patients with type 2 diabetes,” Dr. Angoulvant said.
Chronic kidney disease and risk for death
Chronic kidney disease was most common in individuals with type 1 diabetes who were aged between 18 and 69 years, with a greater prevalence also seen in those with type 2 diabetes only after age 80.
The risk of new chronic kidney disease was significantly increased in patients with type 1 diabetes, compared with patients with type 2 diabetes, with a 1.1- to 2.4-fold increase seen, first in individuals aged 18-49 years, and then again after the age of 60 years.
Dr. Angoulvant reported that the risk of dying from any cause was 1.1-fold higher in people with type 1 diabetes, compared with those with type 2 diabetes, but after the age of 60 years.
The risk of death from cardiovascular events was also increased in people with type 1 diabetes, but between the ages of 60 and 69 years.
Asked what his take-home message might be, Dr. Angoulvant stressed the importance of heart failure, in all patients with diabetes but particularly in those with type 1 diabetes.
“I think there is room for improvement in terms of assessing who is going to have heart failure, how to assess heart failure, and more importantly, how to prevent heart failure,” perhaps by “introducing those drugs that have shown tremendous benefit regarding hospitalization, such as [sodium-glucose transporter 2] inhibitors” in patients with type 1 diabetes ahead of the events, he said.
Dr. Angoulvant had no conflicts of interest to disclose.
While type 2 diabetes is associated with a greater risk for cardiovascular events than type 1 diabetes, the latter is more associated with chronic kidney complications, according to data from a French observational study.
That’s not to say that type 1 diabetes isn’t also associated with poor heart health that is of concern, according to Denis Angoulvant, MD, of Tours (France) Regional University Hospital and Trousseau Hospital in Paris.
“The difference is that, in the middle or older ages, we suddenly see a surge of cardiovascular events in type 1 diabetic patients,” he said at the annual meeting of the European Association for the Study of Diabetes. “As a cardiologist, I must say that we are barely see these patients ahead of those complications, so we advocate that there’s a gap to be filled here to prevent these events in these patients.”
Few studies have looked at the comparative risks for cardiovascular and renal outcomes between patients with type 1 and type 2 diabetes, Dr. Angoulvant said, so the aim of the study he presented was to look at this in more detail.
Comparing cardiovascular and renal outcomes
Data from the French hospital discharge database (PMSI), which covers more than 98% of the country’s population, were used to find all adults with type 1 or type 2 diabetes who had at least 5 years of follow-up data starting from 2013.
Not surprisingly, there were eight times as many individuals with type 2 diabetes (425,207) than those with type 1 diabetes (50,623), and patients with type 2 diabetes tended to be older than those with type 1 diabetes (mean age, 68.6 vs. 61.4 years).
There were many significant differences between the two groups of patients in terms of clinical variables, such as patients with type 2 diabetes having more cardiovascular risk factors or preexisting heart problems, and those with type 1 diabetes more likely to have diabetic eye disease.
Indeed, Dr. Angoulvant pointed out that those with type 2 diabetes were significantly more likely (all P < .0001) than those with type 1 diabetes to have: hypertension (70.8% vs. 50.5%), heart failure (35.7% vs. 16.4%), valvular heart disease (7.2% vs. 3.5%), dilated cardiomyopathy (5.5% vs. 2.7%), coronary artery disease (27.6 vs. 18.6%), previous MI (3.0% vs. 2.4%), peripheral vascular disease (22.0% vs. 15.5%), and ischemic stroke (3.3 vs. 2.2%).
“Regarding more specific microvascular diabetic complications, we had a higher incidence of chronic kidney disease in type 2 diabetes patients [10.2% vs. 9.1%], but a higher incidence of diabetic retinopathy in type 1 diabetes patients [6.6% vs. 12.2%],” Dr. Angoulvant said.
Considering more than 2 million person-years of follow-up, the annual rates of MI, new-onset heart failure, ischemic stroke, and chronic kidney disease for the whole study population were respective 1.4%, 5.4%, 1.2%, and 3.4%. The annual rates for death from any cause was 9.7%, and for a cardiovascular reason was 2.4%.
Cardiovascular disease prevalence and event rates
The mean follow-up period was 4.3 years, and over this time the age- and sex-adjusted prevalence of cardiovascular disease was found to be highest in individuals with type 2 diabetes, especially after the age of 40 years.
Looking at the rates of different cardiovascular events showed that both younger (18-29 years) and older (60+ years) people with type 1 diabetes had a 1.2-fold higher risk for MI than similarly aged individuals with type 2 diabetes.
Furthermore, younger and older type 1 diabetes individuals had a 1.1- to 1.4-fold greater risk of new-onset heart failure than those with type 2 diabetes.
“Interestingly, regarding the incidence of ischemic stroke in our population, we found no significant difference between patients with type 1 diabetes, and patients with type 2 diabetes,” Dr. Angoulvant said.
Chronic kidney disease and risk for death
Chronic kidney disease was most common in individuals with type 1 diabetes who were aged between 18 and 69 years, with a greater prevalence also seen in those with type 2 diabetes only after age 80.
The risk of new chronic kidney disease was significantly increased in patients with type 1 diabetes, compared with patients with type 2 diabetes, with a 1.1- to 2.4-fold increase seen, first in individuals aged 18-49 years, and then again after the age of 60 years.
Dr. Angoulvant reported that the risk of dying from any cause was 1.1-fold higher in people with type 1 diabetes, compared with those with type 2 diabetes, but after the age of 60 years.
The risk of death from cardiovascular events was also increased in people with type 1 diabetes, but between the ages of 60 and 69 years.
Asked what his take-home message might be, Dr. Angoulvant stressed the importance of heart failure, in all patients with diabetes but particularly in those with type 1 diabetes.
“I think there is room for improvement in terms of assessing who is going to have heart failure, how to assess heart failure, and more importantly, how to prevent heart failure,” perhaps by “introducing those drugs that have shown tremendous benefit regarding hospitalization, such as [sodium-glucose transporter 2] inhibitors” in patients with type 1 diabetes ahead of the events, he said.
Dr. Angoulvant had no conflicts of interest to disclose.
While type 2 diabetes is associated with a greater risk for cardiovascular events than type 1 diabetes, the latter is more associated with chronic kidney complications, according to data from a French observational study.
That’s not to say that type 1 diabetes isn’t also associated with poor heart health that is of concern, according to Denis Angoulvant, MD, of Tours (France) Regional University Hospital and Trousseau Hospital in Paris.
“The difference is that, in the middle or older ages, we suddenly see a surge of cardiovascular events in type 1 diabetic patients,” he said at the annual meeting of the European Association for the Study of Diabetes. “As a cardiologist, I must say that we are barely see these patients ahead of those complications, so we advocate that there’s a gap to be filled here to prevent these events in these patients.”
Few studies have looked at the comparative risks for cardiovascular and renal outcomes between patients with type 1 and type 2 diabetes, Dr. Angoulvant said, so the aim of the study he presented was to look at this in more detail.
Comparing cardiovascular and renal outcomes
Data from the French hospital discharge database (PMSI), which covers more than 98% of the country’s population, were used to find all adults with type 1 or type 2 diabetes who had at least 5 years of follow-up data starting from 2013.
Not surprisingly, there were eight times as many individuals with type 2 diabetes (425,207) than those with type 1 diabetes (50,623), and patients with type 2 diabetes tended to be older than those with type 1 diabetes (mean age, 68.6 vs. 61.4 years).
There were many significant differences between the two groups of patients in terms of clinical variables, such as patients with type 2 diabetes having more cardiovascular risk factors or preexisting heart problems, and those with type 1 diabetes more likely to have diabetic eye disease.
Indeed, Dr. Angoulvant pointed out that those with type 2 diabetes were significantly more likely (all P < .0001) than those with type 1 diabetes to have: hypertension (70.8% vs. 50.5%), heart failure (35.7% vs. 16.4%), valvular heart disease (7.2% vs. 3.5%), dilated cardiomyopathy (5.5% vs. 2.7%), coronary artery disease (27.6 vs. 18.6%), previous MI (3.0% vs. 2.4%), peripheral vascular disease (22.0% vs. 15.5%), and ischemic stroke (3.3 vs. 2.2%).
“Regarding more specific microvascular diabetic complications, we had a higher incidence of chronic kidney disease in type 2 diabetes patients [10.2% vs. 9.1%], but a higher incidence of diabetic retinopathy in type 1 diabetes patients [6.6% vs. 12.2%],” Dr. Angoulvant said.
Considering more than 2 million person-years of follow-up, the annual rates of MI, new-onset heart failure, ischemic stroke, and chronic kidney disease for the whole study population were respective 1.4%, 5.4%, 1.2%, and 3.4%. The annual rates for death from any cause was 9.7%, and for a cardiovascular reason was 2.4%.
Cardiovascular disease prevalence and event rates
The mean follow-up period was 4.3 years, and over this time the age- and sex-adjusted prevalence of cardiovascular disease was found to be highest in individuals with type 2 diabetes, especially after the age of 40 years.
Looking at the rates of different cardiovascular events showed that both younger (18-29 years) and older (60+ years) people with type 1 diabetes had a 1.2-fold higher risk for MI than similarly aged individuals with type 2 diabetes.
Furthermore, younger and older type 1 diabetes individuals had a 1.1- to 1.4-fold greater risk of new-onset heart failure than those with type 2 diabetes.
“Interestingly, regarding the incidence of ischemic stroke in our population, we found no significant difference between patients with type 1 diabetes, and patients with type 2 diabetes,” Dr. Angoulvant said.
Chronic kidney disease and risk for death
Chronic kidney disease was most common in individuals with type 1 diabetes who were aged between 18 and 69 years, with a greater prevalence also seen in those with type 2 diabetes only after age 80.
The risk of new chronic kidney disease was significantly increased in patients with type 1 diabetes, compared with patients with type 2 diabetes, with a 1.1- to 2.4-fold increase seen, first in individuals aged 18-49 years, and then again after the age of 60 years.
Dr. Angoulvant reported that the risk of dying from any cause was 1.1-fold higher in people with type 1 diabetes, compared with those with type 2 diabetes, but after the age of 60 years.
The risk of death from cardiovascular events was also increased in people with type 1 diabetes, but between the ages of 60 and 69 years.
Asked what his take-home message might be, Dr. Angoulvant stressed the importance of heart failure, in all patients with diabetes but particularly in those with type 1 diabetes.
“I think there is room for improvement in terms of assessing who is going to have heart failure, how to assess heart failure, and more importantly, how to prevent heart failure,” perhaps by “introducing those drugs that have shown tremendous benefit regarding hospitalization, such as [sodium-glucose transporter 2] inhibitors” in patients with type 1 diabetes ahead of the events, he said.
Dr. Angoulvant had no conflicts of interest to disclose.
FROM EASD 2021