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Mitchel is a reporter for MDedge based in the Philadelphia area. He started with the company in 1992, when it was International Medical News Group (IMNG), and has since covered a range of medical specialties. Mitchel trained as a virologist at Roswell Park Memorial Institute in Buffalo, and then worked briefly as a researcher at Boston Children's Hospital before pivoting to journalism as a AAAS Mass Media Fellow in 1980. His first reporting job was with Science Digest magazine, and from the mid-1980s to early-1990s he was a reporter with Medical World News. @mitchelzoler
TNFi treatment halves ankylosing spondylitis progression
MADRID – At least 2 years of tumor necrosis factor–inhibitor treatment of patients with ankylosing spondylitis nearly halved the rate of spinal radiographic progression in a study involving 432 Swiss patients.
In addition, patients on a tumor necrosis factor inhibitor (TNFi) who achieved low disease activity, reflected in an Ankylosing Spondylitis (AS) Disease Activity Score of 1.3 or less, showed virtually no spinal radiographic progression during a 2-year follow-up, Adrian Ciurea, MD, reported at the European Congress of Rheumatology.
He cautioned, however, that the evidence only shows correlation and can’t prove a causal relationship between TNFi treatment and slowed spinal radiographic progression because of potential residual confounding.
Dr. Ciurea and his associates analyzed records for AS patients enrolled in the Swiss Clinical Quality Management in Rheumatic Diseases cohort who underwent at least two spinal radiographs separated by a 2-year gap. They assessed the radiographs using the modified Stoke AS Spinal Score (mSASSS), and they defined progression as a gain of at least two units on the mSASSS during a 2-year period between radiographs.
The 432 AS patients in the study averaged 40 years old, two-thirds were men, and they had AS symptoms for an average of nearly 14 years. Their average AS Disease Activity Score (ASDAS) at entry was 2.8.
A multivariate analysis that controlled for several variables, including sex, smoking history, baseline mSASSS, and exercise, identified three parameters that had significant correlations with radiographic progression: Men had more than double the rate of progression, compared with women; higher baseline mSASSS was linked with a higher rate of progression; and a greater-than-2-year history of treatment with a TNFi was linked with a 48% reduced rate of progression, reported Dr. Ciurea, a rheumatologist at the Zürich University Hospital.
The duration of treatment also mattered. Patients who received at least 4 years of TNFi treatment had a statistically significant 68% reduced rate of radiographic spinal progression. In contrast, patients who received a TNFi for fewer than 4 years but more than 2 years had a 42% lower rate of progression that was of borderline statistical significance. TNFi treatment that started during the 2 years immediately preceding the radiograph failed to show a significant link with reduced progression.
Further analysis also showed a tight correlation between patients’ disease activity while on TNFi treatment and radiographic progression. Patients who maintained an average ASDAS of 2.1 or less during the 2 years prior to radiographic assessment showed an average mSASSS gain of 0.31 units over that 2-year period, compared with an average 1.45-unit mSASSS gain among patients whose average ASDAS remained above 2.1, a statistically significant difference between these two groups. Patients with even more inactive disease on TNFi treatment – those who maintained an average ASDAS of 1.3 or less – had an average 0.01-unit rise in their mSASSS after 2 years of treatment, compared with an average 0.52-unit mSASSS rise after 2 years in patients with an ASDAS of more than 1.3 but less than 2.1, he said.
The cohort study received partial support from Merck Sharpe & Dohme. Dr. Ciurea has been a consultant to or speaker for Abbvie, Celgene, Eli Lilly, Janssen-Cilag, Merck Sharp & Dohme, Novartis, Pfizer, and UCB.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – At least 2 years of tumor necrosis factor–inhibitor treatment of patients with ankylosing spondylitis nearly halved the rate of spinal radiographic progression in a study involving 432 Swiss patients.
In addition, patients on a tumor necrosis factor inhibitor (TNFi) who achieved low disease activity, reflected in an Ankylosing Spondylitis (AS) Disease Activity Score of 1.3 or less, showed virtually no spinal radiographic progression during a 2-year follow-up, Adrian Ciurea, MD, reported at the European Congress of Rheumatology.
He cautioned, however, that the evidence only shows correlation and can’t prove a causal relationship between TNFi treatment and slowed spinal radiographic progression because of potential residual confounding.
Dr. Ciurea and his associates analyzed records for AS patients enrolled in the Swiss Clinical Quality Management in Rheumatic Diseases cohort who underwent at least two spinal radiographs separated by a 2-year gap. They assessed the radiographs using the modified Stoke AS Spinal Score (mSASSS), and they defined progression as a gain of at least two units on the mSASSS during a 2-year period between radiographs.
The 432 AS patients in the study averaged 40 years old, two-thirds were men, and they had AS symptoms for an average of nearly 14 years. Their average AS Disease Activity Score (ASDAS) at entry was 2.8.
A multivariate analysis that controlled for several variables, including sex, smoking history, baseline mSASSS, and exercise, identified three parameters that had significant correlations with radiographic progression: Men had more than double the rate of progression, compared with women; higher baseline mSASSS was linked with a higher rate of progression; and a greater-than-2-year history of treatment with a TNFi was linked with a 48% reduced rate of progression, reported Dr. Ciurea, a rheumatologist at the Zürich University Hospital.
The duration of treatment also mattered. Patients who received at least 4 years of TNFi treatment had a statistically significant 68% reduced rate of radiographic spinal progression. In contrast, patients who received a TNFi for fewer than 4 years but more than 2 years had a 42% lower rate of progression that was of borderline statistical significance. TNFi treatment that started during the 2 years immediately preceding the radiograph failed to show a significant link with reduced progression.
Further analysis also showed a tight correlation between patients’ disease activity while on TNFi treatment and radiographic progression. Patients who maintained an average ASDAS of 2.1 or less during the 2 years prior to radiographic assessment showed an average mSASSS gain of 0.31 units over that 2-year period, compared with an average 1.45-unit mSASSS gain among patients whose average ASDAS remained above 2.1, a statistically significant difference between these two groups. Patients with even more inactive disease on TNFi treatment – those who maintained an average ASDAS of 1.3 or less – had an average 0.01-unit rise in their mSASSS after 2 years of treatment, compared with an average 0.52-unit mSASSS rise after 2 years in patients with an ASDAS of more than 1.3 but less than 2.1, he said.
The cohort study received partial support from Merck Sharpe & Dohme. Dr. Ciurea has been a consultant to or speaker for Abbvie, Celgene, Eli Lilly, Janssen-Cilag, Merck Sharp & Dohme, Novartis, Pfizer, and UCB.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – At least 2 years of tumor necrosis factor–inhibitor treatment of patients with ankylosing spondylitis nearly halved the rate of spinal radiographic progression in a study involving 432 Swiss patients.
In addition, patients on a tumor necrosis factor inhibitor (TNFi) who achieved low disease activity, reflected in an Ankylosing Spondylitis (AS) Disease Activity Score of 1.3 or less, showed virtually no spinal radiographic progression during a 2-year follow-up, Adrian Ciurea, MD, reported at the European Congress of Rheumatology.
He cautioned, however, that the evidence only shows correlation and can’t prove a causal relationship between TNFi treatment and slowed spinal radiographic progression because of potential residual confounding.
Dr. Ciurea and his associates analyzed records for AS patients enrolled in the Swiss Clinical Quality Management in Rheumatic Diseases cohort who underwent at least two spinal radiographs separated by a 2-year gap. They assessed the radiographs using the modified Stoke AS Spinal Score (mSASSS), and they defined progression as a gain of at least two units on the mSASSS during a 2-year period between radiographs.
The 432 AS patients in the study averaged 40 years old, two-thirds were men, and they had AS symptoms for an average of nearly 14 years. Their average AS Disease Activity Score (ASDAS) at entry was 2.8.
A multivariate analysis that controlled for several variables, including sex, smoking history, baseline mSASSS, and exercise, identified three parameters that had significant correlations with radiographic progression: Men had more than double the rate of progression, compared with women; higher baseline mSASSS was linked with a higher rate of progression; and a greater-than-2-year history of treatment with a TNFi was linked with a 48% reduced rate of progression, reported Dr. Ciurea, a rheumatologist at the Zürich University Hospital.
The duration of treatment also mattered. Patients who received at least 4 years of TNFi treatment had a statistically significant 68% reduced rate of radiographic spinal progression. In contrast, patients who received a TNFi for fewer than 4 years but more than 2 years had a 42% lower rate of progression that was of borderline statistical significance. TNFi treatment that started during the 2 years immediately preceding the radiograph failed to show a significant link with reduced progression.
Further analysis also showed a tight correlation between patients’ disease activity while on TNFi treatment and radiographic progression. Patients who maintained an average ASDAS of 2.1 or less during the 2 years prior to radiographic assessment showed an average mSASSS gain of 0.31 units over that 2-year period, compared with an average 1.45-unit mSASSS gain among patients whose average ASDAS remained above 2.1, a statistically significant difference between these two groups. Patients with even more inactive disease on TNFi treatment – those who maintained an average ASDAS of 1.3 or less – had an average 0.01-unit rise in their mSASSS after 2 years of treatment, compared with an average 0.52-unit mSASSS rise after 2 years in patients with an ASDAS of more than 1.3 but less than 2.1, he said.
The cohort study received partial support from Merck Sharpe & Dohme. Dr. Ciurea has been a consultant to or speaker for Abbvie, Celgene, Eli Lilly, Janssen-Cilag, Merck Sharp & Dohme, Novartis, Pfizer, and UCB.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Prolonged TNFi treatment was linked with a 48% lower rate of spinal radiographic progression, compared with shorter treatment.
Data source: Review of 432 patients in the Swiss Clinical Quality Management in Rheumatic Diseases cohort.
Disclosures: The cohort study received partial support from Merck Sharpe & Dohme. Dr. Ciurea has been a consultant to or speaker for Abbvie, Celgene, Eli Lilly, Janssen-Cilag, Merck Sharp & Dohme, Novartis, Pfizer, and UCB.
July 2017: Click for Credit
Here are 6 articles in the July issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. High-dose Oral Vitamin D3 Significantly Reduced Effects of Sunburn
To take the posttest, go to: http://bit.ly/2tmDiKc
Expires May 23, 2018
2. Women Less Likely to Be Diagnosed With Sleep Disorders
To take the posttest, go to: http://bit.ly/2rgLdne
Expires May 30, 2018
3. RA Treatment Delays Raise Risk for Long-term Disability
To take the posttest, go to: http://bit.ly/2tC0IGF
Expires May 30, 2018
4. Target Self-medication of Mood and Anxiety Symptoms
To take the posttest, go to: http://bit.ly/2vy5jel
Expires May 2, 2018
5. Two New Biomarkers for Breast Cancer Show Validity
To take the posttest, go to: http://bit.ly/2ve9H2L
Expires May 2, 2018
6. Time to Therapy for Gram-positive Bacteremia Reduced From 60 Hours to 4 Hours
To take the posttest, go to: http://bit.ly/2ssacIf
Expires May 25, 2018
Here are 6 articles in the July issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. High-dose Oral Vitamin D3 Significantly Reduced Effects of Sunburn
To take the posttest, go to: http://bit.ly/2tmDiKc
Expires May 23, 2018
2. Women Less Likely to Be Diagnosed With Sleep Disorders
To take the posttest, go to: http://bit.ly/2rgLdne
Expires May 30, 2018
3. RA Treatment Delays Raise Risk for Long-term Disability
To take the posttest, go to: http://bit.ly/2tC0IGF
Expires May 30, 2018
4. Target Self-medication of Mood and Anxiety Symptoms
To take the posttest, go to: http://bit.ly/2vy5jel
Expires May 2, 2018
5. Two New Biomarkers for Breast Cancer Show Validity
To take the posttest, go to: http://bit.ly/2ve9H2L
Expires May 2, 2018
6. Time to Therapy for Gram-positive Bacteremia Reduced From 60 Hours to 4 Hours
To take the posttest, go to: http://bit.ly/2ssacIf
Expires May 25, 2018
Here are 6 articles in the July issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. High-dose Oral Vitamin D3 Significantly Reduced Effects of Sunburn
To take the posttest, go to: http://bit.ly/2tmDiKc
Expires May 23, 2018
2. Women Less Likely to Be Diagnosed With Sleep Disorders
To take the posttest, go to: http://bit.ly/2rgLdne
Expires May 30, 2018
3. RA Treatment Delays Raise Risk for Long-term Disability
To take the posttest, go to: http://bit.ly/2tC0IGF
Expires May 30, 2018
4. Target Self-medication of Mood and Anxiety Symptoms
To take the posttest, go to: http://bit.ly/2vy5jel
Expires May 2, 2018
5. Two New Biomarkers for Breast Cancer Show Validity
To take the posttest, go to: http://bit.ly/2ve9H2L
Expires May 2, 2018
6. Time to Therapy for Gram-positive Bacteremia Reduced From 60 Hours to 4 Hours
To take the posttest, go to: http://bit.ly/2ssacIf
Expires May 25, 2018
Do sleep interventions prevent atrial fibrillation?
WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?
Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.
“Only a very small number of patients with atrial fibrillation undergo a sleep study,” he said in an interview. “Before I’d send my mother for atrial fibrillation ablation, I would first look for sleep disordered breathing [SDB],” but this generally isn’t happening routinely. Patients with other types of cardiovascular disease who could potentially benefit from sleep disordered breathing diagnosis and treatment are those with hypertension, especially patients who don’t fully respond to three or more antihypertensive drugs and patients with heart failure with preserved ejection fraction, he added.
Dr. Oldenburg also echoed Dr. Mehra in saying that the evidence supporting this approach for managing atrial fibrillation is less than conclusive.
“We need more precise phenotyping of patients” to better focus on patients with cardiovascular disease and sleep disordered breathing who clearly benefit from CPAP intervention, he said.
Results from the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, reported in September 2016, especially tarnished the notion that treating sleep disordered breathing in patients with various cardiovascular diseases can help avoid future cardiovascular events. The multicenter trial enrolled 2,717 adults with moderate to severe obstructive sleep apnea and cardiovascular disease to receive either CPAP plus optimal routine care or optimal routine care only. After an average follow-up of close to 4 years, the patients treated with CPAP showed no benefit in terms of reduced cardiovascular events (N Engl J Med. 2016 Sept 8;375[10]:919-31).
An editorial that ran with this report suggested that the neutral outcome may have occurred because the average nightly duration of CPAP that patients in the trial self administered was just over 3 hours, arguably an inadequate dose. Other possible reasons for the lack of benefit include the time during their sleep cycle when patients administered CPAP (at the start of sleep rather than later) and that CPAP may have a reduced ability to avert new cardiovascular events in patients with established cardiovascular disease (N Engl J Med. 2016 Sept 8;375[8]:994-6).
Regardless of the reasons, the SAVE results, coupled with the neutral results and suggestion of harm from using adaptive servo-ventilation in patients with heart failure with reduced ejection fraction and central sleep apnea in the SERVE-HF trial (N Engl J Med. 2015 Sept 17;373[12]:1095-105), have thrust the management of SDB in patients with cardiovascular disease back to the point where SDB interventions have no well-proven indications for cardiovascular disease patients.
“With the SERVE-HF and SAVE trials not showing benefit, we now have equipoise” for using or not using SDB interventions in these patients, Dr. Mehra said. “It’s not clear that treating OSA improves outcomes. That allows us to randomize patients to a control placebo arm” in future trials.
An important issue in the failure to clearly establish a role for treating OSA in patients with atrial fibrillation or other cardiovascular diseases may have been over reliance on the apnea-hypopnea index (AHI) as the arbiter of OSA severity, Dr. Oldenburg said. “Maybe there are parameters to look at aside from AHI, perhaps hypoxemia burden or desaturation time. AHI is not the whole truth; we need to look at other parameters. AHI may not be the correct metric to look at in patients with various cardiovascular diseases.”
Her analysis also showed that patients with at least 10 minutes of sleep time with an oxygen saturation rate of 90% or less had a 64% increased rate of later atrial fibrillation hospitalizations, compared with those with fewer than 10 minutes spent in this state. Nearly a quarter of the patients studied fell into this category.
“Nocturnal oxygen desaturation may be stronger than AHI for predicting atrial fibrillation development,” Dr. Kendzerska concluded. “The severity of OSA-related intermittent hypoxia may be more important than sleep fragmentation in the development of atrial fibrillation. These findings support a relationship between OSA, chronic nocturnal hypoxemia, and new onset atrial fibrillation.”
However, using oxygen desaturation instead of AHI to gauge the severity of OSA won’t solve all the challenges that sleep researchers currently face in trying to determine the efficacy of breathing interventions to prevent or treat cardiovascular disease. In the neutral SAVE trial, researchers used nocturnal oxygen saturation levels to select patients with clinically meaningful OSA.
Dr. Mehra and Dr. Kendzerska had no disclosures. Dr. Oldenburg has received consultant fees, honoraria, and/or research support from ResMed, Respicardia, and Weinmann.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This article was updated on 7/10/17.
WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?
Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.
“Only a very small number of patients with atrial fibrillation undergo a sleep study,” he said in an interview. “Before I’d send my mother for atrial fibrillation ablation, I would first look for sleep disordered breathing [SDB],” but this generally isn’t happening routinely. Patients with other types of cardiovascular disease who could potentially benefit from sleep disordered breathing diagnosis and treatment are those with hypertension, especially patients who don’t fully respond to three or more antihypertensive drugs and patients with heart failure with preserved ejection fraction, he added.
Dr. Oldenburg also echoed Dr. Mehra in saying that the evidence supporting this approach for managing atrial fibrillation is less than conclusive.
“We need more precise phenotyping of patients” to better focus on patients with cardiovascular disease and sleep disordered breathing who clearly benefit from CPAP intervention, he said.
Results from the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, reported in September 2016, especially tarnished the notion that treating sleep disordered breathing in patients with various cardiovascular diseases can help avoid future cardiovascular events. The multicenter trial enrolled 2,717 adults with moderate to severe obstructive sleep apnea and cardiovascular disease to receive either CPAP plus optimal routine care or optimal routine care only. After an average follow-up of close to 4 years, the patients treated with CPAP showed no benefit in terms of reduced cardiovascular events (N Engl J Med. 2016 Sept 8;375[10]:919-31).
An editorial that ran with this report suggested that the neutral outcome may have occurred because the average nightly duration of CPAP that patients in the trial self administered was just over 3 hours, arguably an inadequate dose. Other possible reasons for the lack of benefit include the time during their sleep cycle when patients administered CPAP (at the start of sleep rather than later) and that CPAP may have a reduced ability to avert new cardiovascular events in patients with established cardiovascular disease (N Engl J Med. 2016 Sept 8;375[8]:994-6).
Regardless of the reasons, the SAVE results, coupled with the neutral results and suggestion of harm from using adaptive servo-ventilation in patients with heart failure with reduced ejection fraction and central sleep apnea in the SERVE-HF trial (N Engl J Med. 2015 Sept 17;373[12]:1095-105), have thrust the management of SDB in patients with cardiovascular disease back to the point where SDB interventions have no well-proven indications for cardiovascular disease patients.
“With the SERVE-HF and SAVE trials not showing benefit, we now have equipoise” for using or not using SDB interventions in these patients, Dr. Mehra said. “It’s not clear that treating OSA improves outcomes. That allows us to randomize patients to a control placebo arm” in future trials.
An important issue in the failure to clearly establish a role for treating OSA in patients with atrial fibrillation or other cardiovascular diseases may have been over reliance on the apnea-hypopnea index (AHI) as the arbiter of OSA severity, Dr. Oldenburg said. “Maybe there are parameters to look at aside from AHI, perhaps hypoxemia burden or desaturation time. AHI is not the whole truth; we need to look at other parameters. AHI may not be the correct metric to look at in patients with various cardiovascular diseases.”
Her analysis also showed that patients with at least 10 minutes of sleep time with an oxygen saturation rate of 90% or less had a 64% increased rate of later atrial fibrillation hospitalizations, compared with those with fewer than 10 minutes spent in this state. Nearly a quarter of the patients studied fell into this category.
“Nocturnal oxygen desaturation may be stronger than AHI for predicting atrial fibrillation development,” Dr. Kendzerska concluded. “The severity of OSA-related intermittent hypoxia may be more important than sleep fragmentation in the development of atrial fibrillation. These findings support a relationship between OSA, chronic nocturnal hypoxemia, and new onset atrial fibrillation.”
However, using oxygen desaturation instead of AHI to gauge the severity of OSA won’t solve all the challenges that sleep researchers currently face in trying to determine the efficacy of breathing interventions to prevent or treat cardiovascular disease. In the neutral SAVE trial, researchers used nocturnal oxygen saturation levels to select patients with clinically meaningful OSA.
Dr. Mehra and Dr. Kendzerska had no disclosures. Dr. Oldenburg has received consultant fees, honoraria, and/or research support from ResMed, Respicardia, and Weinmann.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This article was updated on 7/10/17.
WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?
Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.
“Only a very small number of patients with atrial fibrillation undergo a sleep study,” he said in an interview. “Before I’d send my mother for atrial fibrillation ablation, I would first look for sleep disordered breathing [SDB],” but this generally isn’t happening routinely. Patients with other types of cardiovascular disease who could potentially benefit from sleep disordered breathing diagnosis and treatment are those with hypertension, especially patients who don’t fully respond to three or more antihypertensive drugs and patients with heart failure with preserved ejection fraction, he added.
Dr. Oldenburg also echoed Dr. Mehra in saying that the evidence supporting this approach for managing atrial fibrillation is less than conclusive.
“We need more precise phenotyping of patients” to better focus on patients with cardiovascular disease and sleep disordered breathing who clearly benefit from CPAP intervention, he said.
Results from the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, reported in September 2016, especially tarnished the notion that treating sleep disordered breathing in patients with various cardiovascular diseases can help avoid future cardiovascular events. The multicenter trial enrolled 2,717 adults with moderate to severe obstructive sleep apnea and cardiovascular disease to receive either CPAP plus optimal routine care or optimal routine care only. After an average follow-up of close to 4 years, the patients treated with CPAP showed no benefit in terms of reduced cardiovascular events (N Engl J Med. 2016 Sept 8;375[10]:919-31).
An editorial that ran with this report suggested that the neutral outcome may have occurred because the average nightly duration of CPAP that patients in the trial self administered was just over 3 hours, arguably an inadequate dose. Other possible reasons for the lack of benefit include the time during their sleep cycle when patients administered CPAP (at the start of sleep rather than later) and that CPAP may have a reduced ability to avert new cardiovascular events in patients with established cardiovascular disease (N Engl J Med. 2016 Sept 8;375[8]:994-6).
Regardless of the reasons, the SAVE results, coupled with the neutral results and suggestion of harm from using adaptive servo-ventilation in patients with heart failure with reduced ejection fraction and central sleep apnea in the SERVE-HF trial (N Engl J Med. 2015 Sept 17;373[12]:1095-105), have thrust the management of SDB in patients with cardiovascular disease back to the point where SDB interventions have no well-proven indications for cardiovascular disease patients.
“With the SERVE-HF and SAVE trials not showing benefit, we now have equipoise” for using or not using SDB interventions in these patients, Dr. Mehra said. “It’s not clear that treating OSA improves outcomes. That allows us to randomize patients to a control placebo arm” in future trials.
An important issue in the failure to clearly establish a role for treating OSA in patients with atrial fibrillation or other cardiovascular diseases may have been over reliance on the apnea-hypopnea index (AHI) as the arbiter of OSA severity, Dr. Oldenburg said. “Maybe there are parameters to look at aside from AHI, perhaps hypoxemia burden or desaturation time. AHI is not the whole truth; we need to look at other parameters. AHI may not be the correct metric to look at in patients with various cardiovascular diseases.”
Her analysis also showed that patients with at least 10 minutes of sleep time with an oxygen saturation rate of 90% or less had a 64% increased rate of later atrial fibrillation hospitalizations, compared with those with fewer than 10 minutes spent in this state. Nearly a quarter of the patients studied fell into this category.
“Nocturnal oxygen desaturation may be stronger than AHI for predicting atrial fibrillation development,” Dr. Kendzerska concluded. “The severity of OSA-related intermittent hypoxia may be more important than sleep fragmentation in the development of atrial fibrillation. These findings support a relationship between OSA, chronic nocturnal hypoxemia, and new onset atrial fibrillation.”
However, using oxygen desaturation instead of AHI to gauge the severity of OSA won’t solve all the challenges that sleep researchers currently face in trying to determine the efficacy of breathing interventions to prevent or treat cardiovascular disease. In the neutral SAVE trial, researchers used nocturnal oxygen saturation levels to select patients with clinically meaningful OSA.
Dr. Mehra and Dr. Kendzerska had no disclosures. Dr. Oldenburg has received consultant fees, honoraria, and/or research support from ResMed, Respicardia, and Weinmann.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This article was updated on 7/10/17.
EXPERT ANALYSIS FROM ATS 2017
VIDEO: Hip, knee replacements fall in Danish RA patients
MADRID – The rates of both total hip and total knee replacement surgeries dropped among Danish patients with rheumatoid arthritis since the mid-1990s, reductions that were coincident with more widespread use of biologic drugs as well as with other improvements in care, according to analyses of Danish national health records.
“The introduction of guidelines [on biologic drug use] in 2002 and increasing use of biologic drugs [as a result] may have contributed to this positive development,” Lene Dreyer, MD, said at the European Congress of Rheumatology. Other factors that may have also contributed include widespread use of conventional disease-modifying antirheumatic drugs (DMARDs) and adoption of a treat-to-target strategy by many clinicians.
In 1996, the first year studied and before any biologic DMARDs were routinely used for rheumatoid arthritis, the rate of total knee replacement was nearly 6/1,000 person-years among RA patients, compared with a 0.42/1,000 person-years rate in the general adult Danish population, a roughly 14-fold excess among the RA patients, Dr. Dreyer reported. But by 2016, ”this gap had almost disappeared,” she said in a video interview. “It seems like rheumatologists in Denmark are doing a good job” treating RA patients.
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That may have been especially true subsequent to 2002, when the Danish Institute for Rational Pharmacotherapy issued recommendations that opened the door to wider use of biologic DMARDs, such as tumor necrosis factor inhibitors, to treat RA patients, noted Dr. Dreyer of Gentofte University Hospital, Copenhagen. During 2003-2011, use of total knee replacement surgery in RA patients fell by an average annualized rate of 0.2 surgeries/1,000 person-years. But among the general Danish population the average annualized rate of knee surgeries rose by 0.08/1,000 person-years.
“This is a very important finding,” commented Robert Landewé, MD, PhD, professor of rheumatology at the Academic Medical Center in Amsterdam. “It is extremely difficult to test the effect of the introduction of the [biologic DMARD] guidelines,” he cautioned. But he highlighted the positive finding that the excess of hip and knee replacement surgeries in patients with RA, compared with the general population, had recently narrowed.
Dr. Dreyer and her associates used records from the Danish National Patient Register to compare 29,427 patients with incident RA during 1996-2011 with more than 290,000 matched control individuals. All people studied had not undergone knee or hip replacement surgery prior to their entry into the study. The researchers used an “interrupted time series analysis” to examine the possible impact of the introduction of widespread access to biologic DMARDs starting in 2003.
The analysis showed that the rate of total hip replacements in 1996 was nearly 9 surgeries/1,000 person-years among RA patients and nearly 3/1,000 person-years in the general population, a threefold excess for RA patients. This rate fell by an average annual rate of 0.38/1,000 person-years among RA patients both before and after 2002, so that by 2011 the rate was roughly half the 1996 rate, about 4.5/1,000 patient-years. The rate in the general population rose during 1996-2011, and by 2011 was nearly 4/1,000 person-years and so nearly the same as RA patients. Wider availability of biologic DMARDs for RA patients starting in 2003 did not have an apparent impact on the rate of total hip replacement.
In contrast, wider use of biologic DMARDs appeared to have an effect on the rate of total knee surgeries among RA patients. During 1996-2001, the rate rose by an annual average of 0.19/1,000 person-years, very similar to the 0.21/1,000 person-years annual rise in the general Danish population. However, during 2003-2011, the average annual rate of total knee surgery fell by 0.20/1,000 person-years in the RA patients but continued to rise at an annual average rate of 0.08/1,000 person-years in the general population, Dr. Dreyer reported.
Additional Danish registry data exist for patients who received biologic DMARDs, and Dr. Dreyer said that she and her associates hope to use this to further examine the impact of these drugs on patient outcomes.
Dr. Dreyer has received lecture fees from Merck Sharp & Dohme and UCB. Dr. Landewé has received consulting fees from several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – The rates of both total hip and total knee replacement surgeries dropped among Danish patients with rheumatoid arthritis since the mid-1990s, reductions that were coincident with more widespread use of biologic drugs as well as with other improvements in care, according to analyses of Danish national health records.
“The introduction of guidelines [on biologic drug use] in 2002 and increasing use of biologic drugs [as a result] may have contributed to this positive development,” Lene Dreyer, MD, said at the European Congress of Rheumatology. Other factors that may have also contributed include widespread use of conventional disease-modifying antirheumatic drugs (DMARDs) and adoption of a treat-to-target strategy by many clinicians.
In 1996, the first year studied and before any biologic DMARDs were routinely used for rheumatoid arthritis, the rate of total knee replacement was nearly 6/1,000 person-years among RA patients, compared with a 0.42/1,000 person-years rate in the general adult Danish population, a roughly 14-fold excess among the RA patients, Dr. Dreyer reported. But by 2016, ”this gap had almost disappeared,” she said in a video interview. “It seems like rheumatologists in Denmark are doing a good job” treating RA patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
That may have been especially true subsequent to 2002, when the Danish Institute for Rational Pharmacotherapy issued recommendations that opened the door to wider use of biologic DMARDs, such as tumor necrosis factor inhibitors, to treat RA patients, noted Dr. Dreyer of Gentofte University Hospital, Copenhagen. During 2003-2011, use of total knee replacement surgery in RA patients fell by an average annualized rate of 0.2 surgeries/1,000 person-years. But among the general Danish population the average annualized rate of knee surgeries rose by 0.08/1,000 person-years.
“This is a very important finding,” commented Robert Landewé, MD, PhD, professor of rheumatology at the Academic Medical Center in Amsterdam. “It is extremely difficult to test the effect of the introduction of the [biologic DMARD] guidelines,” he cautioned. But he highlighted the positive finding that the excess of hip and knee replacement surgeries in patients with RA, compared with the general population, had recently narrowed.
Dr. Dreyer and her associates used records from the Danish National Patient Register to compare 29,427 patients with incident RA during 1996-2011 with more than 290,000 matched control individuals. All people studied had not undergone knee or hip replacement surgery prior to their entry into the study. The researchers used an “interrupted time series analysis” to examine the possible impact of the introduction of widespread access to biologic DMARDs starting in 2003.
The analysis showed that the rate of total hip replacements in 1996 was nearly 9 surgeries/1,000 person-years among RA patients and nearly 3/1,000 person-years in the general population, a threefold excess for RA patients. This rate fell by an average annual rate of 0.38/1,000 person-years among RA patients both before and after 2002, so that by 2011 the rate was roughly half the 1996 rate, about 4.5/1,000 patient-years. The rate in the general population rose during 1996-2011, and by 2011 was nearly 4/1,000 person-years and so nearly the same as RA patients. Wider availability of biologic DMARDs for RA patients starting in 2003 did not have an apparent impact on the rate of total hip replacement.
In contrast, wider use of biologic DMARDs appeared to have an effect on the rate of total knee surgeries among RA patients. During 1996-2001, the rate rose by an annual average of 0.19/1,000 person-years, very similar to the 0.21/1,000 person-years annual rise in the general Danish population. However, during 2003-2011, the average annual rate of total knee surgery fell by 0.20/1,000 person-years in the RA patients but continued to rise at an annual average rate of 0.08/1,000 person-years in the general population, Dr. Dreyer reported.
Additional Danish registry data exist for patients who received biologic DMARDs, and Dr. Dreyer said that she and her associates hope to use this to further examine the impact of these drugs on patient outcomes.
Dr. Dreyer has received lecture fees from Merck Sharp & Dohme and UCB. Dr. Landewé has received consulting fees from several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – The rates of both total hip and total knee replacement surgeries dropped among Danish patients with rheumatoid arthritis since the mid-1990s, reductions that were coincident with more widespread use of biologic drugs as well as with other improvements in care, according to analyses of Danish national health records.
“The introduction of guidelines [on biologic drug use] in 2002 and increasing use of biologic drugs [as a result] may have contributed to this positive development,” Lene Dreyer, MD, said at the European Congress of Rheumatology. Other factors that may have also contributed include widespread use of conventional disease-modifying antirheumatic drugs (DMARDs) and adoption of a treat-to-target strategy by many clinicians.
In 1996, the first year studied and before any biologic DMARDs were routinely used for rheumatoid arthritis, the rate of total knee replacement was nearly 6/1,000 person-years among RA patients, compared with a 0.42/1,000 person-years rate in the general adult Danish population, a roughly 14-fold excess among the RA patients, Dr. Dreyer reported. But by 2016, ”this gap had almost disappeared,” she said in a video interview. “It seems like rheumatologists in Denmark are doing a good job” treating RA patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
That may have been especially true subsequent to 2002, when the Danish Institute for Rational Pharmacotherapy issued recommendations that opened the door to wider use of biologic DMARDs, such as tumor necrosis factor inhibitors, to treat RA patients, noted Dr. Dreyer of Gentofte University Hospital, Copenhagen. During 2003-2011, use of total knee replacement surgery in RA patients fell by an average annualized rate of 0.2 surgeries/1,000 person-years. But among the general Danish population the average annualized rate of knee surgeries rose by 0.08/1,000 person-years.
“This is a very important finding,” commented Robert Landewé, MD, PhD, professor of rheumatology at the Academic Medical Center in Amsterdam. “It is extremely difficult to test the effect of the introduction of the [biologic DMARD] guidelines,” he cautioned. But he highlighted the positive finding that the excess of hip and knee replacement surgeries in patients with RA, compared with the general population, had recently narrowed.
Dr. Dreyer and her associates used records from the Danish National Patient Register to compare 29,427 patients with incident RA during 1996-2011 with more than 290,000 matched control individuals. All people studied had not undergone knee or hip replacement surgery prior to their entry into the study. The researchers used an “interrupted time series analysis” to examine the possible impact of the introduction of widespread access to biologic DMARDs starting in 2003.
The analysis showed that the rate of total hip replacements in 1996 was nearly 9 surgeries/1,000 person-years among RA patients and nearly 3/1,000 person-years in the general population, a threefold excess for RA patients. This rate fell by an average annual rate of 0.38/1,000 person-years among RA patients both before and after 2002, so that by 2011 the rate was roughly half the 1996 rate, about 4.5/1,000 patient-years. The rate in the general population rose during 1996-2011, and by 2011 was nearly 4/1,000 person-years and so nearly the same as RA patients. Wider availability of biologic DMARDs for RA patients starting in 2003 did not have an apparent impact on the rate of total hip replacement.
In contrast, wider use of biologic DMARDs appeared to have an effect on the rate of total knee surgeries among RA patients. During 1996-2001, the rate rose by an annual average of 0.19/1,000 person-years, very similar to the 0.21/1,000 person-years annual rise in the general Danish population. However, during 2003-2011, the average annual rate of total knee surgery fell by 0.20/1,000 person-years in the RA patients but continued to rise at an annual average rate of 0.08/1,000 person-years in the general population, Dr. Dreyer reported.
Additional Danish registry data exist for patients who received biologic DMARDs, and Dr. Dreyer said that she and her associates hope to use this to further examine the impact of these drugs on patient outcomes.
Dr. Dreyer has received lecture fees from Merck Sharp & Dohme and UCB. Dr. Landewé has received consulting fees from several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: RA patient hip replacements fell from nearly 9/1,000 person-years in 1996 to about 4.5/1,000 person-years in 2011.
Data source: Records from more than 300,000 people in the Danish National Patient Register.
Disclosures: Dr. Dreyer has received lecture fees from Merck Sharp & Dohme and UCB. Dr. Landewé has received consulting fees from several drug companies.
Obesity blunts TNFi response in axial spondyloarthritis
MADRID – Obese patients with axial spondyloarthritis were substantially less responsive to treatment with a tumor necrosis factor inhibitor than were healthy-weight patients in a multicenter Swiss study with 531 patients.
In a multivariate analysis that controlled for several demographic and clinical factors, including baseline disease severity, obese patients with axial spondyloarthritis (SpA) were 70% less likely to achieve a 40% or better improvement in their Assessment in SpondyloArthritis International Society improvement criteria (ASAS 40) when compared with patients with a healthy body mass index (BMI), Raphael Micheroli, MD, reported in a poster at the European Congress of Rheumatology.
The finding supplies a third reason why patients with newly diagnosed axial SpA should try to lose weight if they are obese (or overweight) – to potentially improve their responsiveness to a TNFi. The other two reasons are to reduce cardiovascular disease risk in patients who are already at risk for these complications because of their disease, and to also help improve their ability to perform physical activities, he explained in an interview.
Dr. Micheroli proposed three possible reasons why obese patients with axial SpA might be less responsive to a TNFi than healthy-weight patients: They receive an inadequate TNFi dosage, their increased adipose tissue produces excess proinflammatory cytokines that exacerbate their axial SpA, or it is possible that obese patients are more likely to be misdiagnosed with axial SpA and because they don’t really have this disease their symptoms cannot improve with TNFi treatment. They may instead have, for example, degenerative back pain, a condition that can be challenging to distinguish from axial SpA, he said.
A role for obesity in blunting the beneficial effects of TNFi treatment has been well described for psoriatic arthritis, for example, in an Italian study with 138 patients (Ann Rheum Dis. 2014 June;73[6]:1157-62), and in a Danish study with more than 1,200 patients (Rheumatology [Oxford]. 2016 Dec;55[12]:2191-9).
Dr. Micheroli’s study included 624 patients with axial SpA enrolled in the Swiss Clinical Quality Management in Rheumatic Diseases axial spondyloarthritis cohort who met the ASAS classification criteria for axial SpA and started treatment with their first TNFi after they entered the cohort. Follow-up data after 1 year on treatment were available for 531 of these patients. The entry group included 332 patients (53%) with a healthy BMI, 204 (33%) with an overweight BMI (25-30 kg/m2), and 88 (14%) obese patients (BMI more than 30 kg/m2). The patients averaged about 40 years old and had been symptomatic for an average of about 13 years. About one-third of patients started on adalimumab (Humira) treatment, about one-quarter started etanercept (Enbrel), more than one-fifth began infliximab (Remicade), and some patients started treatment with either golimumab (Simponi) or certolizumab pegol (Cimzia).
After 1 year on TNFi treatment, ASAS 40 improvement occurred in 44% of 282 healthy-BMI patients, 34% of 178 overweight patients, and in 29% of 71 obese patients, Dr. Micheroli reported. In a baseline-adjusted multivariate model, this difference translated into an odds ratio of 0.30 for obese patients achieving an ASAS 40 response, compared with the healthy-BMI patients after 1 year, a statistically significant difference. Further analysis showed no statistically significant differences in TNFi discontinuation rates among the three BMI subgroups.
Dr. Micheroli had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – Obese patients with axial spondyloarthritis were substantially less responsive to treatment with a tumor necrosis factor inhibitor than were healthy-weight patients in a multicenter Swiss study with 531 patients.
In a multivariate analysis that controlled for several demographic and clinical factors, including baseline disease severity, obese patients with axial spondyloarthritis (SpA) were 70% less likely to achieve a 40% or better improvement in their Assessment in SpondyloArthritis International Society improvement criteria (ASAS 40) when compared with patients with a healthy body mass index (BMI), Raphael Micheroli, MD, reported in a poster at the European Congress of Rheumatology.
The finding supplies a third reason why patients with newly diagnosed axial SpA should try to lose weight if they are obese (or overweight) – to potentially improve their responsiveness to a TNFi. The other two reasons are to reduce cardiovascular disease risk in patients who are already at risk for these complications because of their disease, and to also help improve their ability to perform physical activities, he explained in an interview.
Dr. Micheroli proposed three possible reasons why obese patients with axial SpA might be less responsive to a TNFi than healthy-weight patients: They receive an inadequate TNFi dosage, their increased adipose tissue produces excess proinflammatory cytokines that exacerbate their axial SpA, or it is possible that obese patients are more likely to be misdiagnosed with axial SpA and because they don’t really have this disease their symptoms cannot improve with TNFi treatment. They may instead have, for example, degenerative back pain, a condition that can be challenging to distinguish from axial SpA, he said.
A role for obesity in blunting the beneficial effects of TNFi treatment has been well described for psoriatic arthritis, for example, in an Italian study with 138 patients (Ann Rheum Dis. 2014 June;73[6]:1157-62), and in a Danish study with more than 1,200 patients (Rheumatology [Oxford]. 2016 Dec;55[12]:2191-9).
Dr. Micheroli’s study included 624 patients with axial SpA enrolled in the Swiss Clinical Quality Management in Rheumatic Diseases axial spondyloarthritis cohort who met the ASAS classification criteria for axial SpA and started treatment with their first TNFi after they entered the cohort. Follow-up data after 1 year on treatment were available for 531 of these patients. The entry group included 332 patients (53%) with a healthy BMI, 204 (33%) with an overweight BMI (25-30 kg/m2), and 88 (14%) obese patients (BMI more than 30 kg/m2). The patients averaged about 40 years old and had been symptomatic for an average of about 13 years. About one-third of patients started on adalimumab (Humira) treatment, about one-quarter started etanercept (Enbrel), more than one-fifth began infliximab (Remicade), and some patients started treatment with either golimumab (Simponi) or certolizumab pegol (Cimzia).
After 1 year on TNFi treatment, ASAS 40 improvement occurred in 44% of 282 healthy-BMI patients, 34% of 178 overweight patients, and in 29% of 71 obese patients, Dr. Micheroli reported. In a baseline-adjusted multivariate model, this difference translated into an odds ratio of 0.30 for obese patients achieving an ASAS 40 response, compared with the healthy-BMI patients after 1 year, a statistically significant difference. Further analysis showed no statistically significant differences in TNFi discontinuation rates among the three BMI subgroups.
Dr. Micheroli had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – Obese patients with axial spondyloarthritis were substantially less responsive to treatment with a tumor necrosis factor inhibitor than were healthy-weight patients in a multicenter Swiss study with 531 patients.
In a multivariate analysis that controlled for several demographic and clinical factors, including baseline disease severity, obese patients with axial spondyloarthritis (SpA) were 70% less likely to achieve a 40% or better improvement in their Assessment in SpondyloArthritis International Society improvement criteria (ASAS 40) when compared with patients with a healthy body mass index (BMI), Raphael Micheroli, MD, reported in a poster at the European Congress of Rheumatology.
The finding supplies a third reason why patients with newly diagnosed axial SpA should try to lose weight if they are obese (or overweight) – to potentially improve their responsiveness to a TNFi. The other two reasons are to reduce cardiovascular disease risk in patients who are already at risk for these complications because of their disease, and to also help improve their ability to perform physical activities, he explained in an interview.
Dr. Micheroli proposed three possible reasons why obese patients with axial SpA might be less responsive to a TNFi than healthy-weight patients: They receive an inadequate TNFi dosage, their increased adipose tissue produces excess proinflammatory cytokines that exacerbate their axial SpA, or it is possible that obese patients are more likely to be misdiagnosed with axial SpA and because they don’t really have this disease their symptoms cannot improve with TNFi treatment. They may instead have, for example, degenerative back pain, a condition that can be challenging to distinguish from axial SpA, he said.
A role for obesity in blunting the beneficial effects of TNFi treatment has been well described for psoriatic arthritis, for example, in an Italian study with 138 patients (Ann Rheum Dis. 2014 June;73[6]:1157-62), and in a Danish study with more than 1,200 patients (Rheumatology [Oxford]. 2016 Dec;55[12]:2191-9).
Dr. Micheroli’s study included 624 patients with axial SpA enrolled in the Swiss Clinical Quality Management in Rheumatic Diseases axial spondyloarthritis cohort who met the ASAS classification criteria for axial SpA and started treatment with their first TNFi after they entered the cohort. Follow-up data after 1 year on treatment were available for 531 of these patients. The entry group included 332 patients (53%) with a healthy BMI, 204 (33%) with an overweight BMI (25-30 kg/m2), and 88 (14%) obese patients (BMI more than 30 kg/m2). The patients averaged about 40 years old and had been symptomatic for an average of about 13 years. About one-third of patients started on adalimumab (Humira) treatment, about one-quarter started etanercept (Enbrel), more than one-fifth began infliximab (Remicade), and some patients started treatment with either golimumab (Simponi) or certolizumab pegol (Cimzia).
After 1 year on TNFi treatment, ASAS 40 improvement occurred in 44% of 282 healthy-BMI patients, 34% of 178 overweight patients, and in 29% of 71 obese patients, Dr. Micheroli reported. In a baseline-adjusted multivariate model, this difference translated into an odds ratio of 0.30 for obese patients achieving an ASAS 40 response, compared with the healthy-BMI patients after 1 year, a statistically significant difference. Further analysis showed no statistically significant differences in TNFi discontinuation rates among the three BMI subgroups.
Dr. Micheroli had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Obese patients had a 70% lower response rate to a tumor necrosis factor inhibitor, compared with healthy-weight patients.
Data source: A cohort of 531 axial spondyloarthritis patients enrolled in the Swiss Clinical Quality Management in Rheumatic Diseases program.
Disclosures: Dr. Micheroli had no disclosures.
VIDEO: Cancer immunotherapies activate rheumatologic adverse effects
MADRID – The introduction of immune checkpoint inhibitor drugs has “been great for cancer but bad for rheumatology.”
That’s the gist of the immunologic adverse effect fallout from the immunomodulatory revolution that’s recently swept oncology, Leonard Calabrese, DO, said in a video interview during the European Congress of Rheumatology.
Results from a recent survey of U.S. rheumatologists run by Dr. Calabrese and his associates showed that “more than a quarter” now have seen at least one patient who experienced activation of a rheumatologic disease after starting treatment with an immune checkpoint inhibitor, said Dr. Calabrese, head of the section of clinical immunology at the Cleveland Clinic in Ohio.
Unlike most other immunological adverse effects caused by immune checkpoint inhibitors, the rheumatologic complications usually don’t resolve when treatment stops, he added.
These adverse effects represent a new wrinkle for the practice of rheumatology and are now something that clinicians must familiarize themselves with, Dr. Calabrese advised.
Dr. Calabrese reported that he is a consultant to Bristol-Myers Squibb.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – The introduction of immune checkpoint inhibitor drugs has “been great for cancer but bad for rheumatology.”
That’s the gist of the immunologic adverse effect fallout from the immunomodulatory revolution that’s recently swept oncology, Leonard Calabrese, DO, said in a video interview during the European Congress of Rheumatology.
Results from a recent survey of U.S. rheumatologists run by Dr. Calabrese and his associates showed that “more than a quarter” now have seen at least one patient who experienced activation of a rheumatologic disease after starting treatment with an immune checkpoint inhibitor, said Dr. Calabrese, head of the section of clinical immunology at the Cleveland Clinic in Ohio.
Unlike most other immunological adverse effects caused by immune checkpoint inhibitors, the rheumatologic complications usually don’t resolve when treatment stops, he added.
These adverse effects represent a new wrinkle for the practice of rheumatology and are now something that clinicians must familiarize themselves with, Dr. Calabrese advised.
Dr. Calabrese reported that he is a consultant to Bristol-Myers Squibb.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – The introduction of immune checkpoint inhibitor drugs has “been great for cancer but bad for rheumatology.”
That’s the gist of the immunologic adverse effect fallout from the immunomodulatory revolution that’s recently swept oncology, Leonard Calabrese, DO, said in a video interview during the European Congress of Rheumatology.
Results from a recent survey of U.S. rheumatologists run by Dr. Calabrese and his associates showed that “more than a quarter” now have seen at least one patient who experienced activation of a rheumatologic disease after starting treatment with an immune checkpoint inhibitor, said Dr. Calabrese, head of the section of clinical immunology at the Cleveland Clinic in Ohio.
Unlike most other immunological adverse effects caused by immune checkpoint inhibitors, the rheumatologic complications usually don’t resolve when treatment stops, he added.
These adverse effects represent a new wrinkle for the practice of rheumatology and are now something that clinicians must familiarize themselves with, Dr. Calabrese advised.
Dr. Calabrese reported that he is a consultant to Bristol-Myers Squibb.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE EULAR 2017 CONGRESS
Mesenchymal precursor cells simmer down rheumatoid arthritis
MADRID – A single injection of allogeneic mesenchymal precursor cells was apparently both safe and effective for relieving some symptoms of rheumatoid arthritis in biological-refractory patients in a phase II randomized trial with 48 patients.
Most of the efficacy measures ran out to 12 weeks, but researchers followed one measure, the American College of Rheumatology N (ACR-N) index of improvement, out to 39 weeks after a single infusion, and this measure showed a statistically significant, durable benefit from the higher tested dose of mesenchymal precursor cells (MPC) when compared with placebo, Suzanne Kafaja, MD, said while presenting a poster at the European Congress of Rheumatology.
“The trial met its primary endpoints, and so far the data look pretty encouraging, but it’s still pretty early,” she said.
“I was surprised by the durability” of the anti-inflammatory effect of the MPC at 39 weeks, Dr. Kafaja added in an interview.
The study, run at 16 U.S. centers and 2 sites in Australia, enrolled 48 patients with rheumatoid arthritis and on a stable methotrexate regimen for at least 4 months who had a history of failing to adequately respond to at least one biological disease-modifying drug, most commonly a tumor necrosis factor inhibitor. The average age of the enrolled patients was 55 years; nearly three-quarters were women. The patients had been diagnosed with rheumatoid arthritis for an average of 13 years, and more than one-third of the patients had a history of inadequate response to three or more biological agents.
Thirty-six of the patients received a single infusion of a preparation of MPC taken from the bone marrow of healthy donors and isolated and expanded ex vivo. Half the patients in the active-treatment group received 1 million MPC per kg, and the other half received 2 million MPC per kg. An additional 16 patients received placebo. The researchers obtained the MPC from Mesoblast Limited, an Australia-based company that sponsored the study and uses a proprietary method for MPC processing to produce an “off-the-shelf” product.
The allogeneic MPC used in the study is a homogeneous population of cells that respond to pro-inflammatory cytokines by releasing cytokines of their own that induce monocytes and T-cells into an anti-inflammatory state.
The treatment groups showed no difference, compared with the placebo group, for the ACR20, ACR50, and ACR70 measurements, but for two other measures, the Health Assessment Questionnaire and the 28-joint Disease Activity Score, the results showed trends toward dose-related improvements following MPC treatment. The results showed statistically significant improvements after 12 and 39 weeks in average ACR-N in the patients who received 2 million MPC per kg. After 39 weeks, the average ACR-N improvement rate was about 35% among patients who had received 2 million MPC per kg, about 10% among those who received 1 million cells per kg, and about 8% among placebo patients, Dr. Kafaja reported.
Mesoblast funded the study. Dr. Kafaja had no other disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – A single injection of allogeneic mesenchymal precursor cells was apparently both safe and effective for relieving some symptoms of rheumatoid arthritis in biological-refractory patients in a phase II randomized trial with 48 patients.
Most of the efficacy measures ran out to 12 weeks, but researchers followed one measure, the American College of Rheumatology N (ACR-N) index of improvement, out to 39 weeks after a single infusion, and this measure showed a statistically significant, durable benefit from the higher tested dose of mesenchymal precursor cells (MPC) when compared with placebo, Suzanne Kafaja, MD, said while presenting a poster at the European Congress of Rheumatology.
“The trial met its primary endpoints, and so far the data look pretty encouraging, but it’s still pretty early,” she said.
“I was surprised by the durability” of the anti-inflammatory effect of the MPC at 39 weeks, Dr. Kafaja added in an interview.
The study, run at 16 U.S. centers and 2 sites in Australia, enrolled 48 patients with rheumatoid arthritis and on a stable methotrexate regimen for at least 4 months who had a history of failing to adequately respond to at least one biological disease-modifying drug, most commonly a tumor necrosis factor inhibitor. The average age of the enrolled patients was 55 years; nearly three-quarters were women. The patients had been diagnosed with rheumatoid arthritis for an average of 13 years, and more than one-third of the patients had a history of inadequate response to three or more biological agents.
Thirty-six of the patients received a single infusion of a preparation of MPC taken from the bone marrow of healthy donors and isolated and expanded ex vivo. Half the patients in the active-treatment group received 1 million MPC per kg, and the other half received 2 million MPC per kg. An additional 16 patients received placebo. The researchers obtained the MPC from Mesoblast Limited, an Australia-based company that sponsored the study and uses a proprietary method for MPC processing to produce an “off-the-shelf” product.
The allogeneic MPC used in the study is a homogeneous population of cells that respond to pro-inflammatory cytokines by releasing cytokines of their own that induce monocytes and T-cells into an anti-inflammatory state.
The treatment groups showed no difference, compared with the placebo group, for the ACR20, ACR50, and ACR70 measurements, but for two other measures, the Health Assessment Questionnaire and the 28-joint Disease Activity Score, the results showed trends toward dose-related improvements following MPC treatment. The results showed statistically significant improvements after 12 and 39 weeks in average ACR-N in the patients who received 2 million MPC per kg. After 39 weeks, the average ACR-N improvement rate was about 35% among patients who had received 2 million MPC per kg, about 10% among those who received 1 million cells per kg, and about 8% among placebo patients, Dr. Kafaja reported.
Mesoblast funded the study. Dr. Kafaja had no other disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – A single injection of allogeneic mesenchymal precursor cells was apparently both safe and effective for relieving some symptoms of rheumatoid arthritis in biological-refractory patients in a phase II randomized trial with 48 patients.
Most of the efficacy measures ran out to 12 weeks, but researchers followed one measure, the American College of Rheumatology N (ACR-N) index of improvement, out to 39 weeks after a single infusion, and this measure showed a statistically significant, durable benefit from the higher tested dose of mesenchymal precursor cells (MPC) when compared with placebo, Suzanne Kafaja, MD, said while presenting a poster at the European Congress of Rheumatology.
“The trial met its primary endpoints, and so far the data look pretty encouraging, but it’s still pretty early,” she said.
“I was surprised by the durability” of the anti-inflammatory effect of the MPC at 39 weeks, Dr. Kafaja added in an interview.
The study, run at 16 U.S. centers and 2 sites in Australia, enrolled 48 patients with rheumatoid arthritis and on a stable methotrexate regimen for at least 4 months who had a history of failing to adequately respond to at least one biological disease-modifying drug, most commonly a tumor necrosis factor inhibitor. The average age of the enrolled patients was 55 years; nearly three-quarters were women. The patients had been diagnosed with rheumatoid arthritis for an average of 13 years, and more than one-third of the patients had a history of inadequate response to three or more biological agents.
Thirty-six of the patients received a single infusion of a preparation of MPC taken from the bone marrow of healthy donors and isolated and expanded ex vivo. Half the patients in the active-treatment group received 1 million MPC per kg, and the other half received 2 million MPC per kg. An additional 16 patients received placebo. The researchers obtained the MPC from Mesoblast Limited, an Australia-based company that sponsored the study and uses a proprietary method for MPC processing to produce an “off-the-shelf” product.
The allogeneic MPC used in the study is a homogeneous population of cells that respond to pro-inflammatory cytokines by releasing cytokines of their own that induce monocytes and T-cells into an anti-inflammatory state.
The treatment groups showed no difference, compared with the placebo group, for the ACR20, ACR50, and ACR70 measurements, but for two other measures, the Health Assessment Questionnaire and the 28-joint Disease Activity Score, the results showed trends toward dose-related improvements following MPC treatment. The results showed statistically significant improvements after 12 and 39 weeks in average ACR-N in the patients who received 2 million MPC per kg. After 39 weeks, the average ACR-N improvement rate was about 35% among patients who had received 2 million MPC per kg, about 10% among those who received 1 million cells per kg, and about 8% among placebo patients, Dr. Kafaja reported.
Mesoblast funded the study. Dr. Kafaja had no other disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Mesenchymal precursor cells led to an average 35% ACR-N improvement, compared with 8% in placebo-treated patients.
Data source: A multicenter, dose-ranging phase II study with 48 rheumatoid arthritis patients.
Disclosures: Mesoblast funded the study. Dr. Kafaja had no other disclosures.
Panel revises spondyloarthritis treat-to-target recommendations
MADRID – The newly revised recommendations from an unaffiliated, international expert panel on a treat-to-target approach for axial spondyloarthritis and psoriatic arthritis has one conspicuous feature that the prior recommendations lacked: evidence.
The first treat-to-target recommendations for spondyloarthritis (SpA) and psoriatic arthritis (PsA) from 2013 were based entirely on expert opinion (Ann Rheum Dis. 2014 Jan;73[1]:6-16), but in the new update 4 of the 11 recommendations now have an evidence base as well as a fifth recommendation for the part that pertains to PsA, Désirée van der Heijde, MD, said at the European Congress of Rheumatology.
Among the evidence-based recommendations, the most striking was a new formulation for how to measure disease activity. The new recommendations call the ASDAS (Ankylosing Spondylitis Disease Activity Score) the “preferred” disease activity measure for patients with axial SpA and cite both the DAPSA (Disease Activity Index for Psoriatic Arthritis) as well as minimal disease activity as “considered to define the target” when treating PsA.
“This recommendation just made it,” squeaking onto the list with a 52% vote of approval from the task force members, said Dr. van der Heijde. “It had the longest discussion,” with a significant minority of panelists taking a different view.
ASDAS shook out as the preferred measure for axial SpA because of evidence linking a patient’s ASDAS with syndesmophyte formation. “The idea is that by targeting ASDAS you should have better outcomes,” she explained.
“Applying a treat-to-target approach in axial SpA is feasible but requires systematic collection of outcome parameters in daily practice,” such as ASDAS, said Dr. Dougados, professor of rheumatology at Cochin Hospital in Paris. Another piece currently lacking in the case for treat-to-target is demonstration of the clinical benefit from this approach in a trial, he added.
According to Dr. van der Heijde, the other four recommendations that now have evidence backup are:
- Define clinical remission or minimal disease as the absence of clinical and laboratory evidence of significant disease activity.
- An alternative treatment target for PsA may be low or minimal disease activity.
- Measure disease activity by clinical signs and symptoms and by acute phase reactants.
- Once a treatment target is reached it should be maintained.
The task force also outlined “an extensive research agenda” where evidence is needed, specifying close to 50 individual research topics. Among them Dr. van der Heijde particularly called out the role of the Health Assessment Questionnaire (HAQ), validation of PsA target outcomes, and better parsing of the differences using remission or low disease activity as the treatment target.
Dr. van der Heijde, Dr. Dougados, and Dr. Braun are all consultants for several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The evidence we now have is the difference between the new recommendations and the prior version. We have evidence from trials in patients with psoriatic arthritis using minimal disease activity as a target. And we have indirect evidence from observational studies in patients with SpA that suggest the higher the ASDAS, the more progression occurs. In addition, results reported at the EULAR 2017 Congress showed that reductions in the ASDAS appeared to correlate with the effect of a tumor necrosis factor inhibitor on reduced radiographic progression in patients with ankylosing spondylitis. But this is just an association; data from a randomized, prospective trial should be available next year.
The recommendations say to manage patients with axial SpA or psoriatic arthritis by treating them to a target. To do that a clinician needs a standardized assessment of a patient’s disease and to perform follow-up measurements to see if the target is met. The data Dr. Dougados cited from Paris document that assessments such as an ASDAS are rarely made. Getting an ASDAS means knowing either a patient’s C-reactive protein level or erythrocyte sedimentation rate. That requires blood work before a clinic visit, something patients often don’t want.
Will these recommendations change practice and make the ASDAS more widely used? That depends to some extent on whether any benefits or penalties linked to ASDAS use go into place.
Next year, we expect to see results from trials that are testing whether the treat-to-target approach produces better outcomes. Evidence like that will be important to further spur adoption.
Lianne S. Gensler, MD , is director of the ankylosing spondylitis clinic at the University of California, San Francisco. She has been a consultant to Novartis and Janssen and has received research support from AbbVie and UCB. Dr. Gensler was a member of the task force that issued the revised recommendations. She made these comments in an interview.
The evidence we now have is the difference between the new recommendations and the prior version. We have evidence from trials in patients with psoriatic arthritis using minimal disease activity as a target. And we have indirect evidence from observational studies in patients with SpA that suggest the higher the ASDAS, the more progression occurs. In addition, results reported at the EULAR 2017 Congress showed that reductions in the ASDAS appeared to correlate with the effect of a tumor necrosis factor inhibitor on reduced radiographic progression in patients with ankylosing spondylitis. But this is just an association; data from a randomized, prospective trial should be available next year.
The recommendations say to manage patients with axial SpA or psoriatic arthritis by treating them to a target. To do that a clinician needs a standardized assessment of a patient’s disease and to perform follow-up measurements to see if the target is met. The data Dr. Dougados cited from Paris document that assessments such as an ASDAS are rarely made. Getting an ASDAS means knowing either a patient’s C-reactive protein level or erythrocyte sedimentation rate. That requires blood work before a clinic visit, something patients often don’t want.
Will these recommendations change practice and make the ASDAS more widely used? That depends to some extent on whether any benefits or penalties linked to ASDAS use go into place.
Next year, we expect to see results from trials that are testing whether the treat-to-target approach produces better outcomes. Evidence like that will be important to further spur adoption.
Lianne S. Gensler, MD , is director of the ankylosing spondylitis clinic at the University of California, San Francisco. She has been a consultant to Novartis and Janssen and has received research support from AbbVie and UCB. Dr. Gensler was a member of the task force that issued the revised recommendations. She made these comments in an interview.
The evidence we now have is the difference between the new recommendations and the prior version. We have evidence from trials in patients with psoriatic arthritis using minimal disease activity as a target. And we have indirect evidence from observational studies in patients with SpA that suggest the higher the ASDAS, the more progression occurs. In addition, results reported at the EULAR 2017 Congress showed that reductions in the ASDAS appeared to correlate with the effect of a tumor necrosis factor inhibitor on reduced radiographic progression in patients with ankylosing spondylitis. But this is just an association; data from a randomized, prospective trial should be available next year.
The recommendations say to manage patients with axial SpA or psoriatic arthritis by treating them to a target. To do that a clinician needs a standardized assessment of a patient’s disease and to perform follow-up measurements to see if the target is met. The data Dr. Dougados cited from Paris document that assessments such as an ASDAS are rarely made. Getting an ASDAS means knowing either a patient’s C-reactive protein level or erythrocyte sedimentation rate. That requires blood work before a clinic visit, something patients often don’t want.
Will these recommendations change practice and make the ASDAS more widely used? That depends to some extent on whether any benefits or penalties linked to ASDAS use go into place.
Next year, we expect to see results from trials that are testing whether the treat-to-target approach produces better outcomes. Evidence like that will be important to further spur adoption.
Lianne S. Gensler, MD , is director of the ankylosing spondylitis clinic at the University of California, San Francisco. She has been a consultant to Novartis and Janssen and has received research support from AbbVie and UCB. Dr. Gensler was a member of the task force that issued the revised recommendations. She made these comments in an interview.
MADRID – The newly revised recommendations from an unaffiliated, international expert panel on a treat-to-target approach for axial spondyloarthritis and psoriatic arthritis has one conspicuous feature that the prior recommendations lacked: evidence.
The first treat-to-target recommendations for spondyloarthritis (SpA) and psoriatic arthritis (PsA) from 2013 were based entirely on expert opinion (Ann Rheum Dis. 2014 Jan;73[1]:6-16), but in the new update 4 of the 11 recommendations now have an evidence base as well as a fifth recommendation for the part that pertains to PsA, Désirée van der Heijde, MD, said at the European Congress of Rheumatology.
Among the evidence-based recommendations, the most striking was a new formulation for how to measure disease activity. The new recommendations call the ASDAS (Ankylosing Spondylitis Disease Activity Score) the “preferred” disease activity measure for patients with axial SpA and cite both the DAPSA (Disease Activity Index for Psoriatic Arthritis) as well as minimal disease activity as “considered to define the target” when treating PsA.
“This recommendation just made it,” squeaking onto the list with a 52% vote of approval from the task force members, said Dr. van der Heijde. “It had the longest discussion,” with a significant minority of panelists taking a different view.
ASDAS shook out as the preferred measure for axial SpA because of evidence linking a patient’s ASDAS with syndesmophyte formation. “The idea is that by targeting ASDAS you should have better outcomes,” she explained.
“Applying a treat-to-target approach in axial SpA is feasible but requires systematic collection of outcome parameters in daily practice,” such as ASDAS, said Dr. Dougados, professor of rheumatology at Cochin Hospital in Paris. Another piece currently lacking in the case for treat-to-target is demonstration of the clinical benefit from this approach in a trial, he added.
According to Dr. van der Heijde, the other four recommendations that now have evidence backup are:
- Define clinical remission or minimal disease as the absence of clinical and laboratory evidence of significant disease activity.
- An alternative treatment target for PsA may be low or minimal disease activity.
- Measure disease activity by clinical signs and symptoms and by acute phase reactants.
- Once a treatment target is reached it should be maintained.
The task force also outlined “an extensive research agenda” where evidence is needed, specifying close to 50 individual research topics. Among them Dr. van der Heijde particularly called out the role of the Health Assessment Questionnaire (HAQ), validation of PsA target outcomes, and better parsing of the differences using remission or low disease activity as the treatment target.
Dr. van der Heijde, Dr. Dougados, and Dr. Braun are all consultants for several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
MADRID – The newly revised recommendations from an unaffiliated, international expert panel on a treat-to-target approach for axial spondyloarthritis and psoriatic arthritis has one conspicuous feature that the prior recommendations lacked: evidence.
The first treat-to-target recommendations for spondyloarthritis (SpA) and psoriatic arthritis (PsA) from 2013 were based entirely on expert opinion (Ann Rheum Dis. 2014 Jan;73[1]:6-16), but in the new update 4 of the 11 recommendations now have an evidence base as well as a fifth recommendation for the part that pertains to PsA, Désirée van der Heijde, MD, said at the European Congress of Rheumatology.
Among the evidence-based recommendations, the most striking was a new formulation for how to measure disease activity. The new recommendations call the ASDAS (Ankylosing Spondylitis Disease Activity Score) the “preferred” disease activity measure for patients with axial SpA and cite both the DAPSA (Disease Activity Index for Psoriatic Arthritis) as well as minimal disease activity as “considered to define the target” when treating PsA.
“This recommendation just made it,” squeaking onto the list with a 52% vote of approval from the task force members, said Dr. van der Heijde. “It had the longest discussion,” with a significant minority of panelists taking a different view.
ASDAS shook out as the preferred measure for axial SpA because of evidence linking a patient’s ASDAS with syndesmophyte formation. “The idea is that by targeting ASDAS you should have better outcomes,” she explained.
“Applying a treat-to-target approach in axial SpA is feasible but requires systematic collection of outcome parameters in daily practice,” such as ASDAS, said Dr. Dougados, professor of rheumatology at Cochin Hospital in Paris. Another piece currently lacking in the case for treat-to-target is demonstration of the clinical benefit from this approach in a trial, he added.
According to Dr. van der Heijde, the other four recommendations that now have evidence backup are:
- Define clinical remission or minimal disease as the absence of clinical and laboratory evidence of significant disease activity.
- An alternative treatment target for PsA may be low or minimal disease activity.
- Measure disease activity by clinical signs and symptoms and by acute phase reactants.
- Once a treatment target is reached it should be maintained.
The task force also outlined “an extensive research agenda” where evidence is needed, specifying close to 50 individual research topics. Among them Dr. van der Heijde particularly called out the role of the Health Assessment Questionnaire (HAQ), validation of PsA target outcomes, and better parsing of the differences using remission or low disease activity as the treatment target.
Dr. van der Heijde, Dr. Dougados, and Dr. Braun are all consultants for several drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE EULAR 2017 CONGRESS
Rest dyspnea dims as acute heart failure treatment target
PARIS – During the most recent pharmaceutical generation, drug development for heart failure largely focused on acute heart failure, and specifically on patients with rest dyspnea as the primary manifestation of their acute heart failure decompensation events.
That has now changed, agreed heart failure experts as they debated the upshot of sobering results from two neutral trials that failed to show a midterm mortality benefit in patients hospitalized for acute heart failure who underwent aggressive management of their congestion using 2 days of intravenous treatment with either of two potent vasodilating drugs. Results first reported in November 2016 failed to show a survival benefit from ularitide in the 2,100-patient TRUE-AHF (Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure) trial (N Engl J Med. 2017 May 18;376[20]:1956-64). And results reported at a meeting of the Heart Failure Association of the ESC failed to show a survival benefit from serelaxin in more than 6,500 acute heart failure patients in the RELAX-AHF-2 (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF) trial.
The failure of a 2-day infusion of serelaxin to produce a significant reduction in cardiovascular death in RELAX-AHF-2 was especially surprising because the predecessor trial, RELAX-AHF, which randomized only 1,160 patients and used a surrogate endpoint of dyspnea improvement, had shown significant benefit that hinted more clinically meaningful benefits might also result from serelaxin treatment (Lancet. 2013 Jan 5;381[9860]:29-39). The disappointing serelaxin and ularitide results also culminate a series of studies using several different agents or procedures to treat acute decompensated heart failure patients that all failed to produce a reduction in deaths.
“This is a sea change; make no mistake. We will need a more targeted, selective approach. It was always a daunting proposition to believe that short-term infusion could have an effect 6 months later. We were misled by the analogy [of acute heart failure] to acute coronary syndrome,” said Dr. Ruschitzka, professor of medicine at the University of Zürich.
The right time to intervene
Meeting attendees offered several hypotheses to explain why the acute ularitide and serelaxin trials both failed to show a mortality benefit, with timing of treatment the most common denominator.
Acute heart failure “is an event, not a disease,” declared Milton Packer, MD, lead investigator of TRUE-AHF, during a session devoted to vasodilator treatment of acute heart failure. Acute heart failure decompensations “are fluctuations in a chronic disease. It doesn’t matter what you do during the episode – it matters what you do between acute episodes. We focus all our attention on which vasodilator and which dose of Lasix [furosemide], but we send patients home on inadequate chronic therapy. It doesn’t matter what you do to the dyspnea, the shortness of breath will get better. Do we need a new drug that makes dyspnea go away an hour sooner and doesn’t cost a fortune? What really matters is what patients do between acute episodes and how to prevent them, ” said Dr. Packer, distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
Dr. Packer strongly urged clinicians to put heart failure patients on the full regimen of guideline-directed drugs and at full dosages, a step he thinks would go a long way toward preventing a majority of decompensation episodes. “Chronic heart failure treatment has improved dramatically, but implementation is abysmal,” he said.
Of course, at this phase of their disease heart failure patients are usually at home, which more or less demands that the treatments they take are oral or at least delivered by subcutaneous injection.
“We’ve had a mismatch of candidate drugs, which have mostly been IV infusions, with a clinical setting where an IV infusion is challenging to use.”
“We are killing good drugs by the way we’re testing them,” commented Javed Butler, MD, who bemoaned the ignominious outcome of serelaxin treatment in RELAX-AHF-2. “The available data show it makes no sense to treat for just 2 days. We should take true worsening heart failure patients, those who are truly failing standard treatment, and look at new chronic oral therapies to try on them.” Oral drugs similar to serelaxin and ularitide could be used chronically, suggested Dr. Butler, professor of medicine and chief of cardiology at Stony Brook (N.Y.) School of Medicine.
Wrong patients with the wrong presentation
Perhaps just as big a flaw of the acute heart failure trials has been their target patient population, patients with rest dyspnea at the time of admission. “Why do we think that dyspnea is a clinically relevant symptom for acute heart failure?” Dr. Packer asked.
Dr. Cleland and his associates analyzed data on 116,752 hospitalizations for acute heart failure in England and Wales during April 2007–March 2013, a database that included more than 90% of hospitals for these regions. “We found that a large proportion of admitted patients did not have breathlessness at rest as their primary reason for seeking hospitalization. For about half the patients, moderate or severe peripheral edema was the main problem,” he reported. Roughly a third of patients had rest dyspnea as their main symptom.
An unadjusted analysis also showed a stronger link between peripheral edema and the rate of mortality during a median follow-up of about a year following hospitalization, compared with rest dyspnea. Compared with the lowest-risk subgroup, the patients with severe peripheral edema (18% of the population) had more than twice the mortality. In contrast, the patients with the most severe rest dyspnea and no evidence at all of peripheral edema, just 6% of the population, had a 50% higher mortality rate than the lowest-risk patients.
”It’s peripheral edema rather than breathlessness that is the important determinant of length of stay and prognosis. The disastrous neutral trials for acute heart failure have all targeted the breathless subset of patients. Maybe a reason for the failures has been that they’ve been treating a problem that does not exist. The trials have looked at the wrong patients,” Dr. Cleland said.
‘We’ve told the wrong story to industry” about the importance of rest dyspnea to acute heart failure patients. “When we say acute heart failure, we mean an ambulance and oxygen and the emergency department and rapid IV treatment. That’s breathlessness. Patients with peripheral edema usually get driven in and walk from the car to a wheelchair and they wait 4 hours to be seen. I think that, following the TRUE-AHF and RELAX-AHF-2 results, we’ll see a radical change.”
But just because the focus should be on peripheral edema rather than dyspnea, that doesn’t mean better drugs aren’t needed, Dr. Cleland added.
“We need better treatments to deal with congestion. Once a patient is congested, we are not very good at getting rid of it. We depend on diuretics, which we don’t use properly. Ultimately I’d like to see agents as adjuncts to diuretics, to produce better kidney function.” But treatments for breathlessness are decent as they now exist: furosemide plus oxygen. When a simple, cheap drug works 80% of the time, it is really hard to improve on that.” The real unmet needs for treating acute decompensated heart failure are patients with rest dyspnea who don’t respond to conventional treatment, and especially patients with gross peripheral edema plus low blood pressure and renal dysfunction for whom no good treatments have been developed, Dr. Cleland said.
Another flaw in the patient selection criteria for the acute heart failure studies has been the focus on patients with elevated blood pressures, the logical target for vasodilator drugs that lower blood pressure, noted Dr. Felker. “But these are the patients at lowest risk. We’ve had a mismatch between the patients with the biggest need and the patients we actually study, which relates to the types of drugs we’ve developed.”
Acute heart failure remains a target
Despite all the talk of refocusing attention on chronic heart failure and peripheral edema, at least one expert remained steadfast in talking up the importance of new acute interventions.
Part of the problem in believing that existing treatments can adequately manage heart failure and prevent acute decompensations is that about 75% of acute heart failure episodes either occur as the first presentation of heart failure, or occur in patients with heart failure with preserved ejection fraction (HFpEF), a type of heart failure that, until recently, had no chronic drug regimens with widely acknowledged efficacy for HFpEF. (The 2017 U.S. heart failure management guidelines update listed aldosterone receptor antagonists as a class IIb recommendation for treating HFpEF, the first time guidelines have sanctioned a drug class for treating HFpEF [Circulation. 2017 Apr 28. doi: 10.1161/CIR.0000000000000509].)
“For patients with heart failure with reduced ejection fraction, you can give optimal treatments and [decompensations] are prevented,” noted Dr. Mebazaa, a professor of anesthesiology and resuscitation at Lariboisière Hospital in Paris. “But for the huge number of HFpEF patients we have nothing. Acute heart failure will remain prevalent, and we still don’t have the right drugs to use on these patients.”
The TRUE-AHF trial was sponsored by Cardiorentis. RELAX-AHF-2 was sponsored by Novartis. Dr. Ruschitzka has been a speaker on behalf of Novartis, and has been a speaker for or consultant to several companies and was a coinvestigator for TRUE-AHF and received fees from Cardiorentis for his participation. Dr. Packer is a consultant to and stockholder in Cardiorentis and has been a consultant to several other companies. Dr. Felker has been a consultant to Novartis and several other companies and was a coinvestigator on RELAX-AHF-2. Dr. Butler has been a consultant to several companies. Dr. Cleland has received research support from Novartis, and he has been a consultant to and received research support from several other companies. Dr. Mebazaa has received honoraria from Novartis and Cardiorentis as well as from several other companies and was a coinvestigator on TRUE-AHF.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – During the most recent pharmaceutical generation, drug development for heart failure largely focused on acute heart failure, and specifically on patients with rest dyspnea as the primary manifestation of their acute heart failure decompensation events.
That has now changed, agreed heart failure experts as they debated the upshot of sobering results from two neutral trials that failed to show a midterm mortality benefit in patients hospitalized for acute heart failure who underwent aggressive management of their congestion using 2 days of intravenous treatment with either of two potent vasodilating drugs. Results first reported in November 2016 failed to show a survival benefit from ularitide in the 2,100-patient TRUE-AHF (Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure) trial (N Engl J Med. 2017 May 18;376[20]:1956-64). And results reported at a meeting of the Heart Failure Association of the ESC failed to show a survival benefit from serelaxin in more than 6,500 acute heart failure patients in the RELAX-AHF-2 (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF) trial.
The failure of a 2-day infusion of serelaxin to produce a significant reduction in cardiovascular death in RELAX-AHF-2 was especially surprising because the predecessor trial, RELAX-AHF, which randomized only 1,160 patients and used a surrogate endpoint of dyspnea improvement, had shown significant benefit that hinted more clinically meaningful benefits might also result from serelaxin treatment (Lancet. 2013 Jan 5;381[9860]:29-39). The disappointing serelaxin and ularitide results also culminate a series of studies using several different agents or procedures to treat acute decompensated heart failure patients that all failed to produce a reduction in deaths.
“This is a sea change; make no mistake. We will need a more targeted, selective approach. It was always a daunting proposition to believe that short-term infusion could have an effect 6 months later. We were misled by the analogy [of acute heart failure] to acute coronary syndrome,” said Dr. Ruschitzka, professor of medicine at the University of Zürich.
The right time to intervene
Meeting attendees offered several hypotheses to explain why the acute ularitide and serelaxin trials both failed to show a mortality benefit, with timing of treatment the most common denominator.
Acute heart failure “is an event, not a disease,” declared Milton Packer, MD, lead investigator of TRUE-AHF, during a session devoted to vasodilator treatment of acute heart failure. Acute heart failure decompensations “are fluctuations in a chronic disease. It doesn’t matter what you do during the episode – it matters what you do between acute episodes. We focus all our attention on which vasodilator and which dose of Lasix [furosemide], but we send patients home on inadequate chronic therapy. It doesn’t matter what you do to the dyspnea, the shortness of breath will get better. Do we need a new drug that makes dyspnea go away an hour sooner and doesn’t cost a fortune? What really matters is what patients do between acute episodes and how to prevent them, ” said Dr. Packer, distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
Dr. Packer strongly urged clinicians to put heart failure patients on the full regimen of guideline-directed drugs and at full dosages, a step he thinks would go a long way toward preventing a majority of decompensation episodes. “Chronic heart failure treatment has improved dramatically, but implementation is abysmal,” he said.
Of course, at this phase of their disease heart failure patients are usually at home, which more or less demands that the treatments they take are oral or at least delivered by subcutaneous injection.
“We’ve had a mismatch of candidate drugs, which have mostly been IV infusions, with a clinical setting where an IV infusion is challenging to use.”
“We are killing good drugs by the way we’re testing them,” commented Javed Butler, MD, who bemoaned the ignominious outcome of serelaxin treatment in RELAX-AHF-2. “The available data show it makes no sense to treat for just 2 days. We should take true worsening heart failure patients, those who are truly failing standard treatment, and look at new chronic oral therapies to try on them.” Oral drugs similar to serelaxin and ularitide could be used chronically, suggested Dr. Butler, professor of medicine and chief of cardiology at Stony Brook (N.Y.) School of Medicine.
Wrong patients with the wrong presentation
Perhaps just as big a flaw of the acute heart failure trials has been their target patient population, patients with rest dyspnea at the time of admission. “Why do we think that dyspnea is a clinically relevant symptom for acute heart failure?” Dr. Packer asked.
Dr. Cleland and his associates analyzed data on 116,752 hospitalizations for acute heart failure in England and Wales during April 2007–March 2013, a database that included more than 90% of hospitals for these regions. “We found that a large proportion of admitted patients did not have breathlessness at rest as their primary reason for seeking hospitalization. For about half the patients, moderate or severe peripheral edema was the main problem,” he reported. Roughly a third of patients had rest dyspnea as their main symptom.
An unadjusted analysis also showed a stronger link between peripheral edema and the rate of mortality during a median follow-up of about a year following hospitalization, compared with rest dyspnea. Compared with the lowest-risk subgroup, the patients with severe peripheral edema (18% of the population) had more than twice the mortality. In contrast, the patients with the most severe rest dyspnea and no evidence at all of peripheral edema, just 6% of the population, had a 50% higher mortality rate than the lowest-risk patients.
”It’s peripheral edema rather than breathlessness that is the important determinant of length of stay and prognosis. The disastrous neutral trials for acute heart failure have all targeted the breathless subset of patients. Maybe a reason for the failures has been that they’ve been treating a problem that does not exist. The trials have looked at the wrong patients,” Dr. Cleland said.
‘We’ve told the wrong story to industry” about the importance of rest dyspnea to acute heart failure patients. “When we say acute heart failure, we mean an ambulance and oxygen and the emergency department and rapid IV treatment. That’s breathlessness. Patients with peripheral edema usually get driven in and walk from the car to a wheelchair and they wait 4 hours to be seen. I think that, following the TRUE-AHF and RELAX-AHF-2 results, we’ll see a radical change.”
But just because the focus should be on peripheral edema rather than dyspnea, that doesn’t mean better drugs aren’t needed, Dr. Cleland added.
“We need better treatments to deal with congestion. Once a patient is congested, we are not very good at getting rid of it. We depend on diuretics, which we don’t use properly. Ultimately I’d like to see agents as adjuncts to diuretics, to produce better kidney function.” But treatments for breathlessness are decent as they now exist: furosemide plus oxygen. When a simple, cheap drug works 80% of the time, it is really hard to improve on that.” The real unmet needs for treating acute decompensated heart failure are patients with rest dyspnea who don’t respond to conventional treatment, and especially patients with gross peripheral edema plus low blood pressure and renal dysfunction for whom no good treatments have been developed, Dr. Cleland said.
Another flaw in the patient selection criteria for the acute heart failure studies has been the focus on patients with elevated blood pressures, the logical target for vasodilator drugs that lower blood pressure, noted Dr. Felker. “But these are the patients at lowest risk. We’ve had a mismatch between the patients with the biggest need and the patients we actually study, which relates to the types of drugs we’ve developed.”
Acute heart failure remains a target
Despite all the talk of refocusing attention on chronic heart failure and peripheral edema, at least one expert remained steadfast in talking up the importance of new acute interventions.
Part of the problem in believing that existing treatments can adequately manage heart failure and prevent acute decompensations is that about 75% of acute heart failure episodes either occur as the first presentation of heart failure, or occur in patients with heart failure with preserved ejection fraction (HFpEF), a type of heart failure that, until recently, had no chronic drug regimens with widely acknowledged efficacy for HFpEF. (The 2017 U.S. heart failure management guidelines update listed aldosterone receptor antagonists as a class IIb recommendation for treating HFpEF, the first time guidelines have sanctioned a drug class for treating HFpEF [Circulation. 2017 Apr 28. doi: 10.1161/CIR.0000000000000509].)
“For patients with heart failure with reduced ejection fraction, you can give optimal treatments and [decompensations] are prevented,” noted Dr. Mebazaa, a professor of anesthesiology and resuscitation at Lariboisière Hospital in Paris. “But for the huge number of HFpEF patients we have nothing. Acute heart failure will remain prevalent, and we still don’t have the right drugs to use on these patients.”
The TRUE-AHF trial was sponsored by Cardiorentis. RELAX-AHF-2 was sponsored by Novartis. Dr. Ruschitzka has been a speaker on behalf of Novartis, and has been a speaker for or consultant to several companies and was a coinvestigator for TRUE-AHF and received fees from Cardiorentis for his participation. Dr. Packer is a consultant to and stockholder in Cardiorentis and has been a consultant to several other companies. Dr. Felker has been a consultant to Novartis and several other companies and was a coinvestigator on RELAX-AHF-2. Dr. Butler has been a consultant to several companies. Dr. Cleland has received research support from Novartis, and he has been a consultant to and received research support from several other companies. Dr. Mebazaa has received honoraria from Novartis and Cardiorentis as well as from several other companies and was a coinvestigator on TRUE-AHF.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – During the most recent pharmaceutical generation, drug development for heart failure largely focused on acute heart failure, and specifically on patients with rest dyspnea as the primary manifestation of their acute heart failure decompensation events.
That has now changed, agreed heart failure experts as they debated the upshot of sobering results from two neutral trials that failed to show a midterm mortality benefit in patients hospitalized for acute heart failure who underwent aggressive management of their congestion using 2 days of intravenous treatment with either of two potent vasodilating drugs. Results first reported in November 2016 failed to show a survival benefit from ularitide in the 2,100-patient TRUE-AHF (Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure) trial (N Engl J Med. 2017 May 18;376[20]:1956-64). And results reported at a meeting of the Heart Failure Association of the ESC failed to show a survival benefit from serelaxin in more than 6,500 acute heart failure patients in the RELAX-AHF-2 (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF) trial.
The failure of a 2-day infusion of serelaxin to produce a significant reduction in cardiovascular death in RELAX-AHF-2 was especially surprising because the predecessor trial, RELAX-AHF, which randomized only 1,160 patients and used a surrogate endpoint of dyspnea improvement, had shown significant benefit that hinted more clinically meaningful benefits might also result from serelaxin treatment (Lancet. 2013 Jan 5;381[9860]:29-39). The disappointing serelaxin and ularitide results also culminate a series of studies using several different agents or procedures to treat acute decompensated heart failure patients that all failed to produce a reduction in deaths.
“This is a sea change; make no mistake. We will need a more targeted, selective approach. It was always a daunting proposition to believe that short-term infusion could have an effect 6 months later. We were misled by the analogy [of acute heart failure] to acute coronary syndrome,” said Dr. Ruschitzka, professor of medicine at the University of Zürich.
The right time to intervene
Meeting attendees offered several hypotheses to explain why the acute ularitide and serelaxin trials both failed to show a mortality benefit, with timing of treatment the most common denominator.
Acute heart failure “is an event, not a disease,” declared Milton Packer, MD, lead investigator of TRUE-AHF, during a session devoted to vasodilator treatment of acute heart failure. Acute heart failure decompensations “are fluctuations in a chronic disease. It doesn’t matter what you do during the episode – it matters what you do between acute episodes. We focus all our attention on which vasodilator and which dose of Lasix [furosemide], but we send patients home on inadequate chronic therapy. It doesn’t matter what you do to the dyspnea, the shortness of breath will get better. Do we need a new drug that makes dyspnea go away an hour sooner and doesn’t cost a fortune? What really matters is what patients do between acute episodes and how to prevent them, ” said Dr. Packer, distinguished scholar in cardiovascular science at Baylor University Medical Center in Dallas.
Dr. Packer strongly urged clinicians to put heart failure patients on the full regimen of guideline-directed drugs and at full dosages, a step he thinks would go a long way toward preventing a majority of decompensation episodes. “Chronic heart failure treatment has improved dramatically, but implementation is abysmal,” he said.
Of course, at this phase of their disease heart failure patients are usually at home, which more or less demands that the treatments they take are oral or at least delivered by subcutaneous injection.
“We’ve had a mismatch of candidate drugs, which have mostly been IV infusions, with a clinical setting where an IV infusion is challenging to use.”
“We are killing good drugs by the way we’re testing them,” commented Javed Butler, MD, who bemoaned the ignominious outcome of serelaxin treatment in RELAX-AHF-2. “The available data show it makes no sense to treat for just 2 days. We should take true worsening heart failure patients, those who are truly failing standard treatment, and look at new chronic oral therapies to try on them.” Oral drugs similar to serelaxin and ularitide could be used chronically, suggested Dr. Butler, professor of medicine and chief of cardiology at Stony Brook (N.Y.) School of Medicine.
Wrong patients with the wrong presentation
Perhaps just as big a flaw of the acute heart failure trials has been their target patient population, patients with rest dyspnea at the time of admission. “Why do we think that dyspnea is a clinically relevant symptom for acute heart failure?” Dr. Packer asked.
Dr. Cleland and his associates analyzed data on 116,752 hospitalizations for acute heart failure in England and Wales during April 2007–March 2013, a database that included more than 90% of hospitals for these regions. “We found that a large proportion of admitted patients did not have breathlessness at rest as their primary reason for seeking hospitalization. For about half the patients, moderate or severe peripheral edema was the main problem,” he reported. Roughly a third of patients had rest dyspnea as their main symptom.
An unadjusted analysis also showed a stronger link between peripheral edema and the rate of mortality during a median follow-up of about a year following hospitalization, compared with rest dyspnea. Compared with the lowest-risk subgroup, the patients with severe peripheral edema (18% of the population) had more than twice the mortality. In contrast, the patients with the most severe rest dyspnea and no evidence at all of peripheral edema, just 6% of the population, had a 50% higher mortality rate than the lowest-risk patients.
”It’s peripheral edema rather than breathlessness that is the important determinant of length of stay and prognosis. The disastrous neutral trials for acute heart failure have all targeted the breathless subset of patients. Maybe a reason for the failures has been that they’ve been treating a problem that does not exist. The trials have looked at the wrong patients,” Dr. Cleland said.
‘We’ve told the wrong story to industry” about the importance of rest dyspnea to acute heart failure patients. “When we say acute heart failure, we mean an ambulance and oxygen and the emergency department and rapid IV treatment. That’s breathlessness. Patients with peripheral edema usually get driven in and walk from the car to a wheelchair and they wait 4 hours to be seen. I think that, following the TRUE-AHF and RELAX-AHF-2 results, we’ll see a radical change.”
But just because the focus should be on peripheral edema rather than dyspnea, that doesn’t mean better drugs aren’t needed, Dr. Cleland added.
“We need better treatments to deal with congestion. Once a patient is congested, we are not very good at getting rid of it. We depend on diuretics, which we don’t use properly. Ultimately I’d like to see agents as adjuncts to diuretics, to produce better kidney function.” But treatments for breathlessness are decent as they now exist: furosemide plus oxygen. When a simple, cheap drug works 80% of the time, it is really hard to improve on that.” The real unmet needs for treating acute decompensated heart failure are patients with rest dyspnea who don’t respond to conventional treatment, and especially patients with gross peripheral edema plus low blood pressure and renal dysfunction for whom no good treatments have been developed, Dr. Cleland said.
Another flaw in the patient selection criteria for the acute heart failure studies has been the focus on patients with elevated blood pressures, the logical target for vasodilator drugs that lower blood pressure, noted Dr. Felker. “But these are the patients at lowest risk. We’ve had a mismatch between the patients with the biggest need and the patients we actually study, which relates to the types of drugs we’ve developed.”
Acute heart failure remains a target
Despite all the talk of refocusing attention on chronic heart failure and peripheral edema, at least one expert remained steadfast in talking up the importance of new acute interventions.
Part of the problem in believing that existing treatments can adequately manage heart failure and prevent acute decompensations is that about 75% of acute heart failure episodes either occur as the first presentation of heart failure, or occur in patients with heart failure with preserved ejection fraction (HFpEF), a type of heart failure that, until recently, had no chronic drug regimens with widely acknowledged efficacy for HFpEF. (The 2017 U.S. heart failure management guidelines update listed aldosterone receptor antagonists as a class IIb recommendation for treating HFpEF, the first time guidelines have sanctioned a drug class for treating HFpEF [Circulation. 2017 Apr 28. doi: 10.1161/CIR.0000000000000509].)
“For patients with heart failure with reduced ejection fraction, you can give optimal treatments and [decompensations] are prevented,” noted Dr. Mebazaa, a professor of anesthesiology and resuscitation at Lariboisière Hospital in Paris. “But for the huge number of HFpEF patients we have nothing. Acute heart failure will remain prevalent, and we still don’t have the right drugs to use on these patients.”
The TRUE-AHF trial was sponsored by Cardiorentis. RELAX-AHF-2 was sponsored by Novartis. Dr. Ruschitzka has been a speaker on behalf of Novartis, and has been a speaker for or consultant to several companies and was a coinvestigator for TRUE-AHF and received fees from Cardiorentis for his participation. Dr. Packer is a consultant to and stockholder in Cardiorentis and has been a consultant to several other companies. Dr. Felker has been a consultant to Novartis and several other companies and was a coinvestigator on RELAX-AHF-2. Dr. Butler has been a consultant to several companies. Dr. Cleland has received research support from Novartis, and he has been a consultant to and received research support from several other companies. Dr. Mebazaa has received honoraria from Novartis and Cardiorentis as well as from several other companies and was a coinvestigator on TRUE-AHF.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM HEART FAILURE 2017
Frequent bronchiectasis exacerbations linked to higher mortality
WASHINGTON – Bronchiectasis patients with three or more exacerbations per year had twice the mortality during 5-year follow-up as patients with no recent exacerbations, in a prospective registry of nearly 2,600 European bronchiectasis patients.
A multivariate analysis showed this statistically significant doubled death rate after adjustment for baseline demographic and clinical differences between patients with no exacerbations during the year before they entered the registry, James D. Chalmers, MD, said at an international conference of the American Thoracic Society.
This 37% prevalence contrasted with a 19% U.S. prevalence of bronchiectasis patients having two or more exacerbations per year among 2,114 patients enrolled in a 13-center U.S. registry that was reported during the same session by Timothy R. Aksamit, MD, a pulmonologist at the Mayo Clinic in Rochester, Minn. During his talk, Dr. Aksamit suggested that the European cohort might include more patients with asthma, chronic obstructive pulmonary disease, or other complications in addition to bronchiectasis. Dr. Aksamit contended that the U.S. registry tried to exclusively enroll patients with bronchiectasis and no other disorder, possibly explaining the prevalence difference between Europe and the United States.
The European registry included patients with bronchiectasis seen in 10 centers in seven European countries and Israel. They averaged 67 years of age. While more than a third had a history of at least three exacerbations a year, one-quarter had no exacerbations during the year before they entered the study.
The U.S. registry reported by Dr. Aksamit had 2-year follow-up data for 1,049 of the enrolled patients, a subgroup that closely matched the entire population initially enrolled. The 2-year follow-up showed an overall average exacerbation rate of 0.75 episodes per year, but this was driven largely by the subgroup of patients who entered the registry with a history of two or more exacerbations per year, who then averaged about 2.6 exacerbations during follow-up. In contrast, patients who entered the registry with a history of fewer than two exacerbations per year averaged fewer than a third of an exacerbation per year during follow-up, Dr. Aksamit reported.
The European bronchiectasis registry was partially funded by Bayer. Dr. Chalmers has been a consultant to Bayer and to AstraZeneca, Basilea, Grifols, Napp, and Raptor and has received research funding from Aradigm, AstraZeneca, Bayer, GlaxoSmithKline, and Pfizer. Dr. Aksamit had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – Bronchiectasis patients with three or more exacerbations per year had twice the mortality during 5-year follow-up as patients with no recent exacerbations, in a prospective registry of nearly 2,600 European bronchiectasis patients.
A multivariate analysis showed this statistically significant doubled death rate after adjustment for baseline demographic and clinical differences between patients with no exacerbations during the year before they entered the registry, James D. Chalmers, MD, said at an international conference of the American Thoracic Society.
This 37% prevalence contrasted with a 19% U.S. prevalence of bronchiectasis patients having two or more exacerbations per year among 2,114 patients enrolled in a 13-center U.S. registry that was reported during the same session by Timothy R. Aksamit, MD, a pulmonologist at the Mayo Clinic in Rochester, Minn. During his talk, Dr. Aksamit suggested that the European cohort might include more patients with asthma, chronic obstructive pulmonary disease, or other complications in addition to bronchiectasis. Dr. Aksamit contended that the U.S. registry tried to exclusively enroll patients with bronchiectasis and no other disorder, possibly explaining the prevalence difference between Europe and the United States.
The European registry included patients with bronchiectasis seen in 10 centers in seven European countries and Israel. They averaged 67 years of age. While more than a third had a history of at least three exacerbations a year, one-quarter had no exacerbations during the year before they entered the study.
The U.S. registry reported by Dr. Aksamit had 2-year follow-up data for 1,049 of the enrolled patients, a subgroup that closely matched the entire population initially enrolled. The 2-year follow-up showed an overall average exacerbation rate of 0.75 episodes per year, but this was driven largely by the subgroup of patients who entered the registry with a history of two or more exacerbations per year, who then averaged about 2.6 exacerbations during follow-up. In contrast, patients who entered the registry with a history of fewer than two exacerbations per year averaged fewer than a third of an exacerbation per year during follow-up, Dr. Aksamit reported.
The European bronchiectasis registry was partially funded by Bayer. Dr. Chalmers has been a consultant to Bayer and to AstraZeneca, Basilea, Grifols, Napp, and Raptor and has received research funding from Aradigm, AstraZeneca, Bayer, GlaxoSmithKline, and Pfizer. Dr. Aksamit had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
WASHINGTON – Bronchiectasis patients with three or more exacerbations per year had twice the mortality during 5-year follow-up as patients with no recent exacerbations, in a prospective registry of nearly 2,600 European bronchiectasis patients.
A multivariate analysis showed this statistically significant doubled death rate after adjustment for baseline demographic and clinical differences between patients with no exacerbations during the year before they entered the registry, James D. Chalmers, MD, said at an international conference of the American Thoracic Society.
This 37% prevalence contrasted with a 19% U.S. prevalence of bronchiectasis patients having two or more exacerbations per year among 2,114 patients enrolled in a 13-center U.S. registry that was reported during the same session by Timothy R. Aksamit, MD, a pulmonologist at the Mayo Clinic in Rochester, Minn. During his talk, Dr. Aksamit suggested that the European cohort might include more patients with asthma, chronic obstructive pulmonary disease, or other complications in addition to bronchiectasis. Dr. Aksamit contended that the U.S. registry tried to exclusively enroll patients with bronchiectasis and no other disorder, possibly explaining the prevalence difference between Europe and the United States.
The European registry included patients with bronchiectasis seen in 10 centers in seven European countries and Israel. They averaged 67 years of age. While more than a third had a history of at least three exacerbations a year, one-quarter had no exacerbations during the year before they entered the study.
The U.S. registry reported by Dr. Aksamit had 2-year follow-up data for 1,049 of the enrolled patients, a subgroup that closely matched the entire population initially enrolled. The 2-year follow-up showed an overall average exacerbation rate of 0.75 episodes per year, but this was driven largely by the subgroup of patients who entered the registry with a history of two or more exacerbations per year, who then averaged about 2.6 exacerbations during follow-up. In contrast, patients who entered the registry with a history of fewer than two exacerbations per year averaged fewer than a third of an exacerbation per year during follow-up, Dr. Aksamit reported.
The European bronchiectasis registry was partially funded by Bayer. Dr. Chalmers has been a consultant to Bayer and to AstraZeneca, Basilea, Grifols, Napp, and Raptor and has received research funding from Aradigm, AstraZeneca, Bayer, GlaxoSmithKline, and Pfizer. Dr. Aksamit had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT ATS 2017
Key clinical point:
Major finding: Patients with frequent exacerbations had twice the mortality rate, compared with bronchiectasis patients with no recent exacerbations.
Data source: A registry of 2,596 bronchiectasis patients from 10 centers in Europe and Israel.
Disclosures: The European bronchiectasis registry was partially funded by Bayer. Dr. Chalmers has been a consultant to Bayer and to AstraZeneca, Basilea, Grifols, Napp, and Raptor and has received research funding from Aradigm, AstraZeneca, Bayer, GlaxoSmithKline, and Pfizer. Dr. Aksamit had no disclosures.