User login
AGA Clinical Practice Update: Refer early Barrett’s dysplasia to a specialist
Low-grade esophageal dysplasia must be confirmed by a GI pathologist with a special interest in Barrett’s esophagus, one who deals with the problem on a daily basis and whom peers recognize as an expert in the field, according to a new expert review from the American Gastroenterological Association (Gastroenterology. doi: http://dx.doi.org/10.1053/j.gastro.2016.09.040).
In the absence of reliable biomarkers, it’s the best guarantee that low-grade dysplasia (LGD) is truly present. Overdiagnosis of early dysplasia is common, and it leads to mistreatment and uncertainty about study results, the AGA said.
In the absence of reliable biomarkers, AGA turned to expertise to combat mistreatment. Although it’s clear that high-grade disease and esophageal adenocarcinoma need intervention, LGD sometimes seems to regress on its own, but it’s unclear if it’s due to natural history or diagnosis in patients who don’t really have it.
For now, expertise is the best solution. “Unfortunately, there is no database that clearly identifies experts in the field of Barrett’s esophagus,” but most practitioners can identify people to “refer these patients to within their state or region.” Meanwhile, “we are working tirelessly” to establish a referral and outcome database. “We owe it to” patients to let them know “how good the” people we are referring them to are, Dr. Wani said.
Given the diagnosis uncertainty, AGA side-stepped the biggest controversy in LGD: whether patients should be treated or watched. Among “patients with confirmed Barrett’s esophagus with LGD by expert GI pathology review that persists on a [second] endoscopy despite intensification of acid-suppressive therapy” at 8-12 weeks with proton pump inhibitors twice a day, “risks and benefits of management options of endoscopic eradication therapy (specifically adverse events associated with endoscopic resection and ablation) and ongoing surveillance should be discussed and documented,” the group said.
When patients opt for treatment, endoscopic eradication should proceed “with the goal of achieving complete eradication of intestinal metaplasia ... radiofrequency ablation should be used,” AGA said.
Meanwhile, “patients with LGD undergoing surveillance rather than endoscopic eradication therapy should undergo surveillance every 6 months times two, then annually unless there is reversion to nondysplastic Barrett’s esophagus. Biopsies should be obtained in 4-quadrants every 1-2 cm and of any visible lesions.”
AGA funded the work. Dr. Wani is a Medtronic and Boston Scientific consultant.
Low-grade esophageal dysplasia must be confirmed by a GI pathologist with a special interest in Barrett’s esophagus, one who deals with the problem on a daily basis and whom peers recognize as an expert in the field, according to a new expert review from the American Gastroenterological Association (Gastroenterology. doi: http://dx.doi.org/10.1053/j.gastro.2016.09.040).
In the absence of reliable biomarkers, it’s the best guarantee that low-grade dysplasia (LGD) is truly present. Overdiagnosis of early dysplasia is common, and it leads to mistreatment and uncertainty about study results, the AGA said.
In the absence of reliable biomarkers, AGA turned to expertise to combat mistreatment. Although it’s clear that high-grade disease and esophageal adenocarcinoma need intervention, LGD sometimes seems to regress on its own, but it’s unclear if it’s due to natural history or diagnosis in patients who don’t really have it.
For now, expertise is the best solution. “Unfortunately, there is no database that clearly identifies experts in the field of Barrett’s esophagus,” but most practitioners can identify people to “refer these patients to within their state or region.” Meanwhile, “we are working tirelessly” to establish a referral and outcome database. “We owe it to” patients to let them know “how good the” people we are referring them to are, Dr. Wani said.
Given the diagnosis uncertainty, AGA side-stepped the biggest controversy in LGD: whether patients should be treated or watched. Among “patients with confirmed Barrett’s esophagus with LGD by expert GI pathology review that persists on a [second] endoscopy despite intensification of acid-suppressive therapy” at 8-12 weeks with proton pump inhibitors twice a day, “risks and benefits of management options of endoscopic eradication therapy (specifically adverse events associated with endoscopic resection and ablation) and ongoing surveillance should be discussed and documented,” the group said.
When patients opt for treatment, endoscopic eradication should proceed “with the goal of achieving complete eradication of intestinal metaplasia ... radiofrequency ablation should be used,” AGA said.
Meanwhile, “patients with LGD undergoing surveillance rather than endoscopic eradication therapy should undergo surveillance every 6 months times two, then annually unless there is reversion to nondysplastic Barrett’s esophagus. Biopsies should be obtained in 4-quadrants every 1-2 cm and of any visible lesions.”
AGA funded the work. Dr. Wani is a Medtronic and Boston Scientific consultant.
Low-grade esophageal dysplasia must be confirmed by a GI pathologist with a special interest in Barrett’s esophagus, one who deals with the problem on a daily basis and whom peers recognize as an expert in the field, according to a new expert review from the American Gastroenterological Association (Gastroenterology. doi: http://dx.doi.org/10.1053/j.gastro.2016.09.040).
In the absence of reliable biomarkers, it’s the best guarantee that low-grade dysplasia (LGD) is truly present. Overdiagnosis of early dysplasia is common, and it leads to mistreatment and uncertainty about study results, the AGA said.
In the absence of reliable biomarkers, AGA turned to expertise to combat mistreatment. Although it’s clear that high-grade disease and esophageal adenocarcinoma need intervention, LGD sometimes seems to regress on its own, but it’s unclear if it’s due to natural history or diagnosis in patients who don’t really have it.
For now, expertise is the best solution. “Unfortunately, there is no database that clearly identifies experts in the field of Barrett’s esophagus,” but most practitioners can identify people to “refer these patients to within their state or region.” Meanwhile, “we are working tirelessly” to establish a referral and outcome database. “We owe it to” patients to let them know “how good the” people we are referring them to are, Dr. Wani said.
Given the diagnosis uncertainty, AGA side-stepped the biggest controversy in LGD: whether patients should be treated or watched. Among “patients with confirmed Barrett’s esophagus with LGD by expert GI pathology review that persists on a [second] endoscopy despite intensification of acid-suppressive therapy” at 8-12 weeks with proton pump inhibitors twice a day, “risks and benefits of management options of endoscopic eradication therapy (specifically adverse events associated with endoscopic resection and ablation) and ongoing surveillance should be discussed and documented,” the group said.
When patients opt for treatment, endoscopic eradication should proceed “with the goal of achieving complete eradication of intestinal metaplasia ... radiofrequency ablation should be used,” AGA said.
Meanwhile, “patients with LGD undergoing surveillance rather than endoscopic eradication therapy should undergo surveillance every 6 months times two, then annually unless there is reversion to nondysplastic Barrett’s esophagus. Biopsies should be obtained in 4-quadrants every 1-2 cm and of any visible lesions.”
AGA funded the work. Dr. Wani is a Medtronic and Boston Scientific consultant.
ACP on gout: Treat to symptoms, not to urate targets
New gout treatment guidelines support the use of urate-lowering therapy, but find no place for treating patients to achieve any specific serum urate target – a dichotomy that has some rheumatologists scratching their heads.
Created by the American College of Physicians, the gout diagnosis and treatment guideline doesn’t recommend monitoring physiologic response to urate-lowering therapy or treating to specific serum urate target (Ann Int Med. 2016 Nov 1. doi: 10.7326/M16-0570). Instead, it says patients should be treated according to their symptomatic response – a recommendation that flies in the face of accepted clinical practice.
“When we step back and ask the question, ‘Has a randomized, controlled trial looked at this approach?’ The answer is simply no. And we are not willing to take that leap of faith without data.”
Reliance on lower-grade clinical evidence is simply no longer a strong-enough basis for a clinical practice recommendation, Dr. McLean said in an interview. In 2011, the Institute of Medicine raised the bar for guidelines evidence in its report, “Finding What Works in Health Care: Standards for Systematic Reviews.”
That report explicitly states that a clinical guideline cannot be driven by low-grade evidence, including meta-analysis and expert opinion, Dr. McLean said. The Agency for Healthcare Research and Quality National Guideline Clearinghouse incorporated this into its 2013 revision of guidelines acceptance policy: A review must be based on the highest level of evidence – randomized, controlled studies – and not be driven by expert opinion or review articles. Additionally, the literature reviews upon which guidelines are based must be published in a peer-reviewed journal. Guidelines that don’t meet these criteria will no longer be accepted into the clearinghouse.
“The 2012 ACR guidelines didn’t meet that criteria,” he said. “The authors clearly point out in their methodology section where the evidence is weak and admit that 80% of it is low grade. How can you make a guideline that is 80% based on weak evidence? The ACP doesn’t allow us to do that.”
The argument about whether or not to treat to a specific urate target is not simply philosophical, said Dr. McLean, who authored an accompanying editorial (Ann Int Med. 2016 Nov 1. doi: 10.7326/M16-2401). In it, he argued that treating to a prespecified target would certainly help some patients but would probably hurt others.
“Treating to a target necessarily means increasing doses of medication in patients who may be asymptomatic,” he wrote. “Examples exist from other studies using intermediary biomarkers (such as elevated blood pressure or blood glucose level or low hemoglobin level), in which treating to a target resulted in more adverse effects than benefits. Thus, despite the strong biologic appeal of such a strategy and its advocacy by major specialty society guidelines, we judged the strength of evidence for monitoring to be low.”
“This paradigm also has not been formally tested in a randomized clinical trial, and there’s no scientific evidence to support that strategy and a lot of evidence to show its harm,” she said in an interview. “We have a large clinical experience about the ineffectiveness of that strategy. Patients eventually develop tophi, joint damage, and functional limitations when their physicians only treat their gout flares using anti-inflammatory therapy without addressing their underlying cause of gout – high uric acid. They are often dismayed and upset when they realize their physician had let their gout get to that point by just treating their gout flares.”
In other important ways, the two documents are complementary. Both put NSAIDs, corticosteroids, and colchicine at the heart of treating acute gout attacks.
According to the ACP guideline, these treatment strategies are all supported by high-level evidence, which was drawn from a review of 28 studies.
• Corticosteroids, NSAIDs, and colchicine are effective treatments to reduce pain in patients with acute gout.
• Lower doses of colchicine (1.2 mg, followed by 0.6 mg 1 hour later) are as effective as higher doses (1.2 mg, followed by 0.6 mg/hour for 6 hours) at reducing pain and are associated with fewer gastrointestinal adverse effects.
• Do not initiate long-term uric acid–lowering therapy in most patients after a first gout attack or in patients with infrequent attacks.
• Although evidence supports the benefits of using uric acid–lowering therapy for shorter durations to reduce gout flares, the benefits of long-term use in patients with a single or infrequent gout attacks have not been studied.
• Clinicians should discuss benefits, harms, costs, and individual preferences with patients before initiating uric acid–lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).
• Febuxostat (40 mg/day) and allopurinol (300 mg/day) are equally effective at decreasing serum urate levels, and prophylactic therapy with low-dose colchicine or low-dose NSAIDs reduces the risk for acute gout attacks in patients initiating urate-lowering therapy.
Allopurinol dosage, however, is one key point upon which the ACP and ACR guidelines are sharply divided. The ACR guideline calls for starting at low doses – 100 mg/day, and even lower in patients with kidney disease – with very slow upward titration, only if necessary, to 300 mg/day or more. Allopurinol is not without risk and should be used with caution, Dr. Neogi wrote in her commentary.
“Continuing a management strategy of starting allopurinol at an inappropriately high dose will perpetuate the problem of unnecessarily increasing flare risk, because this risk in the early treatment phase is directly proportional to the potency of the urate-lowering therapy used.”
However, allopurinol doses of 300 mg/day or less leave more than half of all patients undertreated, she said. This dilemma points up the difficulty with symptomatic treatment. Without checking urate levels, clinicians may be shooting blind when trying to dose appropriately.
She refuted any suggestion that the ACR guidelines were based on a lesser degree of evidence than the ACP document.
“The ACR uses a rigorous evidence-based method to develop treatment guidelines. It is inaccurate to say that ACR relies on lower-class evidence or expert opinion ‘to a large extent.’ In the absence of randomized controlled data, other peer-reviewed, available published data are used to formulate guidance, supported by the known biology.”
Current practices outlined in the ACR document are based on a thorough understanding of the biology of gout and how it progresses. Hard data on uric acid targets would greatly impact current therapeutic thinking. But in the meantime, there are patients to be treated, Dr. Neogi said.
“Of course, it would be ideal if we had randomized trial data to definitively provide insights, but we don’t have that right now. So does that mean that patients should suffer unnecessarily because we can’t use the remaining existing body of scientific knowledge to guide rational treatment decisions? What if funding agencies never fund such a study – should gout patients remain poorly managed? Should we abandon all scientific knowledge that isn’t randomized trial data and just not treat at all while waiting to see if a randomized trial will ever be funded and conducted?”
Dr. McLean sees the flip side of that coin.
“I think the effect of our guideline will be to help push the need for more explicit evidence in treat to target being the right way to go. But right now there is not enough evidence now to endorse that approach.”
Dr. McLean reports personal fees from Takeda Pharmaceuticals speakers’ bureau before 2015. Dr. Neogi had no financial disclosures.
New gout treatment guidelines support the use of urate-lowering therapy, but find no place for treating patients to achieve any specific serum urate target – a dichotomy that has some rheumatologists scratching their heads.
Created by the American College of Physicians, the gout diagnosis and treatment guideline doesn’t recommend monitoring physiologic response to urate-lowering therapy or treating to specific serum urate target (Ann Int Med. 2016 Nov 1. doi: 10.7326/M16-0570). Instead, it says patients should be treated according to their symptomatic response – a recommendation that flies in the face of accepted clinical practice.
“When we step back and ask the question, ‘Has a randomized, controlled trial looked at this approach?’ The answer is simply no. And we are not willing to take that leap of faith without data.”
Reliance on lower-grade clinical evidence is simply no longer a strong-enough basis for a clinical practice recommendation, Dr. McLean said in an interview. In 2011, the Institute of Medicine raised the bar for guidelines evidence in its report, “Finding What Works in Health Care: Standards for Systematic Reviews.”
That report explicitly states that a clinical guideline cannot be driven by low-grade evidence, including meta-analysis and expert opinion, Dr. McLean said. The Agency for Healthcare Research and Quality National Guideline Clearinghouse incorporated this into its 2013 revision of guidelines acceptance policy: A review must be based on the highest level of evidence – randomized, controlled studies – and not be driven by expert opinion or review articles. Additionally, the literature reviews upon which guidelines are based must be published in a peer-reviewed journal. Guidelines that don’t meet these criteria will no longer be accepted into the clearinghouse.
“The 2012 ACR guidelines didn’t meet that criteria,” he said. “The authors clearly point out in their methodology section where the evidence is weak and admit that 80% of it is low grade. How can you make a guideline that is 80% based on weak evidence? The ACP doesn’t allow us to do that.”
The argument about whether or not to treat to a specific urate target is not simply philosophical, said Dr. McLean, who authored an accompanying editorial (Ann Int Med. 2016 Nov 1. doi: 10.7326/M16-2401). In it, he argued that treating to a prespecified target would certainly help some patients but would probably hurt others.
“Treating to a target necessarily means increasing doses of medication in patients who may be asymptomatic,” he wrote. “Examples exist from other studies using intermediary biomarkers (such as elevated blood pressure or blood glucose level or low hemoglobin level), in which treating to a target resulted in more adverse effects than benefits. Thus, despite the strong biologic appeal of such a strategy and its advocacy by major specialty society guidelines, we judged the strength of evidence for monitoring to be low.”
“This paradigm also has not been formally tested in a randomized clinical trial, and there’s no scientific evidence to support that strategy and a lot of evidence to show its harm,” she said in an interview. “We have a large clinical experience about the ineffectiveness of that strategy. Patients eventually develop tophi, joint damage, and functional limitations when their physicians only treat their gout flares using anti-inflammatory therapy without addressing their underlying cause of gout – high uric acid. They are often dismayed and upset when they realize their physician had let their gout get to that point by just treating their gout flares.”
In other important ways, the two documents are complementary. Both put NSAIDs, corticosteroids, and colchicine at the heart of treating acute gout attacks.
According to the ACP guideline, these treatment strategies are all supported by high-level evidence, which was drawn from a review of 28 studies.
• Corticosteroids, NSAIDs, and colchicine are effective treatments to reduce pain in patients with acute gout.
• Lower doses of colchicine (1.2 mg, followed by 0.6 mg 1 hour later) are as effective as higher doses (1.2 mg, followed by 0.6 mg/hour for 6 hours) at reducing pain and are associated with fewer gastrointestinal adverse effects.
• Do not initiate long-term uric acid–lowering therapy in most patients after a first gout attack or in patients with infrequent attacks.
• Although evidence supports the benefits of using uric acid–lowering therapy for shorter durations to reduce gout flares, the benefits of long-term use in patients with a single or infrequent gout attacks have not been studied.
• Clinicians should discuss benefits, harms, costs, and individual preferences with patients before initiating uric acid–lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).
• Febuxostat (40 mg/day) and allopurinol (300 mg/day) are equally effective at decreasing serum urate levels, and prophylactic therapy with low-dose colchicine or low-dose NSAIDs reduces the risk for acute gout attacks in patients initiating urate-lowering therapy.
Allopurinol dosage, however, is one key point upon which the ACP and ACR guidelines are sharply divided. The ACR guideline calls for starting at low doses – 100 mg/day, and even lower in patients with kidney disease – with very slow upward titration, only if necessary, to 300 mg/day or more. Allopurinol is not without risk and should be used with caution, Dr. Neogi wrote in her commentary.
“Continuing a management strategy of starting allopurinol at an inappropriately high dose will perpetuate the problem of unnecessarily increasing flare risk, because this risk in the early treatment phase is directly proportional to the potency of the urate-lowering therapy used.”
However, allopurinol doses of 300 mg/day or less leave more than half of all patients undertreated, she said. This dilemma points up the difficulty with symptomatic treatment. Without checking urate levels, clinicians may be shooting blind when trying to dose appropriately.
She refuted any suggestion that the ACR guidelines were based on a lesser degree of evidence than the ACP document.
“The ACR uses a rigorous evidence-based method to develop treatment guidelines. It is inaccurate to say that ACR relies on lower-class evidence or expert opinion ‘to a large extent.’ In the absence of randomized controlled data, other peer-reviewed, available published data are used to formulate guidance, supported by the known biology.”
Current practices outlined in the ACR document are based on a thorough understanding of the biology of gout and how it progresses. Hard data on uric acid targets would greatly impact current therapeutic thinking. But in the meantime, there are patients to be treated, Dr. Neogi said.
“Of course, it would be ideal if we had randomized trial data to definitively provide insights, but we don’t have that right now. So does that mean that patients should suffer unnecessarily because we can’t use the remaining existing body of scientific knowledge to guide rational treatment decisions? What if funding agencies never fund such a study – should gout patients remain poorly managed? Should we abandon all scientific knowledge that isn’t randomized trial data and just not treat at all while waiting to see if a randomized trial will ever be funded and conducted?”
Dr. McLean sees the flip side of that coin.
“I think the effect of our guideline will be to help push the need for more explicit evidence in treat to target being the right way to go. But right now there is not enough evidence now to endorse that approach.”
Dr. McLean reports personal fees from Takeda Pharmaceuticals speakers’ bureau before 2015. Dr. Neogi had no financial disclosures.
New gout treatment guidelines support the use of urate-lowering therapy, but find no place for treating patients to achieve any specific serum urate target – a dichotomy that has some rheumatologists scratching their heads.
Created by the American College of Physicians, the gout diagnosis and treatment guideline doesn’t recommend monitoring physiologic response to urate-lowering therapy or treating to specific serum urate target (Ann Int Med. 2016 Nov 1. doi: 10.7326/M16-0570). Instead, it says patients should be treated according to their symptomatic response – a recommendation that flies in the face of accepted clinical practice.
“When we step back and ask the question, ‘Has a randomized, controlled trial looked at this approach?’ The answer is simply no. And we are not willing to take that leap of faith without data.”
Reliance on lower-grade clinical evidence is simply no longer a strong-enough basis for a clinical practice recommendation, Dr. McLean said in an interview. In 2011, the Institute of Medicine raised the bar for guidelines evidence in its report, “Finding What Works in Health Care: Standards for Systematic Reviews.”
That report explicitly states that a clinical guideline cannot be driven by low-grade evidence, including meta-analysis and expert opinion, Dr. McLean said. The Agency for Healthcare Research and Quality National Guideline Clearinghouse incorporated this into its 2013 revision of guidelines acceptance policy: A review must be based on the highest level of evidence – randomized, controlled studies – and not be driven by expert opinion or review articles. Additionally, the literature reviews upon which guidelines are based must be published in a peer-reviewed journal. Guidelines that don’t meet these criteria will no longer be accepted into the clearinghouse.
“The 2012 ACR guidelines didn’t meet that criteria,” he said. “The authors clearly point out in their methodology section where the evidence is weak and admit that 80% of it is low grade. How can you make a guideline that is 80% based on weak evidence? The ACP doesn’t allow us to do that.”
The argument about whether or not to treat to a specific urate target is not simply philosophical, said Dr. McLean, who authored an accompanying editorial (Ann Int Med. 2016 Nov 1. doi: 10.7326/M16-2401). In it, he argued that treating to a prespecified target would certainly help some patients but would probably hurt others.
“Treating to a target necessarily means increasing doses of medication in patients who may be asymptomatic,” he wrote. “Examples exist from other studies using intermediary biomarkers (such as elevated blood pressure or blood glucose level or low hemoglobin level), in which treating to a target resulted in more adverse effects than benefits. Thus, despite the strong biologic appeal of such a strategy and its advocacy by major specialty society guidelines, we judged the strength of evidence for monitoring to be low.”
“This paradigm also has not been formally tested in a randomized clinical trial, and there’s no scientific evidence to support that strategy and a lot of evidence to show its harm,” she said in an interview. “We have a large clinical experience about the ineffectiveness of that strategy. Patients eventually develop tophi, joint damage, and functional limitations when their physicians only treat their gout flares using anti-inflammatory therapy without addressing their underlying cause of gout – high uric acid. They are often dismayed and upset when they realize their physician had let their gout get to that point by just treating their gout flares.”
In other important ways, the two documents are complementary. Both put NSAIDs, corticosteroids, and colchicine at the heart of treating acute gout attacks.
According to the ACP guideline, these treatment strategies are all supported by high-level evidence, which was drawn from a review of 28 studies.
• Corticosteroids, NSAIDs, and colchicine are effective treatments to reduce pain in patients with acute gout.
• Lower doses of colchicine (1.2 mg, followed by 0.6 mg 1 hour later) are as effective as higher doses (1.2 mg, followed by 0.6 mg/hour for 6 hours) at reducing pain and are associated with fewer gastrointestinal adverse effects.
• Do not initiate long-term uric acid–lowering therapy in most patients after a first gout attack or in patients with infrequent attacks.
• Although evidence supports the benefits of using uric acid–lowering therapy for shorter durations to reduce gout flares, the benefits of long-term use in patients with a single or infrequent gout attacks have not been studied.
• Clinicians should discuss benefits, harms, costs, and individual preferences with patients before initiating uric acid–lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).
• Febuxostat (40 mg/day) and allopurinol (300 mg/day) are equally effective at decreasing serum urate levels, and prophylactic therapy with low-dose colchicine or low-dose NSAIDs reduces the risk for acute gout attacks in patients initiating urate-lowering therapy.
Allopurinol dosage, however, is one key point upon which the ACP and ACR guidelines are sharply divided. The ACR guideline calls for starting at low doses – 100 mg/day, and even lower in patients with kidney disease – with very slow upward titration, only if necessary, to 300 mg/day or more. Allopurinol is not without risk and should be used with caution, Dr. Neogi wrote in her commentary.
“Continuing a management strategy of starting allopurinol at an inappropriately high dose will perpetuate the problem of unnecessarily increasing flare risk, because this risk in the early treatment phase is directly proportional to the potency of the urate-lowering therapy used.”
However, allopurinol doses of 300 mg/day or less leave more than half of all patients undertreated, she said. This dilemma points up the difficulty with symptomatic treatment. Without checking urate levels, clinicians may be shooting blind when trying to dose appropriately.
She refuted any suggestion that the ACR guidelines were based on a lesser degree of evidence than the ACP document.
“The ACR uses a rigorous evidence-based method to develop treatment guidelines. It is inaccurate to say that ACR relies on lower-class evidence or expert opinion ‘to a large extent.’ In the absence of randomized controlled data, other peer-reviewed, available published data are used to formulate guidance, supported by the known biology.”
Current practices outlined in the ACR document are based on a thorough understanding of the biology of gout and how it progresses. Hard data on uric acid targets would greatly impact current therapeutic thinking. But in the meantime, there are patients to be treated, Dr. Neogi said.
“Of course, it would be ideal if we had randomized trial data to definitively provide insights, but we don’t have that right now. So does that mean that patients should suffer unnecessarily because we can’t use the remaining existing body of scientific knowledge to guide rational treatment decisions? What if funding agencies never fund such a study – should gout patients remain poorly managed? Should we abandon all scientific knowledge that isn’t randomized trial data and just not treat at all while waiting to see if a randomized trial will ever be funded and conducted?”
Dr. McLean sees the flip side of that coin.
“I think the effect of our guideline will be to help push the need for more explicit evidence in treat to target being the right way to go. But right now there is not enough evidence now to endorse that approach.”
Dr. McLean reports personal fees from Takeda Pharmaceuticals speakers’ bureau before 2015. Dr. Neogi had no financial disclosures.
Selected liver-transplant patients thrive off immunosuppression
MONTREAL – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.
“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.
Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.
Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”
The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again several times during the subsequent 2 years including assessment of several quality of life measures.
During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.
The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.
Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.
“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.
Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.
Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”
The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again several times during the subsequent 2 years including assessment of several quality of life measures.
During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.
The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.
Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.
“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.
Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.
Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”
The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again several times during the subsequent 2 years including assessment of several quality of life measures.
During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.
The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.
Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point: Selected pediatric liver-transplant patients who successfully weaned off immunosuppression responded with significantly improved quality of life scores.
Major finding: Patient and parent treatment satisfaction improved by 6-7 points when patients stopped immunosuppression and fell by 2-3 points when they did not.
Data source: iWISH, a multicenter study with 88 enrolled patients.
Disclosures: Dr. Mohammad had no disclosures.
Resorbable scaffold appears safe, effective in diabetes patients
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
Key clinical point:
Major finding: The primary endpoint – the rate of target-lesion failure at 1 year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%.
Data source: A prespecified formal substudy of 754 patients with diabetes who participated in three clinical trials and one device registry, assessing 1-year outcomes after PCI.
Disclosures: This pooled analysis, plus all the contributing trials and the device registry, were funded by Abbott Vascular, maker of the resorbable scaffold. Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
Intravitreal sirolimus proves effective in reducing noninfectious uveitis inflammation
Intravitreal sirolimus 440 mcg or 880 mcg administered on days 1, 60, and 120, was shown to significantly improve ocular inflammation with preservation of best-corrected visual acuity in patients with noninfectious uveitis of the posterior segment, a phase III study has shown.
In the multinational SAKURA (Study Assessing Double-masked Uveitis Treatment) study, 346 study eyes were analyzed in this randomly assigned, double-masked, actively controlled study. In the study arm given intravitreal sirolimus 440 mcg, 22.8% (P = .025) met the primary endpoint of no vitreous haze (VH) at month 5 in the study eye without the aid of rescue therapy. In the group given intravitreal sirolimus 880 mcg, 16.4% (P = .182) met the primary endpoint, compared with 10.3% of active controls who were given 44 mcg intravitreal sirolimus.
For the secondary outcome, 52.6% (P = .008) of the intravitreal sirolimus 440 mcg arm had VH scores of 0 or a 0.5+ response rate at month 5. In the intravitreal sirolimus 880 mcg, 43.1% (P = .228) achieved a VH score of 0 or a 0.5+ response rate, compared with 35% of the 44 mcg active control group. Mean best-corrected visual acuity was maintained throughout the study in each study arm, with 76.9% of those who received corticosteroids at baseline in the 440 mcg study arm successfully tapering them to 5 mg per day or less by month 5, and 66.7% of those receiving corticosteroids in the 880 mcg group doing so. This was in comparison with 63.6% of those using corticosteroids in the active control group. Adverse events were similar across the study, and all doses were well tolerated. The study was funded by Santen.
Read the full study in Ophthalmology (2016;23[11]:2413-23).
[email protected]
On Twitter @whitneymcknight
Intravitreal sirolimus 440 mcg or 880 mcg administered on days 1, 60, and 120, was shown to significantly improve ocular inflammation with preservation of best-corrected visual acuity in patients with noninfectious uveitis of the posterior segment, a phase III study has shown.
In the multinational SAKURA (Study Assessing Double-masked Uveitis Treatment) study, 346 study eyes were analyzed in this randomly assigned, double-masked, actively controlled study. In the study arm given intravitreal sirolimus 440 mcg, 22.8% (P = .025) met the primary endpoint of no vitreous haze (VH) at month 5 in the study eye without the aid of rescue therapy. In the group given intravitreal sirolimus 880 mcg, 16.4% (P = .182) met the primary endpoint, compared with 10.3% of active controls who were given 44 mcg intravitreal sirolimus.
For the secondary outcome, 52.6% (P = .008) of the intravitreal sirolimus 440 mcg arm had VH scores of 0 or a 0.5+ response rate at month 5. In the intravitreal sirolimus 880 mcg, 43.1% (P = .228) achieved a VH score of 0 or a 0.5+ response rate, compared with 35% of the 44 mcg active control group. Mean best-corrected visual acuity was maintained throughout the study in each study arm, with 76.9% of those who received corticosteroids at baseline in the 440 mcg study arm successfully tapering them to 5 mg per day or less by month 5, and 66.7% of those receiving corticosteroids in the 880 mcg group doing so. This was in comparison with 63.6% of those using corticosteroids in the active control group. Adverse events were similar across the study, and all doses were well tolerated. The study was funded by Santen.
Read the full study in Ophthalmology (2016;23[11]:2413-23).
[email protected]
On Twitter @whitneymcknight
Intravitreal sirolimus 440 mcg or 880 mcg administered on days 1, 60, and 120, was shown to significantly improve ocular inflammation with preservation of best-corrected visual acuity in patients with noninfectious uveitis of the posterior segment, a phase III study has shown.
In the multinational SAKURA (Study Assessing Double-masked Uveitis Treatment) study, 346 study eyes were analyzed in this randomly assigned, double-masked, actively controlled study. In the study arm given intravitreal sirolimus 440 mcg, 22.8% (P = .025) met the primary endpoint of no vitreous haze (VH) at month 5 in the study eye without the aid of rescue therapy. In the group given intravitreal sirolimus 880 mcg, 16.4% (P = .182) met the primary endpoint, compared with 10.3% of active controls who were given 44 mcg intravitreal sirolimus.
For the secondary outcome, 52.6% (P = .008) of the intravitreal sirolimus 440 mcg arm had VH scores of 0 or a 0.5+ response rate at month 5. In the intravitreal sirolimus 880 mcg, 43.1% (P = .228) achieved a VH score of 0 or a 0.5+ response rate, compared with 35% of the 44 mcg active control group. Mean best-corrected visual acuity was maintained throughout the study in each study arm, with 76.9% of those who received corticosteroids at baseline in the 440 mcg study arm successfully tapering them to 5 mg per day or less by month 5, and 66.7% of those receiving corticosteroids in the 880 mcg group doing so. This was in comparison with 63.6% of those using corticosteroids in the active control group. Adverse events were similar across the study, and all doses were well tolerated. The study was funded by Santen.
Read the full study in Ophthalmology (2016;23[11]:2413-23).
[email protected]
On Twitter @whitneymcknight
Amyloid PET scans may have clinical utility in patients with cognitive impairment
Amyloid PET scans can affect diagnostic thinking and patient management when used alongside routine diagnostic work up in adults suspected of having Alzheimer’s disease, results from the multicenter, open-label Assessment of the Incremental Diagnostic Value of Florbetapir 18F Imaging in Patients with Cognitive Impairment (INDIA-FBP) study reveal.
The investigators, led by Marina Boccardi, PhD, of the LANVIE-Laboratory of Neuroimaging of Aging at the University of Geneva, conducted the study to provide evidence of whether amyloid PET imaging has diagnostic utility in patients suspected of having Alzheimer’s disease because amyloid PET scanning in its current state has debatable clinical value because of a lack of disease-modifying drugs available to treat Alzheimer’s and the expense of the scans.
The trial was published in this week’s edition of JAMA Neurology and Dr. Boccardi and her colleagues found that amyloid PET scans in 228 cognitively impaired Italian adults improved diagnostic confidence and led to a change in diagnosis in 28% of patients whose prescan diagnosis was Alzheimer’s disease and in 25% (P = .02) of patients who had a non–Alzheimer’s disease–related dementia diagnosis. A positive scan resulted in a change in diagnosis to Alzheimer’s disease 72% of the time in patients with a prescan diagnosis of frontotemporal lobar degeneration (FTLD). Cognition-specific medications were initiated in 66% of previously untreated patients and were withdrawn in 33% of previously treated patients, results from the study showed (JAMA Neurol. 2016 Oct 31. doi: 10.1001/jamaneurol.2016.3751).
The scans’ ability to provide additional information to change a diagnosis justifies their use, especially when considering “reports of adverse events in patients with FTLD treated with cholinesterase inhibitors and of ineffectiveness for cognitive impairment of vascular etiology,” the investigators wrote.
The use of amyloid PET scans to change a diagnosis to Alzheimer’s disease or confirm its diagnosis also allowed for earlier detection and intervention, gave patients an opportunity to be included in clinical trials, and allowed patients to make residential and financial arrangements at a time when they were still able to express their preference.
Anticipated results from the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) and Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) studies will expand on the current observations on a larger scale as well as help to quantify the cost-effectiveness of amyloid PET in clinical routine practice, they said.
In the current study, a prescan diagnosis was made by clinicians who, at the time of the work-up, estimated diagnostic confidence and provided drug treatment. At the same time, an amyloid PET/CT scan was performed and the result was communicated to the clinicians upon work-up completion. Clinicians relied on the scan results for their final clinical diagnoses and identification of the most-appropriate treatment.
Amyloid PET scans are currently not reimbursed by the Centers for Medicare & Medicaid Services outside of their use in clinical trials.
This study was sponsored by Istituto di Ricovero e Cura a Carattere Scientifico Centro San Giovanni di Dio Fatebenefratelli in Brescia, Italy, and Avid Radiopharmaceuticals. Several of the authors reported serving on the scientific advisory boards of pharmaceutical companies.
While amyloid PET scans have a clear role in research and in the right clinical setting they can support a suspected diagnosis of Alzheimer’s disease or help a clinician to choose between Alzheimer’s and a non-Alzheimer’s condition, their use can have pitfalls even at a diagnostically simplified level.
There are at least four patient populations in whom amyloid PET scans could potentially have clinical utility, but these are not addressed in the current debate over their use or in this study: patients with early-onset dementia, patients with normal pressure hydrocephalus, patients with rapidly progressive dementia in which the differential diagnosis includes some reversible conditions that may require a diagnostic brain biopsy, and rare patients with cerebral amyloid angiopathy who develop tumorlike accumulations that necessitate a brain biopsy for diagnosis.
Richard J. Caselli, MD, and Bryan K. Woodruff, MD, are with the department of neurology at the Mayo Clinic Arizona, Scottsdale. Their comments are derived from an editorial accompanying Dr. Boccardi and colleagues’ report (JAMA Neurol. 2016 Oct 31. doi: 10.1001/jamaneurol.2016.3792). Dr. Caselli reported receiving research funding from Merck, and Dr. Woodruff reported receiving research funding from Genentech and Avid Pharmaceuticals.
While amyloid PET scans have a clear role in research and in the right clinical setting they can support a suspected diagnosis of Alzheimer’s disease or help a clinician to choose between Alzheimer’s and a non-Alzheimer’s condition, their use can have pitfalls even at a diagnostically simplified level.
There are at least four patient populations in whom amyloid PET scans could potentially have clinical utility, but these are not addressed in the current debate over their use or in this study: patients with early-onset dementia, patients with normal pressure hydrocephalus, patients with rapidly progressive dementia in which the differential diagnosis includes some reversible conditions that may require a diagnostic brain biopsy, and rare patients with cerebral amyloid angiopathy who develop tumorlike accumulations that necessitate a brain biopsy for diagnosis.
Richard J. Caselli, MD, and Bryan K. Woodruff, MD, are with the department of neurology at the Mayo Clinic Arizona, Scottsdale. Their comments are derived from an editorial accompanying Dr. Boccardi and colleagues’ report (JAMA Neurol. 2016 Oct 31. doi: 10.1001/jamaneurol.2016.3792). Dr. Caselli reported receiving research funding from Merck, and Dr. Woodruff reported receiving research funding from Genentech and Avid Pharmaceuticals.
While amyloid PET scans have a clear role in research and in the right clinical setting they can support a suspected diagnosis of Alzheimer’s disease or help a clinician to choose between Alzheimer’s and a non-Alzheimer’s condition, their use can have pitfalls even at a diagnostically simplified level.
There are at least four patient populations in whom amyloid PET scans could potentially have clinical utility, but these are not addressed in the current debate over their use or in this study: patients with early-onset dementia, patients with normal pressure hydrocephalus, patients with rapidly progressive dementia in which the differential diagnosis includes some reversible conditions that may require a diagnostic brain biopsy, and rare patients with cerebral amyloid angiopathy who develop tumorlike accumulations that necessitate a brain biopsy for diagnosis.
Richard J. Caselli, MD, and Bryan K. Woodruff, MD, are with the department of neurology at the Mayo Clinic Arizona, Scottsdale. Their comments are derived from an editorial accompanying Dr. Boccardi and colleagues’ report (JAMA Neurol. 2016 Oct 31. doi: 10.1001/jamaneurol.2016.3792). Dr. Caselli reported receiving research funding from Merck, and Dr. Woodruff reported receiving research funding from Genentech and Avid Pharmaceuticals.
Amyloid PET scans can affect diagnostic thinking and patient management when used alongside routine diagnostic work up in adults suspected of having Alzheimer’s disease, results from the multicenter, open-label Assessment of the Incremental Diagnostic Value of Florbetapir 18F Imaging in Patients with Cognitive Impairment (INDIA-FBP) study reveal.
The investigators, led by Marina Boccardi, PhD, of the LANVIE-Laboratory of Neuroimaging of Aging at the University of Geneva, conducted the study to provide evidence of whether amyloid PET imaging has diagnostic utility in patients suspected of having Alzheimer’s disease because amyloid PET scanning in its current state has debatable clinical value because of a lack of disease-modifying drugs available to treat Alzheimer’s and the expense of the scans.
The trial was published in this week’s edition of JAMA Neurology and Dr. Boccardi and her colleagues found that amyloid PET scans in 228 cognitively impaired Italian adults improved diagnostic confidence and led to a change in diagnosis in 28% of patients whose prescan diagnosis was Alzheimer’s disease and in 25% (P = .02) of patients who had a non–Alzheimer’s disease–related dementia diagnosis. A positive scan resulted in a change in diagnosis to Alzheimer’s disease 72% of the time in patients with a prescan diagnosis of frontotemporal lobar degeneration (FTLD). Cognition-specific medications were initiated in 66% of previously untreated patients and were withdrawn in 33% of previously treated patients, results from the study showed (JAMA Neurol. 2016 Oct 31. doi: 10.1001/jamaneurol.2016.3751).
The scans’ ability to provide additional information to change a diagnosis justifies their use, especially when considering “reports of adverse events in patients with FTLD treated with cholinesterase inhibitors and of ineffectiveness for cognitive impairment of vascular etiology,” the investigators wrote.
The use of amyloid PET scans to change a diagnosis to Alzheimer’s disease or confirm its diagnosis also allowed for earlier detection and intervention, gave patients an opportunity to be included in clinical trials, and allowed patients to make residential and financial arrangements at a time when they were still able to express their preference.
Anticipated results from the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) and Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) studies will expand on the current observations on a larger scale as well as help to quantify the cost-effectiveness of amyloid PET in clinical routine practice, they said.
In the current study, a prescan diagnosis was made by clinicians who, at the time of the work-up, estimated diagnostic confidence and provided drug treatment. At the same time, an amyloid PET/CT scan was performed and the result was communicated to the clinicians upon work-up completion. Clinicians relied on the scan results for their final clinical diagnoses and identification of the most-appropriate treatment.
Amyloid PET scans are currently not reimbursed by the Centers for Medicare & Medicaid Services outside of their use in clinical trials.
This study was sponsored by Istituto di Ricovero e Cura a Carattere Scientifico Centro San Giovanni di Dio Fatebenefratelli in Brescia, Italy, and Avid Radiopharmaceuticals. Several of the authors reported serving on the scientific advisory boards of pharmaceutical companies.
Amyloid PET scans can affect diagnostic thinking and patient management when used alongside routine diagnostic work up in adults suspected of having Alzheimer’s disease, results from the multicenter, open-label Assessment of the Incremental Diagnostic Value of Florbetapir 18F Imaging in Patients with Cognitive Impairment (INDIA-FBP) study reveal.
The investigators, led by Marina Boccardi, PhD, of the LANVIE-Laboratory of Neuroimaging of Aging at the University of Geneva, conducted the study to provide evidence of whether amyloid PET imaging has diagnostic utility in patients suspected of having Alzheimer’s disease because amyloid PET scanning in its current state has debatable clinical value because of a lack of disease-modifying drugs available to treat Alzheimer’s and the expense of the scans.
The trial was published in this week’s edition of JAMA Neurology and Dr. Boccardi and her colleagues found that amyloid PET scans in 228 cognitively impaired Italian adults improved diagnostic confidence and led to a change in diagnosis in 28% of patients whose prescan diagnosis was Alzheimer’s disease and in 25% (P = .02) of patients who had a non–Alzheimer’s disease–related dementia diagnosis. A positive scan resulted in a change in diagnosis to Alzheimer’s disease 72% of the time in patients with a prescan diagnosis of frontotemporal lobar degeneration (FTLD). Cognition-specific medications were initiated in 66% of previously untreated patients and were withdrawn in 33% of previously treated patients, results from the study showed (JAMA Neurol. 2016 Oct 31. doi: 10.1001/jamaneurol.2016.3751).
The scans’ ability to provide additional information to change a diagnosis justifies their use, especially when considering “reports of adverse events in patients with FTLD treated with cholinesterase inhibitors and of ineffectiveness for cognitive impairment of vascular etiology,” the investigators wrote.
The use of amyloid PET scans to change a diagnosis to Alzheimer’s disease or confirm its diagnosis also allowed for earlier detection and intervention, gave patients an opportunity to be included in clinical trials, and allowed patients to make residential and financial arrangements at a time when they were still able to express their preference.
Anticipated results from the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) and Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) studies will expand on the current observations on a larger scale as well as help to quantify the cost-effectiveness of amyloid PET in clinical routine practice, they said.
In the current study, a prescan diagnosis was made by clinicians who, at the time of the work-up, estimated diagnostic confidence and provided drug treatment. At the same time, an amyloid PET/CT scan was performed and the result was communicated to the clinicians upon work-up completion. Clinicians relied on the scan results for their final clinical diagnoses and identification of the most-appropriate treatment.
Amyloid PET scans are currently not reimbursed by the Centers for Medicare & Medicaid Services outside of their use in clinical trials.
This study was sponsored by Istituto di Ricovero e Cura a Carattere Scientifico Centro San Giovanni di Dio Fatebenefratelli in Brescia, Italy, and Avid Radiopharmaceuticals. Several of the authors reported serving on the scientific advisory boards of pharmaceutical companies.
Key clinical point:
Main finding: Amyloid PET scans led to a change in diagnosis in 28% of patients whose prescan diagnosis was Alzheimer’s disease (AD) and in 25% of patients who had a non–AD related dementia diagnosis.
Source: Multicenter, open-label study of the incremental diagnostic value of Florbetapir 18F imaging in 228 adult patients with cognitive impairment.
Disclosures: This study was sponsored by Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro San Giovanni di Dio Fatebenefratelli in Brescia, Italy, and Avid Radiopharmaceuticals. Several of the authors reported serving on the scientific advisory boards of pharmaceutical companies.
Drug enhances carboplatin efficacy against ovarian cancer
The WEE1 tyrosine kinase inhibitor AZD1775 enhanced carboplatin’s antitumor activity in a phase II proof-of-concept trial of refractory or resistant TP53-mediated ovarian cancer, according to a report in the Journal of Clinical Oncology.
The manufacturer-sponsored open-label nonrandomized trial involved 23 women (median age, 58 years; range, 25-74 years) who had epithelial ovarian cancer and TP53 mutations and whose disease didn’t respond to or recurred after first-line platinum plus paclitaxel therapy. All the participants also underwent either primary or interval debulking surgery, said Suzanne Leijen, MD, PhD, of The Netherlands Cancer Institute, Amsterdam, and her associates.
The patients took 225 mg AZD1775 orally twice a day for 3 days along with IV carboplatin in 21-day cycles, until the cancer progressed. The primary outcome measure, overall response rate, was 43% in the 21 evaluable patients. After two treatment cycles, one patient had a complete response, eight had a partial response, seven had stable disease, and five had progressive disease.
“This response rate exceeds the effect that could be expected with second-line single-agent treatment options, including paclitaxel, pegylated liposomal doxorubicin, bevacizumab, and topotecan, which have reported response rates of 11%-21%,” the investigators said (J Clin Oncol. 2016 Oct. 31. doi: 10.1200/JCO.2016.67.5942).
The median progression-free survival was 5.3 months and median overall survival was 12.6 months. One patient showed a partial response for 31 months and another showed a complete response for 42 months, and both continue to receive the treatment.
AZD1775 plus carboplatin “was generally well tolerated and demonstrated manageable toxicity,” including nausea, vomiting, diarrhea, fatigue, bone marrow suppression, thrombocytopenia, and neutropenia.
This study was supported by Merck, which was involved in the data analysis and interpretation. Dr. Leijen reported having no relevant financial disclosures; her associates reported ties to Merck, AstraZeneca, Roche, Novartis, Advaxis, and Modra Pharmaceuticals.
The WEE1 tyrosine kinase inhibitor AZD1775 enhanced carboplatin’s antitumor activity in a phase II proof-of-concept trial of refractory or resistant TP53-mediated ovarian cancer, according to a report in the Journal of Clinical Oncology.
The manufacturer-sponsored open-label nonrandomized trial involved 23 women (median age, 58 years; range, 25-74 years) who had epithelial ovarian cancer and TP53 mutations and whose disease didn’t respond to or recurred after first-line platinum plus paclitaxel therapy. All the participants also underwent either primary or interval debulking surgery, said Suzanne Leijen, MD, PhD, of The Netherlands Cancer Institute, Amsterdam, and her associates.
The patients took 225 mg AZD1775 orally twice a day for 3 days along with IV carboplatin in 21-day cycles, until the cancer progressed. The primary outcome measure, overall response rate, was 43% in the 21 evaluable patients. After two treatment cycles, one patient had a complete response, eight had a partial response, seven had stable disease, and five had progressive disease.
“This response rate exceeds the effect that could be expected with second-line single-agent treatment options, including paclitaxel, pegylated liposomal doxorubicin, bevacizumab, and topotecan, which have reported response rates of 11%-21%,” the investigators said (J Clin Oncol. 2016 Oct. 31. doi: 10.1200/JCO.2016.67.5942).
The median progression-free survival was 5.3 months and median overall survival was 12.6 months. One patient showed a partial response for 31 months and another showed a complete response for 42 months, and both continue to receive the treatment.
AZD1775 plus carboplatin “was generally well tolerated and demonstrated manageable toxicity,” including nausea, vomiting, diarrhea, fatigue, bone marrow suppression, thrombocytopenia, and neutropenia.
This study was supported by Merck, which was involved in the data analysis and interpretation. Dr. Leijen reported having no relevant financial disclosures; her associates reported ties to Merck, AstraZeneca, Roche, Novartis, Advaxis, and Modra Pharmaceuticals.
The WEE1 tyrosine kinase inhibitor AZD1775 enhanced carboplatin’s antitumor activity in a phase II proof-of-concept trial of refractory or resistant TP53-mediated ovarian cancer, according to a report in the Journal of Clinical Oncology.
The manufacturer-sponsored open-label nonrandomized trial involved 23 women (median age, 58 years; range, 25-74 years) who had epithelial ovarian cancer and TP53 mutations and whose disease didn’t respond to or recurred after first-line platinum plus paclitaxel therapy. All the participants also underwent either primary or interval debulking surgery, said Suzanne Leijen, MD, PhD, of The Netherlands Cancer Institute, Amsterdam, and her associates.
The patients took 225 mg AZD1775 orally twice a day for 3 days along with IV carboplatin in 21-day cycles, until the cancer progressed. The primary outcome measure, overall response rate, was 43% in the 21 evaluable patients. After two treatment cycles, one patient had a complete response, eight had a partial response, seven had stable disease, and five had progressive disease.
“This response rate exceeds the effect that could be expected with second-line single-agent treatment options, including paclitaxel, pegylated liposomal doxorubicin, bevacizumab, and topotecan, which have reported response rates of 11%-21%,” the investigators said (J Clin Oncol. 2016 Oct. 31. doi: 10.1200/JCO.2016.67.5942).
The median progression-free survival was 5.3 months and median overall survival was 12.6 months. One patient showed a partial response for 31 months and another showed a complete response for 42 months, and both continue to receive the treatment.
AZD1775 plus carboplatin “was generally well tolerated and demonstrated manageable toxicity,” including nausea, vomiting, diarrhea, fatigue, bone marrow suppression, thrombocytopenia, and neutropenia.
This study was supported by Merck, which was involved in the data analysis and interpretation. Dr. Leijen reported having no relevant financial disclosures; her associates reported ties to Merck, AstraZeneca, Roche, Novartis, Advaxis, and Modra Pharmaceuticals.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The WEE1 tyrosine kinase inhibitor AZD1775 enhanced carboplatin’s antitumor activity in refractory or resistant TP53-mutated ovarian cancer.
Major finding: The overall response rate was 43% in 21 evaluable patients: One patient had a complete response, eight had a partial response, seven had stable disease, and five had progressive disease.
Data source: A proof-of-concept open-label nonrandomized phase II study involving 23 patients.
Disclosures: This study was supported by Merck, which was involved in the data analysis and interpretation. Dr. Leijen reported having no relevant financial disclosures; her associates reported ties to Merck, AstraZeneca, Roche, Novartis, Advaxis, and Modra Pharmaceuticals.
Causes of recurrent pediatric pancreatitis start to emerge
MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.
This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.
The analysis focused on the 83 patients with at least 3 months of follow-up. During observation, 17 (20%) of the patients developed a second episode of acute pancreatitis that was distinguished from the initial episode by either at least 1 pain-free month or by complete normalization of amylase and lipase levels between the two episodes. Thirteen of the 17 recurrences occurred within 5 months of the first episode, with 11 of these occurring within the first 3 months after the first attack, a subgroup Dr. Sweeny called the “rapid progressors.”
Comparison of the 11 rapid progressors with the other 72 patients showed that the rapid progressors were significantly taller and weighed more. In addition, two of the 11 rapid progressors had pancreatic necrosis while none of the other patients had this complication.
The pancreatitis etiologies of the 11 rapid progressors also highlighted the potent influence a mutation can have on producing recurrent acute pancreatitis. Four of the 11 rapid progressors had a genetic mutation linked to pancreatitis susceptibility, and five of the six patients with a genetic cause for their index episode of pancreatitis developed a second acute episode during follow-up, said Dr. Sweeny, a pediatrician at Cincinnati Children’s Hospital Medical Center. In contrast, the next most effective cause of recurrent pancreatitis was a toxin or drug, which resulted in about a 25% incidence rate of a second episode. All of the other pancreatitis etiologies had recurrence rates of 10% or less.
Collecting better information on the causes of recurrent pancreatitis and chronic pancreatitis is especially important because of the rising incidence of acute pediatric pancreatitis, currently about one case in every 10,000 children and adolescents. Prior to formation of the INSPPIRE consortium, studies of pediatric pancreatitis had largely been limited to single-center retrospective reviews. The limitations of these data have made it hard to predict which patients with a first episode of acute pancreatitis will progress to a second episode or beyond, Dr. Sweeny said.
Dr. Sweeny had no disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.
This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.
The analysis focused on the 83 patients with at least 3 months of follow-up. During observation, 17 (20%) of the patients developed a second episode of acute pancreatitis that was distinguished from the initial episode by either at least 1 pain-free month or by complete normalization of amylase and lipase levels between the two episodes. Thirteen of the 17 recurrences occurred within 5 months of the first episode, with 11 of these occurring within the first 3 months after the first attack, a subgroup Dr. Sweeny called the “rapid progressors.”
Comparison of the 11 rapid progressors with the other 72 patients showed that the rapid progressors were significantly taller and weighed more. In addition, two of the 11 rapid progressors had pancreatic necrosis while none of the other patients had this complication.
The pancreatitis etiologies of the 11 rapid progressors also highlighted the potent influence a mutation can have on producing recurrent acute pancreatitis. Four of the 11 rapid progressors had a genetic mutation linked to pancreatitis susceptibility, and five of the six patients with a genetic cause for their index episode of pancreatitis developed a second acute episode during follow-up, said Dr. Sweeny, a pediatrician at Cincinnati Children’s Hospital Medical Center. In contrast, the next most effective cause of recurrent pancreatitis was a toxin or drug, which resulted in about a 25% incidence rate of a second episode. All of the other pancreatitis etiologies had recurrence rates of 10% or less.
Collecting better information on the causes of recurrent pancreatitis and chronic pancreatitis is especially important because of the rising incidence of acute pediatric pancreatitis, currently about one case in every 10,000 children and adolescents. Prior to formation of the INSPPIRE consortium, studies of pediatric pancreatitis had largely been limited to single-center retrospective reviews. The limitations of these data have made it hard to predict which patients with a first episode of acute pancreatitis will progress to a second episode or beyond, Dr. Sweeny said.
Dr. Sweeny had no disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.
This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.
The analysis focused on the 83 patients with at least 3 months of follow-up. During observation, 17 (20%) of the patients developed a second episode of acute pancreatitis that was distinguished from the initial episode by either at least 1 pain-free month or by complete normalization of amylase and lipase levels between the two episodes. Thirteen of the 17 recurrences occurred within 5 months of the first episode, with 11 of these occurring within the first 3 months after the first attack, a subgroup Dr. Sweeny called the “rapid progressors.”
Comparison of the 11 rapid progressors with the other 72 patients showed that the rapid progressors were significantly taller and weighed more. In addition, two of the 11 rapid progressors had pancreatic necrosis while none of the other patients had this complication.
The pancreatitis etiologies of the 11 rapid progressors also highlighted the potent influence a mutation can have on producing recurrent acute pancreatitis. Four of the 11 rapid progressors had a genetic mutation linked to pancreatitis susceptibility, and five of the six patients with a genetic cause for their index episode of pancreatitis developed a second acute episode during follow-up, said Dr. Sweeny, a pediatrician at Cincinnati Children’s Hospital Medical Center. In contrast, the next most effective cause of recurrent pancreatitis was a toxin or drug, which resulted in about a 25% incidence rate of a second episode. All of the other pancreatitis etiologies had recurrence rates of 10% or less.
Collecting better information on the causes of recurrent pancreatitis and chronic pancreatitis is especially important because of the rising incidence of acute pediatric pancreatitis, currently about one case in every 10,000 children and adolescents. Prior to formation of the INSPPIRE consortium, studies of pediatric pancreatitis had largely been limited to single-center retrospective reviews. The limitations of these data have made it hard to predict which patients with a first episode of acute pancreatitis will progress to a second episode or beyond, Dr. Sweeny said.
Dr. Sweeny had no disclosures.
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point:
Major finding: Overall, 17 of 83 patients (20%) had recurrent acute pancreatitis, but among six patients with a genetic cause, five had recurrences.
Data source: Eighty-three patients enrolled in INSPPIRE, an international consortium formed to prospectively study pediatric pancreatitis.
Disclosures: Dr. Sweeny had no disclosures.
Statins Are Underused in Recent-Onset Parkinson’s Disease
Many patients with recent-onset Parkinson’s disease have increased cardiovascular risk, but statin therapy is underused in this population, according to research published online ahead of print September 26 in the Journal of Neurology, Neurosurgery and Psychiatry. Increased cardiovascular risk is associated with greater motor and cognitive severity and greater axial impairment. Increased use of statins may reduce chronic vascular damage, and thereby slow the progression of motor and cognitive decline in this population, said the authors.
Cardiovascular disease influences phenotypic variation in Parkinson’s disease, but data are unclear about whether cardiovascular risk factors influence Parkinson’s disease phenotype, said Diane M. A. Swallow, MB, ChB, a clinical research fellow in movement disorders at Queen Elizabeth University Hospital in Glasgow. She and her colleagues studied prospectively enrolled participants in the UK Tracking Parkinson’s study and the Oxford Discovery study to quantify vascular risk and statin use in patients with recent-onset Parkinson’s disease. The investigators also sought to clarify the relationship between vascular risk and the severity and phenotype of Parkinson’s disease.
Cardiovascular risk was quantified using the QRISK2-2015 prediction algorithm, which computes risk based on traditional risk factors (eg, age, systolic blood pressure, smoking status, and ratio of total serum cholesterol to high-density lipoprotein cholesterol) together with BMI, ethnicity, measures of deprivation, family history, chronic kidney disease, rheumatoid arthritis, atrial fibrillation, diabetes mellitus, and antihypertensive treatment.
In all, 2,909 patients were analyzed. The population’s mean age was 67.5, mean disease duration was 1.3 years, and 65.3% of the sample was male. As calculated by the QRISK2-2015, 10-year cardiovascular risk was low for 22.3%, medium for 28.7%, and high for 33.8% of the sample, respectively. Statins were prescribed in 15.1% of patients with medium vascular risk and in 37.2% of patients with high vascular risk. In contrast, statins were prescribed in 75.3% of participants with established vascular disease.
Increasing vascular risk was associated with worsening scores on Part 3 of the Unified Parkinson’s Disease Rating Scale when adjusted for age, sex, disease duration, and coffee consumption. Increasing vascular risk was also associated with increasing cognitive impairment, a worsening score on the Montreal Cognitive Assessment (MoCA), and an increasing proportion of patients with mild cognitive impairment and dementia. The motor and cognitive characteristics of participants with high vascular risk were similar to those of participants with established vascular disease.
Among individuals with established vascular disease and a QRISK2 score of 10% or greater, people who were treated with statins were less likely to have the postural instability and gait difficulty subtype of Parkinson’s disease, but had lower total MoCA scores and were more likely to have cognitive impairment. Among patients with established cardiovascular disease, people treated with statins had better cognition, but did not significantly differ in their likelihood of having postural instability and gait difficulty.
“In assessing our findings, we need to consider that the patients are likely to have been recommended for statins based on their clinical findings, so we cannot compare these groups as if they had been randomized to statin therapy. It is clear that increased vascular risk adds to the burden of gait and cognitive impairment that we see in patients with Parkinson’s disease, and that this [risk] is undertreated,” said Dr. Swallow.
—Erik Greb
Suggested Reading
Swallow DM, Lawton MA, Grosset KA, et al. Statins are underused in recent-onset Parkinson’s disease with increased vascular risk: findings from the UK Tracking Parkinson’s and Oxford Parkinson’s Disease Centre (OPDC) discovery cohorts. J Neurol Neurosurg Psychiatry. 2016 Sep 26 [Epub ahead of print].
Many patients with recent-onset Parkinson’s disease have increased cardiovascular risk, but statin therapy is underused in this population, according to research published online ahead of print September 26 in the Journal of Neurology, Neurosurgery and Psychiatry. Increased cardiovascular risk is associated with greater motor and cognitive severity and greater axial impairment. Increased use of statins may reduce chronic vascular damage, and thereby slow the progression of motor and cognitive decline in this population, said the authors.
Cardiovascular disease influences phenotypic variation in Parkinson’s disease, but data are unclear about whether cardiovascular risk factors influence Parkinson’s disease phenotype, said Diane M. A. Swallow, MB, ChB, a clinical research fellow in movement disorders at Queen Elizabeth University Hospital in Glasgow. She and her colleagues studied prospectively enrolled participants in the UK Tracking Parkinson’s study and the Oxford Discovery study to quantify vascular risk and statin use in patients with recent-onset Parkinson’s disease. The investigators also sought to clarify the relationship between vascular risk and the severity and phenotype of Parkinson’s disease.
Cardiovascular risk was quantified using the QRISK2-2015 prediction algorithm, which computes risk based on traditional risk factors (eg, age, systolic blood pressure, smoking status, and ratio of total serum cholesterol to high-density lipoprotein cholesterol) together with BMI, ethnicity, measures of deprivation, family history, chronic kidney disease, rheumatoid arthritis, atrial fibrillation, diabetes mellitus, and antihypertensive treatment.
In all, 2,909 patients were analyzed. The population’s mean age was 67.5, mean disease duration was 1.3 years, and 65.3% of the sample was male. As calculated by the QRISK2-2015, 10-year cardiovascular risk was low for 22.3%, medium for 28.7%, and high for 33.8% of the sample, respectively. Statins were prescribed in 15.1% of patients with medium vascular risk and in 37.2% of patients with high vascular risk. In contrast, statins were prescribed in 75.3% of participants with established vascular disease.
Increasing vascular risk was associated with worsening scores on Part 3 of the Unified Parkinson’s Disease Rating Scale when adjusted for age, sex, disease duration, and coffee consumption. Increasing vascular risk was also associated with increasing cognitive impairment, a worsening score on the Montreal Cognitive Assessment (MoCA), and an increasing proportion of patients with mild cognitive impairment and dementia. The motor and cognitive characteristics of participants with high vascular risk were similar to those of participants with established vascular disease.
Among individuals with established vascular disease and a QRISK2 score of 10% or greater, people who were treated with statins were less likely to have the postural instability and gait difficulty subtype of Parkinson’s disease, but had lower total MoCA scores and were more likely to have cognitive impairment. Among patients with established cardiovascular disease, people treated with statins had better cognition, but did not significantly differ in their likelihood of having postural instability and gait difficulty.
“In assessing our findings, we need to consider that the patients are likely to have been recommended for statins based on their clinical findings, so we cannot compare these groups as if they had been randomized to statin therapy. It is clear that increased vascular risk adds to the burden of gait and cognitive impairment that we see in patients with Parkinson’s disease, and that this [risk] is undertreated,” said Dr. Swallow.
—Erik Greb
Suggested Reading
Swallow DM, Lawton MA, Grosset KA, et al. Statins are underused in recent-onset Parkinson’s disease with increased vascular risk: findings from the UK Tracking Parkinson’s and Oxford Parkinson’s Disease Centre (OPDC) discovery cohorts. J Neurol Neurosurg Psychiatry. 2016 Sep 26 [Epub ahead of print].
Many patients with recent-onset Parkinson’s disease have increased cardiovascular risk, but statin therapy is underused in this population, according to research published online ahead of print September 26 in the Journal of Neurology, Neurosurgery and Psychiatry. Increased cardiovascular risk is associated with greater motor and cognitive severity and greater axial impairment. Increased use of statins may reduce chronic vascular damage, and thereby slow the progression of motor and cognitive decline in this population, said the authors.
Cardiovascular disease influences phenotypic variation in Parkinson’s disease, but data are unclear about whether cardiovascular risk factors influence Parkinson’s disease phenotype, said Diane M. A. Swallow, MB, ChB, a clinical research fellow in movement disorders at Queen Elizabeth University Hospital in Glasgow. She and her colleagues studied prospectively enrolled participants in the UK Tracking Parkinson’s study and the Oxford Discovery study to quantify vascular risk and statin use in patients with recent-onset Parkinson’s disease. The investigators also sought to clarify the relationship between vascular risk and the severity and phenotype of Parkinson’s disease.
Cardiovascular risk was quantified using the QRISK2-2015 prediction algorithm, which computes risk based on traditional risk factors (eg, age, systolic blood pressure, smoking status, and ratio of total serum cholesterol to high-density lipoprotein cholesterol) together with BMI, ethnicity, measures of deprivation, family history, chronic kidney disease, rheumatoid arthritis, atrial fibrillation, diabetes mellitus, and antihypertensive treatment.
In all, 2,909 patients were analyzed. The population’s mean age was 67.5, mean disease duration was 1.3 years, and 65.3% of the sample was male. As calculated by the QRISK2-2015, 10-year cardiovascular risk was low for 22.3%, medium for 28.7%, and high for 33.8% of the sample, respectively. Statins were prescribed in 15.1% of patients with medium vascular risk and in 37.2% of patients with high vascular risk. In contrast, statins were prescribed in 75.3% of participants with established vascular disease.
Increasing vascular risk was associated with worsening scores on Part 3 of the Unified Parkinson’s Disease Rating Scale when adjusted for age, sex, disease duration, and coffee consumption. Increasing vascular risk was also associated with increasing cognitive impairment, a worsening score on the Montreal Cognitive Assessment (MoCA), and an increasing proportion of patients with mild cognitive impairment and dementia. The motor and cognitive characteristics of participants with high vascular risk were similar to those of participants with established vascular disease.
Among individuals with established vascular disease and a QRISK2 score of 10% or greater, people who were treated with statins were less likely to have the postural instability and gait difficulty subtype of Parkinson’s disease, but had lower total MoCA scores and were more likely to have cognitive impairment. Among patients with established cardiovascular disease, people treated with statins had better cognition, but did not significantly differ in their likelihood of having postural instability and gait difficulty.
“In assessing our findings, we need to consider that the patients are likely to have been recommended for statins based on their clinical findings, so we cannot compare these groups as if they had been randomized to statin therapy. It is clear that increased vascular risk adds to the burden of gait and cognitive impairment that we see in patients with Parkinson’s disease, and that this [risk] is undertreated,” said Dr. Swallow.
—Erik Greb
Suggested Reading
Swallow DM, Lawton MA, Grosset KA, et al. Statins are underused in recent-onset Parkinson’s disease with increased vascular risk: findings from the UK Tracking Parkinson’s and Oxford Parkinson’s Disease Centre (OPDC) discovery cohorts. J Neurol Neurosurg Psychiatry. 2016 Sep 26 [Epub ahead of print].
How Much MS Disease Activity Is Acceptable?
LONDON—No evidence of disease activity (NEDA) is a worthy but potentially problematic goal in the care of patients with multiple sclerosis (MS), according to an overview provided at the 32nd Congress of the European Committee for Treatment and Research in MS. The definition of NEDA is evolving as neurologists adopt new metrics in clinical practice, and NEDA is a difficult outcome to sustain in the long term.
Studies of interferon beta suggest that a minimal amount of clinical or MRI activity is not necessarily associated with poor long-term outcomes. Such research raises the possibility that minimal evidence of disease activity (MEDA) could be an appropriate goal of treatment, said Mar Tintoré, MD, PhD, neurologist at the MS Centre of Catalonia in Barcelona. 
The Emergence of NEDA
A patient receiving treatment who has no sustained disability progression, no relapses, and no new T2 or gadolinium-enhancing lesions has NEDA, as the term was originally conceived. The outcome was rapidly adopted in clinical trials. NEDA also has been applied in the clinical setting. In one study of patients with MS treated in clinical practice, 54% had NEDA at one year. Researchers also found that NEDA may predict long-term outcomes. In one study, 78% of patients with NEDA at year two did not have disease progression at year seven.
A drawback of NEDA is that disease activity may be diffuse and may not manifest itself in relapses, new lesions, or disability progression. “It also may give a false sense of security to the doctor and to the patient,” said Dr. Tintoré.
A fourth factor, brain volume loss, recently was incorporated into NEDA, which has come to be called NEDA-4. Two studies have determined that a 0.4% annual rate of brain volume loss is the best threshold for distinguishing between people with MS and healthy controls.
The Difficulties of NEDA
The new conception of NEDA still omits several factors that neurologists may consider important. NEDA does not take cognition into account, but adding the MS Functional Composite to the NEDA criteria could change that. Patient-reported outcomes such as fatigue, depression, and quality of life also might be appropriate outcomes to incorporate into NEDA, said Dr. Tintoré. In addition, biomarkers such as CSF levels of neurofilament light indicate treatment response and could be added to NEDA.
Current clinical practice may make it difficult to assess whether a patient has NEDA. Many neurologists perform an MRI on a patient before initiating treatment and again at 12 months. “Many of the drugs that we are currently using are not active from baseline,” said Dr. Tintoré. Because changes in the first six months of treatment do not necessarily indicate treatment response, it may be necessary to perform another MRI after several months of treatment as a second baseline measurement, said Dr. Tintoré.
Furthermore, agreement between neuroradiologists is not high. Researchers have observed great variability between readers who had been asked to assess the presence of new T2 or gadolinium-enhancing lesions. And although standardized MRI protocols have been established, they may not be followed uniformly, perhaps because of difficulties specific to given facilities.
Is MEDA an Appropriate Goal?
One potential argument in favor of adopting NEDA as a goal of treatment is that disease activity often predicts poor long-term outcomes. Dr. Tintoré and colleagues assessed the treatment effect in patients with relapsing-remitting MS after two years of interferon therapy. They followed patients for 12 years. Clinical activity during the first two years of treatment was associated with increased risks of developing secondary progressive MS, of reaching an Expanded Disability Status Scale (EDSS) score of 7, and of having a five-point increase on the EDSS at 12 years.
Yet patients with little disease activity may still have good long-term outcomes. In a separate study, Dr. Tintoré and colleagues assessed the presence of MRI lesions after one year in patients with relapsing-remitting MS who were receiving interferon treatment. Participants were followed for eight years, and the primary end point was an increase of at least two points on EDSS after eight years. The investigators found no difference in outcome at eight years between patients who had one gadolinium-enhancing lesion at one year and those who had none at one year. Patients who had two or more gadolinium-enhancing lesions at one year, however, were more likely to reach the primary end point than patients who had fewer than two gadolinium-enhancing lesions at one year.
Results were similar for new T2 lesions. There was no difference in outcome at eight years between participants with no new T2 lesions at one year and those with one or two new T2 lesions at one year. Patients with three or more new T2 lesions at one year, however, were more likely to reach the primary end point. The Rio score was able to predict which patients would have more disability progression, but NEDA was not able to do so, said Dr. Tintoré. These results are similar to those of the MRI in MS (MAGNIMS) data set, in which a low level of disease activity was not associated with poor long-term outcome.
“Combined clinical and MRI scores allow us to integrate disease activity data into individual therapeutic decisions for our patients with MS,” said Dr. Tintoré. Newer therapies have made NEDA attainable for more patients, but not for all patients. Because minimal clinical or MRI activity is not necessarily associated with a poor response in the long term, neurologists may debate whether or when MEDA is an acceptable goal of treatment.
—Erik Greb
Suggested Reading
Giovannoni G, Turner B, Gnanapavan S, et al. Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult Scler Relat Disord. 2015;4(4):329-333.
Kappos L, De Stefano N, Freedman MS, et al. Inclusion of brain volume loss in a revised measure of ‘no evidence of disease activity’ (NEDA-4) in relapsing-remitting multiple sclerosis. Mult Scler. 2016;22(10):1297-1305.
Río J, Castilló J, Rovira A, et al. Measures in the first year of therapy predict the response to interferon beta in MS. Mult Scler. 2009;15(7):848-853.
Uher T, Havrdova E, Sobisek L, et al. Is no evidence of disease activity an achievable goal in MS patients on intramuscular interferon beta-1a treatment over long-term follow-up? Mult Scler. 2016 May 26 [Epub ahead of print].
LONDON—No evidence of disease activity (NEDA) is a worthy but potentially problematic goal in the care of patients with multiple sclerosis (MS), according to an overview provided at the 32nd Congress of the European Committee for Treatment and Research in MS. The definition of NEDA is evolving as neurologists adopt new metrics in clinical practice, and NEDA is a difficult outcome to sustain in the long term.
Studies of interferon beta suggest that a minimal amount of clinical or MRI activity is not necessarily associated with poor long-term outcomes. Such research raises the possibility that minimal evidence of disease activity (MEDA) could be an appropriate goal of treatment, said Mar Tintoré, MD, PhD, neurologist at the MS Centre of Catalonia in Barcelona.
The Emergence of NEDA
A patient receiving treatment who has no sustained disability progression, no relapses, and no new T2 or gadolinium-enhancing lesions has NEDA, as the term was originally conceived. The outcome was rapidly adopted in clinical trials. NEDA also has been applied in the clinical setting. In one study of patients with MS treated in clinical practice, 54% had NEDA at one year. Researchers also found that NEDA may predict long-term outcomes. In one study, 78% of patients with NEDA at year two did not have disease progression at year seven.
A drawback of NEDA is that disease activity may be diffuse and may not manifest itself in relapses, new lesions, or disability progression. “It also may give a false sense of security to the doctor and to the patient,” said Dr. Tintoré.
A fourth factor, brain volume loss, recently was incorporated into NEDA, which has come to be called NEDA-4. Two studies have determined that a 0.4% annual rate of brain volume loss is the best threshold for distinguishing between people with MS and healthy controls.
The Difficulties of NEDA
The new conception of NEDA still omits several factors that neurologists may consider important. NEDA does not take cognition into account, but adding the MS Functional Composite to the NEDA criteria could change that. Patient-reported outcomes such as fatigue, depression, and quality of life also might be appropriate outcomes to incorporate into NEDA, said Dr. Tintoré. In addition, biomarkers such as CSF levels of neurofilament light indicate treatment response and could be added to NEDA.
Current clinical practice may make it difficult to assess whether a patient has NEDA. Many neurologists perform an MRI on a patient before initiating treatment and again at 12 months. “Many of the drugs that we are currently using are not active from baseline,” said Dr. Tintoré. Because changes in the first six months of treatment do not necessarily indicate treatment response, it may be necessary to perform another MRI after several months of treatment as a second baseline measurement, said Dr. Tintoré.
Furthermore, agreement between neuroradiologists is not high. Researchers have observed great variability between readers who had been asked to assess the presence of new T2 or gadolinium-enhancing lesions. And although standardized MRI protocols have been established, they may not be followed uniformly, perhaps because of difficulties specific to given facilities.
Is MEDA an Appropriate Goal?
One potential argument in favor of adopting NEDA as a goal of treatment is that disease activity often predicts poor long-term outcomes. Dr. Tintoré and colleagues assessed the treatment effect in patients with relapsing-remitting MS after two years of interferon therapy. They followed patients for 12 years. Clinical activity during the first two years of treatment was associated with increased risks of developing secondary progressive MS, of reaching an Expanded Disability Status Scale (EDSS) score of 7, and of having a five-point increase on the EDSS at 12 years.
Yet patients with little disease activity may still have good long-term outcomes. In a separate study, Dr. Tintoré and colleagues assessed the presence of MRI lesions after one year in patients with relapsing-remitting MS who were receiving interferon treatment. Participants were followed for eight years, and the primary end point was an increase of at least two points on EDSS after eight years. The investigators found no difference in outcome at eight years between patients who had one gadolinium-enhancing lesion at one year and those who had none at one year. Patients who had two or more gadolinium-enhancing lesions at one year, however, were more likely to reach the primary end point than patients who had fewer than two gadolinium-enhancing lesions at one year.
Results were similar for new T2 lesions. There was no difference in outcome at eight years between participants with no new T2 lesions at one year and those with one or two new T2 lesions at one year. Patients with three or more new T2 lesions at one year, however, were more likely to reach the primary end point. The Rio score was able to predict which patients would have more disability progression, but NEDA was not able to do so, said Dr. Tintoré. These results are similar to those of the MRI in MS (MAGNIMS) data set, in which a low level of disease activity was not associated with poor long-term outcome.
“Combined clinical and MRI scores allow us to integrate disease activity data into individual therapeutic decisions for our patients with MS,” said Dr. Tintoré. Newer therapies have made NEDA attainable for more patients, but not for all patients. Because minimal clinical or MRI activity is not necessarily associated with a poor response in the long term, neurologists may debate whether or when MEDA is an acceptable goal of treatment.
—Erik Greb
Suggested Reading
Giovannoni G, Turner B, Gnanapavan S, et al. Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult Scler Relat Disord. 2015;4(4):329-333.
Kappos L, De Stefano N, Freedman MS, et al. Inclusion of brain volume loss in a revised measure of ‘no evidence of disease activity’ (NEDA-4) in relapsing-remitting multiple sclerosis. Mult Scler. 2016;22(10):1297-1305.
Río J, Castilló J, Rovira A, et al. Measures in the first year of therapy predict the response to interferon beta in MS. Mult Scler. 2009;15(7):848-853.
Uher T, Havrdova E, Sobisek L, et al. Is no evidence of disease activity an achievable goal in MS patients on intramuscular interferon beta-1a treatment over long-term follow-up? Mult Scler. 2016 May 26 [Epub ahead of print].
LONDON—No evidence of disease activity (NEDA) is a worthy but potentially problematic goal in the care of patients with multiple sclerosis (MS), according to an overview provided at the 32nd Congress of the European Committee for Treatment and Research in MS. The definition of NEDA is evolving as neurologists adopt new metrics in clinical practice, and NEDA is a difficult outcome to sustain in the long term.
Studies of interferon beta suggest that a minimal amount of clinical or MRI activity is not necessarily associated with poor long-term outcomes. Such research raises the possibility that minimal evidence of disease activity (MEDA) could be an appropriate goal of treatment, said Mar Tintoré, MD, PhD, neurologist at the MS Centre of Catalonia in Barcelona.
The Emergence of NEDA
A patient receiving treatment who has no sustained disability progression, no relapses, and no new T2 or gadolinium-enhancing lesions has NEDA, as the term was originally conceived. The outcome was rapidly adopted in clinical trials. NEDA also has been applied in the clinical setting. In one study of patients with MS treated in clinical practice, 54% had NEDA at one year. Researchers also found that NEDA may predict long-term outcomes. In one study, 78% of patients with NEDA at year two did not have disease progression at year seven.
A drawback of NEDA is that disease activity may be diffuse and may not manifest itself in relapses, new lesions, or disability progression. “It also may give a false sense of security to the doctor and to the patient,” said Dr. Tintoré.
A fourth factor, brain volume loss, recently was incorporated into NEDA, which has come to be called NEDA-4. Two studies have determined that a 0.4% annual rate of brain volume loss is the best threshold for distinguishing between people with MS and healthy controls.
The Difficulties of NEDA
The new conception of NEDA still omits several factors that neurologists may consider important. NEDA does not take cognition into account, but adding the MS Functional Composite to the NEDA criteria could change that. Patient-reported outcomes such as fatigue, depression, and quality of life also might be appropriate outcomes to incorporate into NEDA, said Dr. Tintoré. In addition, biomarkers such as CSF levels of neurofilament light indicate treatment response and could be added to NEDA.
Current clinical practice may make it difficult to assess whether a patient has NEDA. Many neurologists perform an MRI on a patient before initiating treatment and again at 12 months. “Many of the drugs that we are currently using are not active from baseline,” said Dr. Tintoré. Because changes in the first six months of treatment do not necessarily indicate treatment response, it may be necessary to perform another MRI after several months of treatment as a second baseline measurement, said Dr. Tintoré.
Furthermore, agreement between neuroradiologists is not high. Researchers have observed great variability between readers who had been asked to assess the presence of new T2 or gadolinium-enhancing lesions. And although standardized MRI protocols have been established, they may not be followed uniformly, perhaps because of difficulties specific to given facilities.
Is MEDA an Appropriate Goal?
One potential argument in favor of adopting NEDA as a goal of treatment is that disease activity often predicts poor long-term outcomes. Dr. Tintoré and colleagues assessed the treatment effect in patients with relapsing-remitting MS after two years of interferon therapy. They followed patients for 12 years. Clinical activity during the first two years of treatment was associated with increased risks of developing secondary progressive MS, of reaching an Expanded Disability Status Scale (EDSS) score of 7, and of having a five-point increase on the EDSS at 12 years.
Yet patients with little disease activity may still have good long-term outcomes. In a separate study, Dr. Tintoré and colleagues assessed the presence of MRI lesions after one year in patients with relapsing-remitting MS who were receiving interferon treatment. Participants were followed for eight years, and the primary end point was an increase of at least two points on EDSS after eight years. The investigators found no difference in outcome at eight years between patients who had one gadolinium-enhancing lesion at one year and those who had none at one year. Patients who had two or more gadolinium-enhancing lesions at one year, however, were more likely to reach the primary end point than patients who had fewer than two gadolinium-enhancing lesions at one year.
Results were similar for new T2 lesions. There was no difference in outcome at eight years between participants with no new T2 lesions at one year and those with one or two new T2 lesions at one year. Patients with three or more new T2 lesions at one year, however, were more likely to reach the primary end point. The Rio score was able to predict which patients would have more disability progression, but NEDA was not able to do so, said Dr. Tintoré. These results are similar to those of the MRI in MS (MAGNIMS) data set, in which a low level of disease activity was not associated with poor long-term outcome.
“Combined clinical and MRI scores allow us to integrate disease activity data into individual therapeutic decisions for our patients with MS,” said Dr. Tintoré. Newer therapies have made NEDA attainable for more patients, but not for all patients. Because minimal clinical or MRI activity is not necessarily associated with a poor response in the long term, neurologists may debate whether or when MEDA is an acceptable goal of treatment.
—Erik Greb
Suggested Reading
Giovannoni G, Turner B, Gnanapavan S, et al. Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult Scler Relat Disord. 2015;4(4):329-333.
Kappos L, De Stefano N, Freedman MS, et al. Inclusion of brain volume loss in a revised measure of ‘no evidence of disease activity’ (NEDA-4) in relapsing-remitting multiple sclerosis. Mult Scler. 2016;22(10):1297-1305.
Río J, Castilló J, Rovira A, et al. Measures in the first year of therapy predict the response to interferon beta in MS. Mult Scler. 2009;15(7):848-853.
Uher T, Havrdova E, Sobisek L, et al. Is no evidence of disease activity an achievable goal in MS patients on intramuscular interferon beta-1a treatment over long-term follow-up? Mult Scler. 2016 May 26 [Epub ahead of print].
