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MOMENTUM 3 HeartMate 3 LVAD ‘practice changing’
ORLANDO – of follow-up in patients with advanced heart failure in the large multicenter MOMENTUM 3 trial, Mandeep R. Mehra, MD, reported at the annual meeting of the American College of Cardiology.
HeartMate 3 recipients had a 90% lower risk of undergoing reoperation to replace or remove their device because of malfunction, and a stroke rate half that in the HeartMate II group.
“This was the lowest rate of stroke ever seen in any LVAD trial,” according to Dr. Mehra, medical director of the Brigham and Women’s Hospital Heart and Vascular Center, Boston, and professor of medicine at Harvard Medical School.
“We believe this is a practice-changing result in the field, and that the real implication of our findings is to reassure those who refer or treat patients with advanced heart failure that it is perhaps going to be ignorant not to refer patients for consideration for destination therapy,” he said at a press conference highlighting the MOMENTUM 3 results, also presented in a late-breaking clinical trials session.
The HeartMate 3 is a miniaturized centrifugal-flow device that fits entirely within the chest, whereas the HeartMate II requires creation of a pocket in the abdomen. The HeartMate 3 was designed to prevent pump thrombosis – a common limiting problem with the HeartMate II and other LVADs – by employing three innovations: use of wide blood-flow passages to reduce shear stress and minimize disruption of red blood cells as they pass through the pump; reliance on magnetic levitation technology to create a frictionless pump with no mechanical bearings, which are subject to wear and tear; and incorporation of an artificial fixed pulse that speeds up and slows every 2 seconds in order to minimize blood stasis, which promotes thrombosis, the cardiologist explained in a video interview.
MOMENTUM 3 is the largest-ever randomized trial of LVAD therapy, involving 1,028 advanced heart failure patients at 69 U.S. centers. The study population is a mix of bridge-to-transplant patients and others who weren’t eligible for heart transplantation and are using their device as lifelong destination therapy. In an earlier report on the first 294 patients to reach 6 months of follow-up post implantation, Dr. Mehra and his coinvestigators showed that the HeartMate 3 group had a significantly lower incidence of the composite endpoint of disabling stroke or reoperation to replace or remove the device (N Engl J Med. 2017 Feb 2;376[5]:440-50).
At ACC 2018, he presented the prespecified 2-year analysis of results in the first 366 patients to reach that benchmark. The rate of survival free of disabling stroke or reoperation for device malfunction was 79.5% in the HeartMate 3 group and 60.2% with the HeartMate II, for a highly significant 54% reduction in the risk of bad outcome. Reoperation for device malfunction occurred in 1.6% of HeartMate 3 patients versus 17% of those with a HeartMate II, for a 92% reduction in risk. Two-year survival was 82.8% in the HeartMate 3 group and 76.2% in HeartMate II recipients.
The overall stroke rate was 10% with the HeartMate 3, compared with 19% with the older, axial-flow LVAD. The incidence of disabling stroke was 3% in the HeartMate 3 group and similar at 2% with the HeartMate II; however, nondisabling stroke occurred in only 3% of HeartMate 3 recipients, compared with 14% of patients with the HeartMate II.
“There has always been this notion that, ‘There are so many complications with this device, so let’s suffer with the disease rather than suffer with the pump.’ Now we’re showing that you don’t suffer with the pump as with the earlier-generation devices. I think this is going to open the gates for more referrals and more opportunities for destination therapy in patients who are deemed ineligible for transplant,” Dr. Mehra predicted.
Discussant James L. Janzuzzi Jr., called the MOMENTUM 3 results “a very-much-needed step forward.”
“Perhaps the most dramatic observation in this study is the dramatic reduction in thrombosis events requiring reoperation. In essence, this problem was entirely prevented by the use of this magnetically levitated centrifugal-flow device. Reoperation for thrombosis accounted for two-thirds of the reoperations in the HeartMate II group and the rate was zero in the HeartMate 3 population. Essentially, with this technology we’ve addressed a very important unmet need by reducing the onset of pump thrombosis, which is the precursor to either pump dysfunction or embolic stroke,” commented Dr. Januzzi, professor of medicine at Harvard Medical School, Boston.
Given the 83% survival rate at 2 years in the HeartMate 3 group in the MOMENTUM 3 trial, the on-average 50% survival at 10 years for heart transplant recipients, and the perpetual enormous shortage of donor organs, it’s time to consider a randomized trial of an advanced LVAD such as the HeartMate 3 versus heart transplantation, with quality-of-life outcomes front and center, he asserted.
Dr. Mehra was all for the idea. He noted that within the community of physicians and surgeons who provide care for advanced heart failure patients there is a growing move to replace problematic axial-flow LVADs requiring reoperation with a HeartMate 3 upgrade.
The MOMENTUM 3 trial is funded by Abbott. Dr. Mehra reported receiving research funds from and serving as a consultant to the company.
Simultaneous with his presentation at ACC 2018, the 2-year results of MOMENTUM 3 were published online at NEJM.org (doi: 10.1056/NEJMoa1800866).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SOURCE: Mehra M et al. ACC 18.
ORLANDO – of follow-up in patients with advanced heart failure in the large multicenter MOMENTUM 3 trial, Mandeep R. Mehra, MD, reported at the annual meeting of the American College of Cardiology.
HeartMate 3 recipients had a 90% lower risk of undergoing reoperation to replace or remove their device because of malfunction, and a stroke rate half that in the HeartMate II group.
“This was the lowest rate of stroke ever seen in any LVAD trial,” according to Dr. Mehra, medical director of the Brigham and Women’s Hospital Heart and Vascular Center, Boston, and professor of medicine at Harvard Medical School.
“We believe this is a practice-changing result in the field, and that the real implication of our findings is to reassure those who refer or treat patients with advanced heart failure that it is perhaps going to be ignorant not to refer patients for consideration for destination therapy,” he said at a press conference highlighting the MOMENTUM 3 results, also presented in a late-breaking clinical trials session.
The HeartMate 3 is a miniaturized centrifugal-flow device that fits entirely within the chest, whereas the HeartMate II requires creation of a pocket in the abdomen. The HeartMate 3 was designed to prevent pump thrombosis – a common limiting problem with the HeartMate II and other LVADs – by employing three innovations: use of wide blood-flow passages to reduce shear stress and minimize disruption of red blood cells as they pass through the pump; reliance on magnetic levitation technology to create a frictionless pump with no mechanical bearings, which are subject to wear and tear; and incorporation of an artificial fixed pulse that speeds up and slows every 2 seconds in order to minimize blood stasis, which promotes thrombosis, the cardiologist explained in a video interview.
MOMENTUM 3 is the largest-ever randomized trial of LVAD therapy, involving 1,028 advanced heart failure patients at 69 U.S. centers. The study population is a mix of bridge-to-transplant patients and others who weren’t eligible for heart transplantation and are using their device as lifelong destination therapy. In an earlier report on the first 294 patients to reach 6 months of follow-up post implantation, Dr. Mehra and his coinvestigators showed that the HeartMate 3 group had a significantly lower incidence of the composite endpoint of disabling stroke or reoperation to replace or remove the device (N Engl J Med. 2017 Feb 2;376[5]:440-50).
At ACC 2018, he presented the prespecified 2-year analysis of results in the first 366 patients to reach that benchmark. The rate of survival free of disabling stroke or reoperation for device malfunction was 79.5% in the HeartMate 3 group and 60.2% with the HeartMate II, for a highly significant 54% reduction in the risk of bad outcome. Reoperation for device malfunction occurred in 1.6% of HeartMate 3 patients versus 17% of those with a HeartMate II, for a 92% reduction in risk. Two-year survival was 82.8% in the HeartMate 3 group and 76.2% in HeartMate II recipients.
The overall stroke rate was 10% with the HeartMate 3, compared with 19% with the older, axial-flow LVAD. The incidence of disabling stroke was 3% in the HeartMate 3 group and similar at 2% with the HeartMate II; however, nondisabling stroke occurred in only 3% of HeartMate 3 recipients, compared with 14% of patients with the HeartMate II.
“There has always been this notion that, ‘There are so many complications with this device, so let’s suffer with the disease rather than suffer with the pump.’ Now we’re showing that you don’t suffer with the pump as with the earlier-generation devices. I think this is going to open the gates for more referrals and more opportunities for destination therapy in patients who are deemed ineligible for transplant,” Dr. Mehra predicted.
Discussant James L. Janzuzzi Jr., called the MOMENTUM 3 results “a very-much-needed step forward.”
“Perhaps the most dramatic observation in this study is the dramatic reduction in thrombosis events requiring reoperation. In essence, this problem was entirely prevented by the use of this magnetically levitated centrifugal-flow device. Reoperation for thrombosis accounted for two-thirds of the reoperations in the HeartMate II group and the rate was zero in the HeartMate 3 population. Essentially, with this technology we’ve addressed a very important unmet need by reducing the onset of pump thrombosis, which is the precursor to either pump dysfunction or embolic stroke,” commented Dr. Januzzi, professor of medicine at Harvard Medical School, Boston.
Given the 83% survival rate at 2 years in the HeartMate 3 group in the MOMENTUM 3 trial, the on-average 50% survival at 10 years for heart transplant recipients, and the perpetual enormous shortage of donor organs, it’s time to consider a randomized trial of an advanced LVAD such as the HeartMate 3 versus heart transplantation, with quality-of-life outcomes front and center, he asserted.
Dr. Mehra was all for the idea. He noted that within the community of physicians and surgeons who provide care for advanced heart failure patients there is a growing move to replace problematic axial-flow LVADs requiring reoperation with a HeartMate 3 upgrade.
The MOMENTUM 3 trial is funded by Abbott. Dr. Mehra reported receiving research funds from and serving as a consultant to the company.
Simultaneous with his presentation at ACC 2018, the 2-year results of MOMENTUM 3 were published online at NEJM.org (doi: 10.1056/NEJMoa1800866).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SOURCE: Mehra M et al. ACC 18.
ORLANDO – of follow-up in patients with advanced heart failure in the large multicenter MOMENTUM 3 trial, Mandeep R. Mehra, MD, reported at the annual meeting of the American College of Cardiology.
HeartMate 3 recipients had a 90% lower risk of undergoing reoperation to replace or remove their device because of malfunction, and a stroke rate half that in the HeartMate II group.
“This was the lowest rate of stroke ever seen in any LVAD trial,” according to Dr. Mehra, medical director of the Brigham and Women’s Hospital Heart and Vascular Center, Boston, and professor of medicine at Harvard Medical School.
“We believe this is a practice-changing result in the field, and that the real implication of our findings is to reassure those who refer or treat patients with advanced heart failure that it is perhaps going to be ignorant not to refer patients for consideration for destination therapy,” he said at a press conference highlighting the MOMENTUM 3 results, also presented in a late-breaking clinical trials session.
The HeartMate 3 is a miniaturized centrifugal-flow device that fits entirely within the chest, whereas the HeartMate II requires creation of a pocket in the abdomen. The HeartMate 3 was designed to prevent pump thrombosis – a common limiting problem with the HeartMate II and other LVADs – by employing three innovations: use of wide blood-flow passages to reduce shear stress and minimize disruption of red blood cells as they pass through the pump; reliance on magnetic levitation technology to create a frictionless pump with no mechanical bearings, which are subject to wear and tear; and incorporation of an artificial fixed pulse that speeds up and slows every 2 seconds in order to minimize blood stasis, which promotes thrombosis, the cardiologist explained in a video interview.
MOMENTUM 3 is the largest-ever randomized trial of LVAD therapy, involving 1,028 advanced heart failure patients at 69 U.S. centers. The study population is a mix of bridge-to-transplant patients and others who weren’t eligible for heart transplantation and are using their device as lifelong destination therapy. In an earlier report on the first 294 patients to reach 6 months of follow-up post implantation, Dr. Mehra and his coinvestigators showed that the HeartMate 3 group had a significantly lower incidence of the composite endpoint of disabling stroke or reoperation to replace or remove the device (N Engl J Med. 2017 Feb 2;376[5]:440-50).
At ACC 2018, he presented the prespecified 2-year analysis of results in the first 366 patients to reach that benchmark. The rate of survival free of disabling stroke or reoperation for device malfunction was 79.5% in the HeartMate 3 group and 60.2% with the HeartMate II, for a highly significant 54% reduction in the risk of bad outcome. Reoperation for device malfunction occurred in 1.6% of HeartMate 3 patients versus 17% of those with a HeartMate II, for a 92% reduction in risk. Two-year survival was 82.8% in the HeartMate 3 group and 76.2% in HeartMate II recipients.
The overall stroke rate was 10% with the HeartMate 3, compared with 19% with the older, axial-flow LVAD. The incidence of disabling stroke was 3% in the HeartMate 3 group and similar at 2% with the HeartMate II; however, nondisabling stroke occurred in only 3% of HeartMate 3 recipients, compared with 14% of patients with the HeartMate II.
“There has always been this notion that, ‘There are so many complications with this device, so let’s suffer with the disease rather than suffer with the pump.’ Now we’re showing that you don’t suffer with the pump as with the earlier-generation devices. I think this is going to open the gates for more referrals and more opportunities for destination therapy in patients who are deemed ineligible for transplant,” Dr. Mehra predicted.
Discussant James L. Janzuzzi Jr., called the MOMENTUM 3 results “a very-much-needed step forward.”
“Perhaps the most dramatic observation in this study is the dramatic reduction in thrombosis events requiring reoperation. In essence, this problem was entirely prevented by the use of this magnetically levitated centrifugal-flow device. Reoperation for thrombosis accounted for two-thirds of the reoperations in the HeartMate II group and the rate was zero in the HeartMate 3 population. Essentially, with this technology we’ve addressed a very important unmet need by reducing the onset of pump thrombosis, which is the precursor to either pump dysfunction or embolic stroke,” commented Dr. Januzzi, professor of medicine at Harvard Medical School, Boston.
Given the 83% survival rate at 2 years in the HeartMate 3 group in the MOMENTUM 3 trial, the on-average 50% survival at 10 years for heart transplant recipients, and the perpetual enormous shortage of donor organs, it’s time to consider a randomized trial of an advanced LVAD such as the HeartMate 3 versus heart transplantation, with quality-of-life outcomes front and center, he asserted.
Dr. Mehra was all for the idea. He noted that within the community of physicians and surgeons who provide care for advanced heart failure patients there is a growing move to replace problematic axial-flow LVADs requiring reoperation with a HeartMate 3 upgrade.
The MOMENTUM 3 trial is funded by Abbott. Dr. Mehra reported receiving research funds from and serving as a consultant to the company.
Simultaneous with his presentation at ACC 2018, the 2-year results of MOMENTUM 3 were published online at NEJM.org (doi: 10.1056/NEJMoa1800866).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SOURCE: Mehra M et al. ACC 18.
REPORTING FROM ACC 18
Key clinical point: Landmark trial paves way to much wider use of LVADs as destination therapy.
Major finding: The 2-year rate of survival free of disabling stroke or reoperation to replace or remove a malfunctioning LVAD was 79.5% with the novel HeartMate 3 LVAD, compared with 60.2% with the commonly used HeartMate II axial-flow device.
Study details: This was a randomized, unblinded, multicenter study of more than 1,000 patients with advanced heart failure.
Disclosures: The MOMENTUM 3 trial was funded by Abbott. The presenter reported receiving research grants from and serving as a consultant to the company.
Source: Mehra MR et al. ACC 18.
ODYSSEY Outcomes trial redefines secondary cardiovascular prevention
ORLANDO – In what was hailed as a major advance in preventive cardiology, the ODYSSEY Outcomes trial has shown that adding the PCSK9 inhibitor alirocumab on top of intensive statin therapy reduced major adverse cardiovascular events and all-cause mortality significantly more than placebo plus intensive statin therapy in patients with a recent acute coronary syndrome and an elevated on-statin LDL cholesterol level.
ODYSSEY Outcomes was a double-blind trial in which 18,924 patients at 1,315 sites in 57 countries were randomized to alirocumab (Praluent) or placebo plus background high-intensity statin therapy starting a median of 2.5 months after an acute coronary syndrome. All participants had to have a baseline LDL cholesterol level of 70 mg/dL or higher despite intensive statin therapy. Alirocumab was titrated to maintain a target LDL of 25-50 mg/dL. An LDL of 15-25 mg/dL was deemed acceptable, but if the level dropped below 15 mg/dL on two consecutive measurements the patient was blindly switched to placebo, as occurred in 7.7% of the alirocumab group.
The primary study endpoint was a composite outcome comprised of CHD (coronary heart disease) death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. During a median 2.8 years of follow-up, this outcome occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for a statistically significant and clinically meaningful 15% reduction in relative risk. The CHD death rates in the two study arms were similar; however, the other three components of the primary endpoint occurred significantly less often in the alirocumab group: The risk of nonfatal MI was 14% less (6.6% vs. 7.6%), ischemic stroke was 27% less (1.2 vs. 1.6%), and unstable angina was 39% less (0.4% vs. 0.6%).
All-cause mortality occurred in 3.5% of patients receiving alirocumab and 4.1% on placebo, once again for a statistically significant 15% reduction in risk. This was a major achievement, since even statins haven’t shown a mortality benefit in the post-ACS setting, observed Dr. Steg, cochair of the study.
The greatest benefits were seen in the 5,629 participants with a baseline LDL of 100 mg/dL or more on high-intensity statin therapy. In this large subgroup at highest baseline risk, alirocumab resulted in an absolute 3.4% risk reduction and a 24% reduction in relative risk of MACE. All-cause mortality decreased by an absolute 1.7%, translating to a 29% relative risk reduction. The number-needed-to-treat (NNT) for the duration of the study in order to prevent one additional MACE event in this group was 29, with an NNT to prevent one additional death of 60, added Dr. Steg, professor of cardiology at the University of Paris and chief of cardiology at Bichat Hospital.
“The risk/benefit for alirocumab is extraordinarily favorable. There was almost no risk over the course of the trial. There was no increase in neurocognitive disorders, new-onset or worsening diabetes, cataracts, or hemorrhagic stroke,” the cardiologist said.
Indeed, the sole adverse event that occurred more frequently in the alirocumab group was mild local injection site reactions, which occurred in 3.8% of the alirocumab group and 2.1% of controls.
There was a tendency for LDL to creep upward in both the alirocumab and placebo arms over the course of follow-up. Dr. Steg attributed this to down-titration or cessation of alirocumab as per protocol along with the inability of a substantial proportion of patients to tolerate intensive statin therapy. Most study participants had never been on a statin until their ACS.
A year ago at ACC 2017, other investigators presented the results of FOURIER, a large clinical outcomes trial of evolocumab (Repatha), another PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. FOURIER also showed a 15% relative risk reduction in major adverse cardiovascular events, but unlike in ODYSSEY Outcomes, there was no significant impact upon mortality. Dr. Steg attributed this to several key differences between the two trials.
The post-ACS population of ODYSSEY Outcomes was on average higher-risk than FOURIER participants, who had stable atherosclerotic cardiovascular disease. The background statin therapy was more intensive in ODYSSEY, and the average follow-up was close to 8 months longer, too.
The study population is representative of an enormous number of patients seen in clinical practice, added Dr. Fuster, professor of medicine and physician-in-chief at Mount Sinai Hospital in New York. He estimated that one-third of patients who experience ACS can’t subsequently get their LDL down to the 70 mg/dL range on statin therapy, generally because of drug intolerance.
He voiced a concern: “Up until now, the feasibility and affordability of using this type of drug has been extremely difficult. I hope this particular study is a trigger – a catalyzer – for making this drug much more available to people who need it.”
The study met with an enthusiastic audience reception. Prior to presentation of the results at the meeting’s opening session, 79% of the audience of more than 4,000 in the main arena indicated they either don’t prescribe PCSK9 inhibitors or do so only a handful of times per year.
Immediately after seeing the data, 62% of the audience said their practice will change as a result of the study findings.
ODYSSEY Outcomes was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Steg reported serving as a consultant to and receiving research grants from those pharmaceutical companies and numerous others.
bjancin@frontlinemedcom.com
SOURCE: Steg GP.
ORLANDO – In what was hailed as a major advance in preventive cardiology, the ODYSSEY Outcomes trial has shown that adding the PCSK9 inhibitor alirocumab on top of intensive statin therapy reduced major adverse cardiovascular events and all-cause mortality significantly more than placebo plus intensive statin therapy in patients with a recent acute coronary syndrome and an elevated on-statin LDL cholesterol level.
ODYSSEY Outcomes was a double-blind trial in which 18,924 patients at 1,315 sites in 57 countries were randomized to alirocumab (Praluent) or placebo plus background high-intensity statin therapy starting a median of 2.5 months after an acute coronary syndrome. All participants had to have a baseline LDL cholesterol level of 70 mg/dL or higher despite intensive statin therapy. Alirocumab was titrated to maintain a target LDL of 25-50 mg/dL. An LDL of 15-25 mg/dL was deemed acceptable, but if the level dropped below 15 mg/dL on two consecutive measurements the patient was blindly switched to placebo, as occurred in 7.7% of the alirocumab group.
The primary study endpoint was a composite outcome comprised of CHD (coronary heart disease) death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. During a median 2.8 years of follow-up, this outcome occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for a statistically significant and clinically meaningful 15% reduction in relative risk. The CHD death rates in the two study arms were similar; however, the other three components of the primary endpoint occurred significantly less often in the alirocumab group: The risk of nonfatal MI was 14% less (6.6% vs. 7.6%), ischemic stroke was 27% less (1.2 vs. 1.6%), and unstable angina was 39% less (0.4% vs. 0.6%).
All-cause mortality occurred in 3.5% of patients receiving alirocumab and 4.1% on placebo, once again for a statistically significant 15% reduction in risk. This was a major achievement, since even statins haven’t shown a mortality benefit in the post-ACS setting, observed Dr. Steg, cochair of the study.
The greatest benefits were seen in the 5,629 participants with a baseline LDL of 100 mg/dL or more on high-intensity statin therapy. In this large subgroup at highest baseline risk, alirocumab resulted in an absolute 3.4% risk reduction and a 24% reduction in relative risk of MACE. All-cause mortality decreased by an absolute 1.7%, translating to a 29% relative risk reduction. The number-needed-to-treat (NNT) for the duration of the study in order to prevent one additional MACE event in this group was 29, with an NNT to prevent one additional death of 60, added Dr. Steg, professor of cardiology at the University of Paris and chief of cardiology at Bichat Hospital.
“The risk/benefit for alirocumab is extraordinarily favorable. There was almost no risk over the course of the trial. There was no increase in neurocognitive disorders, new-onset or worsening diabetes, cataracts, or hemorrhagic stroke,” the cardiologist said.
Indeed, the sole adverse event that occurred more frequently in the alirocumab group was mild local injection site reactions, which occurred in 3.8% of the alirocumab group and 2.1% of controls.
There was a tendency for LDL to creep upward in both the alirocumab and placebo arms over the course of follow-up. Dr. Steg attributed this to down-titration or cessation of alirocumab as per protocol along with the inability of a substantial proportion of patients to tolerate intensive statin therapy. Most study participants had never been on a statin until their ACS.
A year ago at ACC 2017, other investigators presented the results of FOURIER, a large clinical outcomes trial of evolocumab (Repatha), another PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. FOURIER also showed a 15% relative risk reduction in major adverse cardiovascular events, but unlike in ODYSSEY Outcomes, there was no significant impact upon mortality. Dr. Steg attributed this to several key differences between the two trials.
The post-ACS population of ODYSSEY Outcomes was on average higher-risk than FOURIER participants, who had stable atherosclerotic cardiovascular disease. The background statin therapy was more intensive in ODYSSEY, and the average follow-up was close to 8 months longer, too.
The study population is representative of an enormous number of patients seen in clinical practice, added Dr. Fuster, professor of medicine and physician-in-chief at Mount Sinai Hospital in New York. He estimated that one-third of patients who experience ACS can’t subsequently get their LDL down to the 70 mg/dL range on statin therapy, generally because of drug intolerance.
He voiced a concern: “Up until now, the feasibility and affordability of using this type of drug has been extremely difficult. I hope this particular study is a trigger – a catalyzer – for making this drug much more available to people who need it.”
The study met with an enthusiastic audience reception. Prior to presentation of the results at the meeting’s opening session, 79% of the audience of more than 4,000 in the main arena indicated they either don’t prescribe PCSK9 inhibitors or do so only a handful of times per year.
Immediately after seeing the data, 62% of the audience said their practice will change as a result of the study findings.
ODYSSEY Outcomes was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Steg reported serving as a consultant to and receiving research grants from those pharmaceutical companies and numerous others.
bjancin@frontlinemedcom.com
SOURCE: Steg GP.
ORLANDO – In what was hailed as a major advance in preventive cardiology, the ODYSSEY Outcomes trial has shown that adding the PCSK9 inhibitor alirocumab on top of intensive statin therapy reduced major adverse cardiovascular events and all-cause mortality significantly more than placebo plus intensive statin therapy in patients with a recent acute coronary syndrome and an elevated on-statin LDL cholesterol level.
ODYSSEY Outcomes was a double-blind trial in which 18,924 patients at 1,315 sites in 57 countries were randomized to alirocumab (Praluent) or placebo plus background high-intensity statin therapy starting a median of 2.5 months after an acute coronary syndrome. All participants had to have a baseline LDL cholesterol level of 70 mg/dL or higher despite intensive statin therapy. Alirocumab was titrated to maintain a target LDL of 25-50 mg/dL. An LDL of 15-25 mg/dL was deemed acceptable, but if the level dropped below 15 mg/dL on two consecutive measurements the patient was blindly switched to placebo, as occurred in 7.7% of the alirocumab group.
The primary study endpoint was a composite outcome comprised of CHD (coronary heart disease) death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. During a median 2.8 years of follow-up, this outcome occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for a statistically significant and clinically meaningful 15% reduction in relative risk. The CHD death rates in the two study arms were similar; however, the other three components of the primary endpoint occurred significantly less often in the alirocumab group: The risk of nonfatal MI was 14% less (6.6% vs. 7.6%), ischemic stroke was 27% less (1.2 vs. 1.6%), and unstable angina was 39% less (0.4% vs. 0.6%).
All-cause mortality occurred in 3.5% of patients receiving alirocumab and 4.1% on placebo, once again for a statistically significant 15% reduction in risk. This was a major achievement, since even statins haven’t shown a mortality benefit in the post-ACS setting, observed Dr. Steg, cochair of the study.
The greatest benefits were seen in the 5,629 participants with a baseline LDL of 100 mg/dL or more on high-intensity statin therapy. In this large subgroup at highest baseline risk, alirocumab resulted in an absolute 3.4% risk reduction and a 24% reduction in relative risk of MACE. All-cause mortality decreased by an absolute 1.7%, translating to a 29% relative risk reduction. The number-needed-to-treat (NNT) for the duration of the study in order to prevent one additional MACE event in this group was 29, with an NNT to prevent one additional death of 60, added Dr. Steg, professor of cardiology at the University of Paris and chief of cardiology at Bichat Hospital.
“The risk/benefit for alirocumab is extraordinarily favorable. There was almost no risk over the course of the trial. There was no increase in neurocognitive disorders, new-onset or worsening diabetes, cataracts, or hemorrhagic stroke,” the cardiologist said.
Indeed, the sole adverse event that occurred more frequently in the alirocumab group was mild local injection site reactions, which occurred in 3.8% of the alirocumab group and 2.1% of controls.
There was a tendency for LDL to creep upward in both the alirocumab and placebo arms over the course of follow-up. Dr. Steg attributed this to down-titration or cessation of alirocumab as per protocol along with the inability of a substantial proportion of patients to tolerate intensive statin therapy. Most study participants had never been on a statin until their ACS.
A year ago at ACC 2017, other investigators presented the results of FOURIER, a large clinical outcomes trial of evolocumab (Repatha), another PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. FOURIER also showed a 15% relative risk reduction in major adverse cardiovascular events, but unlike in ODYSSEY Outcomes, there was no significant impact upon mortality. Dr. Steg attributed this to several key differences between the two trials.
The post-ACS population of ODYSSEY Outcomes was on average higher-risk than FOURIER participants, who had stable atherosclerotic cardiovascular disease. The background statin therapy was more intensive in ODYSSEY, and the average follow-up was close to 8 months longer, too.
The study population is representative of an enormous number of patients seen in clinical practice, added Dr. Fuster, professor of medicine and physician-in-chief at Mount Sinai Hospital in New York. He estimated that one-third of patients who experience ACS can’t subsequently get their LDL down to the 70 mg/dL range on statin therapy, generally because of drug intolerance.
He voiced a concern: “Up until now, the feasibility and affordability of using this type of drug has been extremely difficult. I hope this particular study is a trigger – a catalyzer – for making this drug much more available to people who need it.”
The study met with an enthusiastic audience reception. Prior to presentation of the results at the meeting’s opening session, 79% of the audience of more than 4,000 in the main arena indicated they either don’t prescribe PCSK9 inhibitors or do so only a handful of times per year.
Immediately after seeing the data, 62% of the audience said their practice will change as a result of the study findings.
ODYSSEY Outcomes was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Steg reported serving as a consultant to and receiving research grants from those pharmaceutical companies and numerous others.
bjancin@frontlinemedcom.com
SOURCE: Steg GP.
REPORTING FROM ACC 2018
Key clinical point: Alirocumab reduced both all-cause mortality and major adverse cardiovascular events in high-risk patients with a recent acute coronary syndrome.
Major finding: Alirocumab reduced MACE by 15% and all-cause mortality by an equal margin compared with placebo in patients with a recent acute coronary syndrome and elevated LDL cholesterol despite intensive statin therapy alone.
Study details: The ODYSSEY Outcomes trial was a double-blind, randomized trial of nearly 19,000 patients with a recent acute coronary syndrome and an LDL cholesterol of 70 mg/dL or more despite intensive statin therapy.
Disclosures: ODYSSEY Outcomes was funded by Sanofi and Regeneron Pharmaceuticals. The presenter reported serving as a consultant to and receiving research grants from those pharmaceutical companies and numerous others.
Source: Steig, GP.
2017 was a big year for psoriatic arthritis
MAUI, HAWAII – 2017 was a banner year in the field of psoriatic arthritis, marked by a huge bump in the number of publications on the topic along with the approval of three additional drugs, Arthur Kavanaugh, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“There is a tremendous amount of excitement now in the field of psoriatic arthritis,” observed Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego.
Together with his colleague Eric M. Ruderman, MD, Dr. Kavanaugh highlighted the three new drug approvals for psoriatic arthritis in 2017 – abatacept(Orencia), tofacitinib(Xeljanz), and ixekizumab(Taltz) – and also discussed important recent studies of several drugs already available.
Abatacept
In the pivotal double-blind, phase 3 trial involving 424 psoriatic arthritis patients, roughly 60% with prior exposure to a tumor necrosis factor inhibitor and 60% on concomitant methotrexate, the proportion of patients with at least 20% improvement in the American College of Rheumatology criteria (ACR20) was 39.4% in patients on the selective T-cell costimulation modulator, compared with 22.3% among placebo-treated controls. The benefit on psoriasis lesions was modest, and there was no significant difference between the two study arms in terms of Health Assessment Questionnaire-Disability Index response rates (Ann Rheum Dis. 2017 Sep;76[9]:1550-8).
“I think we could say the effect is modest,” Dr. Kavanaugh said. “The challenge to us still is to identify patients who are going to have a good response, likely the patients with more joint than skin symptoms.”
An attractive feature of the drug is that its safety profile is well known as a result of its extensive track record in treating RA, he added.
Tofacitinib
On the basis of the phase 3 OPAL Beyond (N Engl J Med. 2017 Oct 19;377[16]:1525-36) and OPAL Broaden (N Engl J Med. 2017 Oct 19;377[16]:1537-50) clinical trials, the dose approved by the Food and Drug Administration for psoriatic arthritis was 5 mg b.i.d.. There was a higher ACR20 response rate with 10 mg than 5 mg b.i.d. in OPAL Broaden, but not in OPAL Beyond. And since there was a suggestion of a higher adverse event rate with the 10-mg b.i.d. dosing without unequivocal evidence of superior efficacy, the Food and Drug Administration – which always puts safety first – went with 5 mg b.i.d., Dr. Ruderman explained.
Ixekizumab
In the phase 3, double-blind SPIRIT-P1 trial, featuring 417 biologic-naive psoriatic arthritis patients, the ACR20 response rate at week 24 was 62.1% with the interleukin-17A antagonist at 80 mg given subcutaneously every 2 weeks and 57.9% when dosed every 4 weeks, compared with 57.4% with adalimumab(Humira) at 40 mg every 2 weeks and 30.2% with placebo (Ann Rheum Dis. 2017 Jan;76[1]:79-87). The FDA-approved regimen was a 160-mg loading dose of ixekizumab, followed by 80 mg every 4 weeks.
Dr. Kavanaugh noted that an international team of investigators has identified beta-defensin 2 as an easily measurable biomarker of interleukin-17A–driven skin pathology after evaluating 170 proteins expressed in blood, psoriasis lesions, and nonlesional skin. It was a small study, with eight psoriasis patients and eight healthy controls studied before and after receiving secukinumab(Cosentyx), a monoclonal antibody directed against interleukin-17A (J Allergy Clin Immunol. 2017 Mar;139[3]:923-932.e8). But it’s a study with big potential implications.
“This natural antibiotic compound we make that’s in the skin might be a marker of responsiveness to anti–interleukin-17 therapy. It could help in deciding which patients get which drugs. This needs further study, especially now that we’re using anti–interleukin-17 drugs more now,” the rheumatologist said.
The year 2017 also brought important new studies of several drugs already available for psoriatic arthritis.
Intravenous golimumab (Simponi Aria)
Dr. Kavanaugh was first author of the GO-VIBRANT study, a phase 3, double-blind clinical trial in which 480 biologic-naive psoriatic arthritis patients were randomized to a 30-minute infusion of IV golimumab at 2 mg/kg or placebo at weeks 0, 4, 12, and 20.
The primary endpoint, an ACR20 response at week 14, was achieved in 75.1% of patients on the tumor necrosis factor inhibitor versus 21.8% on placebo. An ACR50 response occurred in 43.6% of patients on IV golimumab, compared with 6.3% on placebo, and a Psoriasis and Area Severity Index 75 skin response was achieved in 59.2% on IV golimumab and 13.6% of controls. At week 24, the IV golimumab group demonstrated significantly less radiographic progression as measured by the total modified Sharp/van der Heijde score. The drug was well tolerated, with no opportunistic infections or tuberculosis, and the infusion reaction rate was below 2% (Arthritis Rheumatol. 2017 Nov;69[11]:2151-61).
Secukinumab
In a recent update of the 606-patient FUTURE 1 trial, secukinumab resulted in clinically meaningful improvement in key patient-reported outcomes at week 24, including global assessment of disease activity, which decreased by a mean of 20.6 and 20 points in patients on 150 and 75 mg, respectively, every 4 weeks, compared with a 7.4-point drop in placebo-treated controls.
Psoriatic arthritis quality of life scores improved by 3.5 and 3.2 points in the two secukinumab arms, compared with 0.4 points in controls. Dermatology Life Quality Index scores improved by 8.8 and 7.9 points, versus 0.7 in controls. Patients on the interleukin-17A inhibitor also showed significantly greater improvement in self-assessments measuring pain and fatigue (Ann Rheum Dis. 2017 Jan;76[1]:203-7).
Apremilast (Otezla)
At the 2018 meeting of the American Academy of Dermatology, Dr. Kavanaugh presented 5-year outcomes of the open-label extension of the 504-patient, phase 3 PALACE-1 trial. In an as-observed analysis, patients on apremilast 30 mg b.i.d. up to week 260 had a 71.7% ACR20 response rate, a 48.6% ACR50 response rate, and a 28.4% ACR70 response. Eighty percent of patients on the oral phosphodiesterase-4 (PDE-4) inhibitor had a dactylitis count of 0, and 54.5% had a Maastricht Ankylosing Spondylitis Enthesitis Score of 0.
In a report from the 219-patient, phase 3B ACTIVE trial, investigators showed that biologic-naive patients randomized to apremilast at 30 mg b.i.d. had a significantly greater ACR20 response as early as week 2, which was the first assessment. At that point, the ACR20 rate was 16.4% with apremilast, compared with 6.4% in placebo-treated controls. The apremilast group also demonstrated significant early improvements in patient-reported outcomes, including the Health Assessment Questionnaire-Disability Index, morning stiffness, and enthesitis severity.
The primary outcome, the ACR20 rate at week 16, was 38.2% with active treatment versus 20.2% in controls (Ann Rheum Dis. 2018 Jan 17. doi: 10.1136/annrheumdis-2017-211568).
“The main advantage of apremilast is safety – and that’s a big advantage,” Dr. Kavanaugh commented.
Military physicians tell him they are prescribing a lot of apremilast for armed forces deploying overseas because it’s not immunosuppressive and doesn’t entail laboratory testing.
The research agenda for PDE-4 inhibition in psoriatic disease is extensive, he noted. There is a need for formal studies of PDE-4 inhibition in combination with conventional disease-modifying antirheumatic drugs or biologics. Topical formulations, once-daily dosing, and the possibility that PDE-4 inhibition might be the preferred therapy in patients with certain comorbid conditions, such as chronic obstructive pulmonary disease or a history of recurrent infections, are all topics worthy of study. A biomarker to identify in advance which patients with psoriatic arthritis or psoriasis will attain maximum clinical benefit from apremilast, and in which domains, would be of enormous help to clinicians.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
MAUI, HAWAII – 2017 was a banner year in the field of psoriatic arthritis, marked by a huge bump in the number of publications on the topic along with the approval of three additional drugs, Arthur Kavanaugh, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“There is a tremendous amount of excitement now in the field of psoriatic arthritis,” observed Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego.
Together with his colleague Eric M. Ruderman, MD, Dr. Kavanaugh highlighted the three new drug approvals for psoriatic arthritis in 2017 – abatacept(Orencia), tofacitinib(Xeljanz), and ixekizumab(Taltz) – and also discussed important recent studies of several drugs already available.
Abatacept
In the pivotal double-blind, phase 3 trial involving 424 psoriatic arthritis patients, roughly 60% with prior exposure to a tumor necrosis factor inhibitor and 60% on concomitant methotrexate, the proportion of patients with at least 20% improvement in the American College of Rheumatology criteria (ACR20) was 39.4% in patients on the selective T-cell costimulation modulator, compared with 22.3% among placebo-treated controls. The benefit on psoriasis lesions was modest, and there was no significant difference between the two study arms in terms of Health Assessment Questionnaire-Disability Index response rates (Ann Rheum Dis. 2017 Sep;76[9]:1550-8).
“I think we could say the effect is modest,” Dr. Kavanaugh said. “The challenge to us still is to identify patients who are going to have a good response, likely the patients with more joint than skin symptoms.”
An attractive feature of the drug is that its safety profile is well known as a result of its extensive track record in treating RA, he added.
Tofacitinib
On the basis of the phase 3 OPAL Beyond (N Engl J Med. 2017 Oct 19;377[16]:1525-36) and OPAL Broaden (N Engl J Med. 2017 Oct 19;377[16]:1537-50) clinical trials, the dose approved by the Food and Drug Administration for psoriatic arthritis was 5 mg b.i.d.. There was a higher ACR20 response rate with 10 mg than 5 mg b.i.d. in OPAL Broaden, but not in OPAL Beyond. And since there was a suggestion of a higher adverse event rate with the 10-mg b.i.d. dosing without unequivocal evidence of superior efficacy, the Food and Drug Administration – which always puts safety first – went with 5 mg b.i.d., Dr. Ruderman explained.
Ixekizumab
In the phase 3, double-blind SPIRIT-P1 trial, featuring 417 biologic-naive psoriatic arthritis patients, the ACR20 response rate at week 24 was 62.1% with the interleukin-17A antagonist at 80 mg given subcutaneously every 2 weeks and 57.9% when dosed every 4 weeks, compared with 57.4% with adalimumab(Humira) at 40 mg every 2 weeks and 30.2% with placebo (Ann Rheum Dis. 2017 Jan;76[1]:79-87). The FDA-approved regimen was a 160-mg loading dose of ixekizumab, followed by 80 mg every 4 weeks.
Dr. Kavanaugh noted that an international team of investigators has identified beta-defensin 2 as an easily measurable biomarker of interleukin-17A–driven skin pathology after evaluating 170 proteins expressed in blood, psoriasis lesions, and nonlesional skin. It was a small study, with eight psoriasis patients and eight healthy controls studied before and after receiving secukinumab(Cosentyx), a monoclonal antibody directed against interleukin-17A (J Allergy Clin Immunol. 2017 Mar;139[3]:923-932.e8). But it’s a study with big potential implications.
“This natural antibiotic compound we make that’s in the skin might be a marker of responsiveness to anti–interleukin-17 therapy. It could help in deciding which patients get which drugs. This needs further study, especially now that we’re using anti–interleukin-17 drugs more now,” the rheumatologist said.
The year 2017 also brought important new studies of several drugs already available for psoriatic arthritis.
Intravenous golimumab (Simponi Aria)
Dr. Kavanaugh was first author of the GO-VIBRANT study, a phase 3, double-blind clinical trial in which 480 biologic-naive psoriatic arthritis patients were randomized to a 30-minute infusion of IV golimumab at 2 mg/kg or placebo at weeks 0, 4, 12, and 20.
The primary endpoint, an ACR20 response at week 14, was achieved in 75.1% of patients on the tumor necrosis factor inhibitor versus 21.8% on placebo. An ACR50 response occurred in 43.6% of patients on IV golimumab, compared with 6.3% on placebo, and a Psoriasis and Area Severity Index 75 skin response was achieved in 59.2% on IV golimumab and 13.6% of controls. At week 24, the IV golimumab group demonstrated significantly less radiographic progression as measured by the total modified Sharp/van der Heijde score. The drug was well tolerated, with no opportunistic infections or tuberculosis, and the infusion reaction rate was below 2% (Arthritis Rheumatol. 2017 Nov;69[11]:2151-61).
Secukinumab
In a recent update of the 606-patient FUTURE 1 trial, secukinumab resulted in clinically meaningful improvement in key patient-reported outcomes at week 24, including global assessment of disease activity, which decreased by a mean of 20.6 and 20 points in patients on 150 and 75 mg, respectively, every 4 weeks, compared with a 7.4-point drop in placebo-treated controls.
Psoriatic arthritis quality of life scores improved by 3.5 and 3.2 points in the two secukinumab arms, compared with 0.4 points in controls. Dermatology Life Quality Index scores improved by 8.8 and 7.9 points, versus 0.7 in controls. Patients on the interleukin-17A inhibitor also showed significantly greater improvement in self-assessments measuring pain and fatigue (Ann Rheum Dis. 2017 Jan;76[1]:203-7).
Apremilast (Otezla)
At the 2018 meeting of the American Academy of Dermatology, Dr. Kavanaugh presented 5-year outcomes of the open-label extension of the 504-patient, phase 3 PALACE-1 trial. In an as-observed analysis, patients on apremilast 30 mg b.i.d. up to week 260 had a 71.7% ACR20 response rate, a 48.6% ACR50 response rate, and a 28.4% ACR70 response. Eighty percent of patients on the oral phosphodiesterase-4 (PDE-4) inhibitor had a dactylitis count of 0, and 54.5% had a Maastricht Ankylosing Spondylitis Enthesitis Score of 0.
In a report from the 219-patient, phase 3B ACTIVE trial, investigators showed that biologic-naive patients randomized to apremilast at 30 mg b.i.d. had a significantly greater ACR20 response as early as week 2, which was the first assessment. At that point, the ACR20 rate was 16.4% with apremilast, compared with 6.4% in placebo-treated controls. The apremilast group also demonstrated significant early improvements in patient-reported outcomes, including the Health Assessment Questionnaire-Disability Index, morning stiffness, and enthesitis severity.
The primary outcome, the ACR20 rate at week 16, was 38.2% with active treatment versus 20.2% in controls (Ann Rheum Dis. 2018 Jan 17. doi: 10.1136/annrheumdis-2017-211568).
“The main advantage of apremilast is safety – and that’s a big advantage,” Dr. Kavanaugh commented.
Military physicians tell him they are prescribing a lot of apremilast for armed forces deploying overseas because it’s not immunosuppressive and doesn’t entail laboratory testing.
The research agenda for PDE-4 inhibition in psoriatic disease is extensive, he noted. There is a need for formal studies of PDE-4 inhibition in combination with conventional disease-modifying antirheumatic drugs or biologics. Topical formulations, once-daily dosing, and the possibility that PDE-4 inhibition might be the preferred therapy in patients with certain comorbid conditions, such as chronic obstructive pulmonary disease or a history of recurrent infections, are all topics worthy of study. A biomarker to identify in advance which patients with psoriatic arthritis or psoriasis will attain maximum clinical benefit from apremilast, and in which domains, would be of enormous help to clinicians.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
MAUI, HAWAII – 2017 was a banner year in the field of psoriatic arthritis, marked by a huge bump in the number of publications on the topic along with the approval of three additional drugs, Arthur Kavanaugh, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
“There is a tremendous amount of excitement now in the field of psoriatic arthritis,” observed Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego.
Together with his colleague Eric M. Ruderman, MD, Dr. Kavanaugh highlighted the three new drug approvals for psoriatic arthritis in 2017 – abatacept(Orencia), tofacitinib(Xeljanz), and ixekizumab(Taltz) – and also discussed important recent studies of several drugs already available.
Abatacept
In the pivotal double-blind, phase 3 trial involving 424 psoriatic arthritis patients, roughly 60% with prior exposure to a tumor necrosis factor inhibitor and 60% on concomitant methotrexate, the proportion of patients with at least 20% improvement in the American College of Rheumatology criteria (ACR20) was 39.4% in patients on the selective T-cell costimulation modulator, compared with 22.3% among placebo-treated controls. The benefit on psoriasis lesions was modest, and there was no significant difference between the two study arms in terms of Health Assessment Questionnaire-Disability Index response rates (Ann Rheum Dis. 2017 Sep;76[9]:1550-8).
“I think we could say the effect is modest,” Dr. Kavanaugh said. “The challenge to us still is to identify patients who are going to have a good response, likely the patients with more joint than skin symptoms.”
An attractive feature of the drug is that its safety profile is well known as a result of its extensive track record in treating RA, he added.
Tofacitinib
On the basis of the phase 3 OPAL Beyond (N Engl J Med. 2017 Oct 19;377[16]:1525-36) and OPAL Broaden (N Engl J Med. 2017 Oct 19;377[16]:1537-50) clinical trials, the dose approved by the Food and Drug Administration for psoriatic arthritis was 5 mg b.i.d.. There was a higher ACR20 response rate with 10 mg than 5 mg b.i.d. in OPAL Broaden, but not in OPAL Beyond. And since there was a suggestion of a higher adverse event rate with the 10-mg b.i.d. dosing without unequivocal evidence of superior efficacy, the Food and Drug Administration – which always puts safety first – went with 5 mg b.i.d., Dr. Ruderman explained.
Ixekizumab
In the phase 3, double-blind SPIRIT-P1 trial, featuring 417 biologic-naive psoriatic arthritis patients, the ACR20 response rate at week 24 was 62.1% with the interleukin-17A antagonist at 80 mg given subcutaneously every 2 weeks and 57.9% when dosed every 4 weeks, compared with 57.4% with adalimumab(Humira) at 40 mg every 2 weeks and 30.2% with placebo (Ann Rheum Dis. 2017 Jan;76[1]:79-87). The FDA-approved regimen was a 160-mg loading dose of ixekizumab, followed by 80 mg every 4 weeks.
Dr. Kavanaugh noted that an international team of investigators has identified beta-defensin 2 as an easily measurable biomarker of interleukin-17A–driven skin pathology after evaluating 170 proteins expressed in blood, psoriasis lesions, and nonlesional skin. It was a small study, with eight psoriasis patients and eight healthy controls studied before and after receiving secukinumab(Cosentyx), a monoclonal antibody directed against interleukin-17A (J Allergy Clin Immunol. 2017 Mar;139[3]:923-932.e8). But it’s a study with big potential implications.
“This natural antibiotic compound we make that’s in the skin might be a marker of responsiveness to anti–interleukin-17 therapy. It could help in deciding which patients get which drugs. This needs further study, especially now that we’re using anti–interleukin-17 drugs more now,” the rheumatologist said.
The year 2017 also brought important new studies of several drugs already available for psoriatic arthritis.
Intravenous golimumab (Simponi Aria)
Dr. Kavanaugh was first author of the GO-VIBRANT study, a phase 3, double-blind clinical trial in which 480 biologic-naive psoriatic arthritis patients were randomized to a 30-minute infusion of IV golimumab at 2 mg/kg or placebo at weeks 0, 4, 12, and 20.
The primary endpoint, an ACR20 response at week 14, was achieved in 75.1% of patients on the tumor necrosis factor inhibitor versus 21.8% on placebo. An ACR50 response occurred in 43.6% of patients on IV golimumab, compared with 6.3% on placebo, and a Psoriasis and Area Severity Index 75 skin response was achieved in 59.2% on IV golimumab and 13.6% of controls. At week 24, the IV golimumab group demonstrated significantly less radiographic progression as measured by the total modified Sharp/van der Heijde score. The drug was well tolerated, with no opportunistic infections or tuberculosis, and the infusion reaction rate was below 2% (Arthritis Rheumatol. 2017 Nov;69[11]:2151-61).
Secukinumab
In a recent update of the 606-patient FUTURE 1 trial, secukinumab resulted in clinically meaningful improvement in key patient-reported outcomes at week 24, including global assessment of disease activity, which decreased by a mean of 20.6 and 20 points in patients on 150 and 75 mg, respectively, every 4 weeks, compared with a 7.4-point drop in placebo-treated controls.
Psoriatic arthritis quality of life scores improved by 3.5 and 3.2 points in the two secukinumab arms, compared with 0.4 points in controls. Dermatology Life Quality Index scores improved by 8.8 and 7.9 points, versus 0.7 in controls. Patients on the interleukin-17A inhibitor also showed significantly greater improvement in self-assessments measuring pain and fatigue (Ann Rheum Dis. 2017 Jan;76[1]:203-7).
Apremilast (Otezla)
At the 2018 meeting of the American Academy of Dermatology, Dr. Kavanaugh presented 5-year outcomes of the open-label extension of the 504-patient, phase 3 PALACE-1 trial. In an as-observed analysis, patients on apremilast 30 mg b.i.d. up to week 260 had a 71.7% ACR20 response rate, a 48.6% ACR50 response rate, and a 28.4% ACR70 response. Eighty percent of patients on the oral phosphodiesterase-4 (PDE-4) inhibitor had a dactylitis count of 0, and 54.5% had a Maastricht Ankylosing Spondylitis Enthesitis Score of 0.
In a report from the 219-patient, phase 3B ACTIVE trial, investigators showed that biologic-naive patients randomized to apremilast at 30 mg b.i.d. had a significantly greater ACR20 response as early as week 2, which was the first assessment. At that point, the ACR20 rate was 16.4% with apremilast, compared with 6.4% in placebo-treated controls. The apremilast group also demonstrated significant early improvements in patient-reported outcomes, including the Health Assessment Questionnaire-Disability Index, morning stiffness, and enthesitis severity.
The primary outcome, the ACR20 rate at week 16, was 38.2% with active treatment versus 20.2% in controls (Ann Rheum Dis. 2018 Jan 17. doi: 10.1136/annrheumdis-2017-211568).
“The main advantage of apremilast is safety – and that’s a big advantage,” Dr. Kavanaugh commented.
Military physicians tell him they are prescribing a lot of apremilast for armed forces deploying overseas because it’s not immunosuppressive and doesn’t entail laboratory testing.
The research agenda for PDE-4 inhibition in psoriatic disease is extensive, he noted. There is a need for formal studies of PDE-4 inhibition in combination with conventional disease-modifying antirheumatic drugs or biologics. Topical formulations, once-daily dosing, and the possibility that PDE-4 inhibition might be the preferred therapy in patients with certain comorbid conditions, such as chronic obstructive pulmonary disease or a history of recurrent infections, are all topics worthy of study. A biomarker to identify in advance which patients with psoriatic arthritis or psoriasis will attain maximum clinical benefit from apremilast, and in which domains, would be of enormous help to clinicians.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2018
Psoriatic arthritis treatment: “We’re not doing so well”
MAUI, HAWAII – Two recent Scandinavian studies highlight the considerable room for improvement that exists in psoriatic arthritis outcomes, according to speakers at the 2018 Rheumatology Winter Clinical Symposium.
“We’re not doing so well. I think that in general, ,” declared Arthur Kavanaugh, MD, program director for the symposium and professor of medicine at the University of California, San Diego.
“If you say that MDA is remission, a 23% remission rate is not good enough. And there are some people who are not on treatment. So I think we’re still seeing a lag in psoriatic arthritis. We’re not treating it as aggressively as we are rheumatoid arthritis,” said Dr. Kavanaugh, director of the Center for Innovative Therapy in the university’s division of rheumatology, allergy, and immunology.
“This study was a surprise,” he continued. “I think it’s like rheumatoid arthritis was years ago. If you asked docs how they were doing, they would say, ‘My patients are doing great!’ But then you go to the office and measure the patients and it’s like, ‘Well, not so much.’ ”
Another speaker, Eric M. Ruderman, MD, concurred.
That being said, it’s also clear that rheumatologists aren’t doing as well in managing psoriatic arthritis as dermatologists are with psoriasis, where skin clearance or almost-clear rates unimaginable just a few years ago are now routinely attainable, he added.
“In dermatology they’re getting better and better and better and better with each successive new cytokine target. We’re not. The ACR responses with risankizumab [an investigational anti-interleukin-23 p19 inhibitor] are very much like we saw with the tumor necrosis factor inhibitors. The interleukin-12/23 inhibitor responses are very much like we’ve seen with the interleukin-17 inhibitors. So each successive improvement in getting skin disease under control hasn’t really gotten us very much further with joint disease. I don’t know that we’ve cracked that yet,” Dr. Ruderman said.
Another recent Scandinavian psoriatic arthritis study that particularly impressed Dr. Kavanaugh was a Danish nationwide cohort registry study that shed new light upon the burdens imposed by the disease in terms of societal costs, comorbid conditions, and disability. The subjects were 10,525 Danes with psoriatic arthritis and nearly 21,000 matched general population controls evaluated during the period from 5 years prior to diagnosis of psoriatic arthritis through 10 years after.
The costs were impressive: an average of 10,641 euros more per year per psoriatic arthritis patient, compared with controls, during the 10-year period following diagnosis, with most of the difference attributed to higher health care costs and forgone earnings due to unemployment, early retirement, or receipt of a disability pension.
At the time of their diagnosis, psoriatic arthritis patients had a significantly higher burden of comorbid conditions than did controls, including a 1.7-fold higher likelihood of cardiovascular disease, a 1.73-fold increase in risk for pulmonary disease, a 2.03-fold greater likelihood of infectious diseases, and a 1.94-fold increased risk of hematologic disorders.
Five years prior to diagnosis of psoriatic arthritis, affected individuals were 1.36-fold more likely than were controls to be on a disability pension. At diagnosis, they were 1.6-fold more likely. Ten years after diagnosis of psoriatic arthritis, they were 2.69-fold more likely to be on a disability pension. Indeed, by that point, 21.8% of Danish psoriatic arthritis patients were on disability (Ann Rheum Dis. 2017 Sep;76([9]:1495-1501).
Health care costs began rising steeply at least 3 years prior to diagnosis of psoriatic arthritis, as well.
“We need to do better with our psoriatic arthritis patients. I think this beautiful study is a call to attention for us to make sure that we’re identifying people with psoriatic arthritis as early as we can,” Dr. Kavanaugh said.
As for the treat-to-target approach that has become so widespread in the management of rheumatoid arthritis, it has gained a toehold in the treatment of psoriatic arthritis. Dr. Kavanaugh was a member of an international task force that recently published treat-to-target recommendations for psoriatic arthritis and axial spondyloarthritis (Ann Rheum Dis. 2018 Jan;77[1]:3-17).
The recommendation for defining the target in psoriatic arthritis was to use the DAPSA or MDA. However, this was a controversial recommendation because of the dearth of evidence. It passed with 51.6% of the task force votes and a level of agreement of 7.9 on a 0-10 scale.
Despite the demonstrable room for improvement in psoriatic arthritis treatment outcomes, better times are likely to be coming for affected patients. A record-breaking number of publications on psoriatic arthritis was published in 2017, and three additional drugs received marketing approval for the disease.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
MAUI, HAWAII – Two recent Scandinavian studies highlight the considerable room for improvement that exists in psoriatic arthritis outcomes, according to speakers at the 2018 Rheumatology Winter Clinical Symposium.
“We’re not doing so well. I think that in general, ,” declared Arthur Kavanaugh, MD, program director for the symposium and professor of medicine at the University of California, San Diego.
“If you say that MDA is remission, a 23% remission rate is not good enough. And there are some people who are not on treatment. So I think we’re still seeing a lag in psoriatic arthritis. We’re not treating it as aggressively as we are rheumatoid arthritis,” said Dr. Kavanaugh, director of the Center for Innovative Therapy in the university’s division of rheumatology, allergy, and immunology.
“This study was a surprise,” he continued. “I think it’s like rheumatoid arthritis was years ago. If you asked docs how they were doing, they would say, ‘My patients are doing great!’ But then you go to the office and measure the patients and it’s like, ‘Well, not so much.’ ”
Another speaker, Eric M. Ruderman, MD, concurred.
That being said, it’s also clear that rheumatologists aren’t doing as well in managing psoriatic arthritis as dermatologists are with psoriasis, where skin clearance or almost-clear rates unimaginable just a few years ago are now routinely attainable, he added.
“In dermatology they’re getting better and better and better and better with each successive new cytokine target. We’re not. The ACR responses with risankizumab [an investigational anti-interleukin-23 p19 inhibitor] are very much like we saw with the tumor necrosis factor inhibitors. The interleukin-12/23 inhibitor responses are very much like we’ve seen with the interleukin-17 inhibitors. So each successive improvement in getting skin disease under control hasn’t really gotten us very much further with joint disease. I don’t know that we’ve cracked that yet,” Dr. Ruderman said.
Another recent Scandinavian psoriatic arthritis study that particularly impressed Dr. Kavanaugh was a Danish nationwide cohort registry study that shed new light upon the burdens imposed by the disease in terms of societal costs, comorbid conditions, and disability. The subjects were 10,525 Danes with psoriatic arthritis and nearly 21,000 matched general population controls evaluated during the period from 5 years prior to diagnosis of psoriatic arthritis through 10 years after.
The costs were impressive: an average of 10,641 euros more per year per psoriatic arthritis patient, compared with controls, during the 10-year period following diagnosis, with most of the difference attributed to higher health care costs and forgone earnings due to unemployment, early retirement, or receipt of a disability pension.
At the time of their diagnosis, psoriatic arthritis patients had a significantly higher burden of comorbid conditions than did controls, including a 1.7-fold higher likelihood of cardiovascular disease, a 1.73-fold increase in risk for pulmonary disease, a 2.03-fold greater likelihood of infectious diseases, and a 1.94-fold increased risk of hematologic disorders.
Five years prior to diagnosis of psoriatic arthritis, affected individuals were 1.36-fold more likely than were controls to be on a disability pension. At diagnosis, they were 1.6-fold more likely. Ten years after diagnosis of psoriatic arthritis, they were 2.69-fold more likely to be on a disability pension. Indeed, by that point, 21.8% of Danish psoriatic arthritis patients were on disability (Ann Rheum Dis. 2017 Sep;76([9]:1495-1501).
Health care costs began rising steeply at least 3 years prior to diagnosis of psoriatic arthritis, as well.
“We need to do better with our psoriatic arthritis patients. I think this beautiful study is a call to attention for us to make sure that we’re identifying people with psoriatic arthritis as early as we can,” Dr. Kavanaugh said.
As for the treat-to-target approach that has become so widespread in the management of rheumatoid arthritis, it has gained a toehold in the treatment of psoriatic arthritis. Dr. Kavanaugh was a member of an international task force that recently published treat-to-target recommendations for psoriatic arthritis and axial spondyloarthritis (Ann Rheum Dis. 2018 Jan;77[1]:3-17).
The recommendation for defining the target in psoriatic arthritis was to use the DAPSA or MDA. However, this was a controversial recommendation because of the dearth of evidence. It passed with 51.6% of the task force votes and a level of agreement of 7.9 on a 0-10 scale.
Despite the demonstrable room for improvement in psoriatic arthritis treatment outcomes, better times are likely to be coming for affected patients. A record-breaking number of publications on psoriatic arthritis was published in 2017, and three additional drugs received marketing approval for the disease.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
MAUI, HAWAII – Two recent Scandinavian studies highlight the considerable room for improvement that exists in psoriatic arthritis outcomes, according to speakers at the 2018 Rheumatology Winter Clinical Symposium.
“We’re not doing so well. I think that in general, ,” declared Arthur Kavanaugh, MD, program director for the symposium and professor of medicine at the University of California, San Diego.
“If you say that MDA is remission, a 23% remission rate is not good enough. And there are some people who are not on treatment. So I think we’re still seeing a lag in psoriatic arthritis. We’re not treating it as aggressively as we are rheumatoid arthritis,” said Dr. Kavanaugh, director of the Center for Innovative Therapy in the university’s division of rheumatology, allergy, and immunology.
“This study was a surprise,” he continued. “I think it’s like rheumatoid arthritis was years ago. If you asked docs how they were doing, they would say, ‘My patients are doing great!’ But then you go to the office and measure the patients and it’s like, ‘Well, not so much.’ ”
Another speaker, Eric M. Ruderman, MD, concurred.
That being said, it’s also clear that rheumatologists aren’t doing as well in managing psoriatic arthritis as dermatologists are with psoriasis, where skin clearance or almost-clear rates unimaginable just a few years ago are now routinely attainable, he added.
“In dermatology they’re getting better and better and better and better with each successive new cytokine target. We’re not. The ACR responses with risankizumab [an investigational anti-interleukin-23 p19 inhibitor] are very much like we saw with the tumor necrosis factor inhibitors. The interleukin-12/23 inhibitor responses are very much like we’ve seen with the interleukin-17 inhibitors. So each successive improvement in getting skin disease under control hasn’t really gotten us very much further with joint disease. I don’t know that we’ve cracked that yet,” Dr. Ruderman said.
Another recent Scandinavian psoriatic arthritis study that particularly impressed Dr. Kavanaugh was a Danish nationwide cohort registry study that shed new light upon the burdens imposed by the disease in terms of societal costs, comorbid conditions, and disability. The subjects were 10,525 Danes with psoriatic arthritis and nearly 21,000 matched general population controls evaluated during the period from 5 years prior to diagnosis of psoriatic arthritis through 10 years after.
The costs were impressive: an average of 10,641 euros more per year per psoriatic arthritis patient, compared with controls, during the 10-year period following diagnosis, with most of the difference attributed to higher health care costs and forgone earnings due to unemployment, early retirement, or receipt of a disability pension.
At the time of their diagnosis, psoriatic arthritis patients had a significantly higher burden of comorbid conditions than did controls, including a 1.7-fold higher likelihood of cardiovascular disease, a 1.73-fold increase in risk for pulmonary disease, a 2.03-fold greater likelihood of infectious diseases, and a 1.94-fold increased risk of hematologic disorders.
Five years prior to diagnosis of psoriatic arthritis, affected individuals were 1.36-fold more likely than were controls to be on a disability pension. At diagnosis, they were 1.6-fold more likely. Ten years after diagnosis of psoriatic arthritis, they were 2.69-fold more likely to be on a disability pension. Indeed, by that point, 21.8% of Danish psoriatic arthritis patients were on disability (Ann Rheum Dis. 2017 Sep;76([9]:1495-1501).
Health care costs began rising steeply at least 3 years prior to diagnosis of psoriatic arthritis, as well.
“We need to do better with our psoriatic arthritis patients. I think this beautiful study is a call to attention for us to make sure that we’re identifying people with psoriatic arthritis as early as we can,” Dr. Kavanaugh said.
As for the treat-to-target approach that has become so widespread in the management of rheumatoid arthritis, it has gained a toehold in the treatment of psoriatic arthritis. Dr. Kavanaugh was a member of an international task force that recently published treat-to-target recommendations for psoriatic arthritis and axial spondyloarthritis (Ann Rheum Dis. 2018 Jan;77[1]:3-17).
The recommendation for defining the target in psoriatic arthritis was to use the DAPSA or MDA. However, this was a controversial recommendation because of the dearth of evidence. It passed with 51.6% of the task force votes and a level of agreement of 7.9 on a 0-10 scale.
Despite the demonstrable room for improvement in psoriatic arthritis treatment outcomes, better times are likely to be coming for affected patients. A record-breaking number of publications on psoriatic arthritis was published in 2017, and three additional drugs received marketing approval for the disease.
Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2018
Young diabetics are at sevenfold increased risk of sudden cardiac death
ANAHEIM, CALIF. – Children and young adults with type 1 or type 2 diabetes have a 7.4-fold increased risk of sudden cardiac death, compared with nondiabetic, age-matched controls, according to a first-of-its-kind Danish national study.
“Luckily the absolute risk is low, but we hope these data will make [young patients with diabetes] think more about taking their insulin and following their physicians’ recommendations about treatment,” Jesper Svane said in presenting the study findings at the American Heart Association scientific sessions.
Sudden cardiac death (SCD) was the No. 1 cause of mortality in the diabetic cohort with a rate of 34.8 deaths/100,000 person-years, compared with 4.7 deaths/100,000 person-years in an age-matched nondiabetic cohort. That translates to a 7.4-fold increased risk of SCD in the diabetic cohort, noted Mr. Svane, a medical student at Copenhagen University.
When deaths caused by SCD were combined with those from other cardiac diseases, the young diabetic cohort had a rate of 68.3 deaths/100,000 person-years versus 8.2 deaths/100,000 person-years in age-matched controls, for an 8.3-fold increased risk. This observation underscores an important point: Monitoring cardiovascular risk needs to start early in young patients with diabetes.
“It’s important to pay attention when a young person with diabetes comes in complaining of chest pain or syncope,” Mr. Svane said.
The second and third most common causes of death in young Danish diabetic patients were pulmonary and endocrine diseases, which occurred at rates 7.2- and 79.2-fold greater in these patients, respectively, than in controls.
All-cause mortality occurred at a rate of 234.9 deaths/100,000 person-years in young patients with diabetes versus 50.9 deaths/100,000 person-years in matched controls, for a 4.6-fold increased risk.
Autopsies showed that the most common cause of death in diabetic persons aged 36-49 years was coronary artery disease, while in those up to age 35, it was sudden arrhythmic death syndrome, a label bestowed when a medical examiner can’t find an apparent cause of death.
Session moderator Robert H. Eckle, MD, a past AHA president, cautioned against routinely attributing the deaths without apparent cause at autopsy in young people with diabetes to sudden arrhythmic death syndrome. Given that the Danish registry data don’t include data on diabetic patients’ degree of metabolic control, it seems likely that an uncertain number of those deaths were really caused by hypoglycemia, observed Dr. Eckle, professor of medicine at the University of Colorado at Denver, Aurora.
Mr. Svane reported having no financial conflicts of interest.
SOURCE: Svane J. 2017 AHA Sessions.
ANAHEIM, CALIF. – Children and young adults with type 1 or type 2 diabetes have a 7.4-fold increased risk of sudden cardiac death, compared with nondiabetic, age-matched controls, according to a first-of-its-kind Danish national study.
“Luckily the absolute risk is low, but we hope these data will make [young patients with diabetes] think more about taking their insulin and following their physicians’ recommendations about treatment,” Jesper Svane said in presenting the study findings at the American Heart Association scientific sessions.
Sudden cardiac death (SCD) was the No. 1 cause of mortality in the diabetic cohort with a rate of 34.8 deaths/100,000 person-years, compared with 4.7 deaths/100,000 person-years in an age-matched nondiabetic cohort. That translates to a 7.4-fold increased risk of SCD in the diabetic cohort, noted Mr. Svane, a medical student at Copenhagen University.
When deaths caused by SCD were combined with those from other cardiac diseases, the young diabetic cohort had a rate of 68.3 deaths/100,000 person-years versus 8.2 deaths/100,000 person-years in age-matched controls, for an 8.3-fold increased risk. This observation underscores an important point: Monitoring cardiovascular risk needs to start early in young patients with diabetes.
“It’s important to pay attention when a young person with diabetes comes in complaining of chest pain or syncope,” Mr. Svane said.
The second and third most common causes of death in young Danish diabetic patients were pulmonary and endocrine diseases, which occurred at rates 7.2- and 79.2-fold greater in these patients, respectively, than in controls.
All-cause mortality occurred at a rate of 234.9 deaths/100,000 person-years in young patients with diabetes versus 50.9 deaths/100,000 person-years in matched controls, for a 4.6-fold increased risk.
Autopsies showed that the most common cause of death in diabetic persons aged 36-49 years was coronary artery disease, while in those up to age 35, it was sudden arrhythmic death syndrome, a label bestowed when a medical examiner can’t find an apparent cause of death.
Session moderator Robert H. Eckle, MD, a past AHA president, cautioned against routinely attributing the deaths without apparent cause at autopsy in young people with diabetes to sudden arrhythmic death syndrome. Given that the Danish registry data don’t include data on diabetic patients’ degree of metabolic control, it seems likely that an uncertain number of those deaths were really caused by hypoglycemia, observed Dr. Eckle, professor of medicine at the University of Colorado at Denver, Aurora.
Mr. Svane reported having no financial conflicts of interest.
SOURCE: Svane J. 2017 AHA Sessions.
ANAHEIM, CALIF. – Children and young adults with type 1 or type 2 diabetes have a 7.4-fold increased risk of sudden cardiac death, compared with nondiabetic, age-matched controls, according to a first-of-its-kind Danish national study.
“Luckily the absolute risk is low, but we hope these data will make [young patients with diabetes] think more about taking their insulin and following their physicians’ recommendations about treatment,” Jesper Svane said in presenting the study findings at the American Heart Association scientific sessions.
Sudden cardiac death (SCD) was the No. 1 cause of mortality in the diabetic cohort with a rate of 34.8 deaths/100,000 person-years, compared with 4.7 deaths/100,000 person-years in an age-matched nondiabetic cohort. That translates to a 7.4-fold increased risk of SCD in the diabetic cohort, noted Mr. Svane, a medical student at Copenhagen University.
When deaths caused by SCD were combined with those from other cardiac diseases, the young diabetic cohort had a rate of 68.3 deaths/100,000 person-years versus 8.2 deaths/100,000 person-years in age-matched controls, for an 8.3-fold increased risk. This observation underscores an important point: Monitoring cardiovascular risk needs to start early in young patients with diabetes.
“It’s important to pay attention when a young person with diabetes comes in complaining of chest pain or syncope,” Mr. Svane said.
The second and third most common causes of death in young Danish diabetic patients were pulmonary and endocrine diseases, which occurred at rates 7.2- and 79.2-fold greater in these patients, respectively, than in controls.
All-cause mortality occurred at a rate of 234.9 deaths/100,000 person-years in young patients with diabetes versus 50.9 deaths/100,000 person-years in matched controls, for a 4.6-fold increased risk.
Autopsies showed that the most common cause of death in diabetic persons aged 36-49 years was coronary artery disease, while in those up to age 35, it was sudden arrhythmic death syndrome, a label bestowed when a medical examiner can’t find an apparent cause of death.
Session moderator Robert H. Eckle, MD, a past AHA president, cautioned against routinely attributing the deaths without apparent cause at autopsy in young people with diabetes to sudden arrhythmic death syndrome. Given that the Danish registry data don’t include data on diabetic patients’ degree of metabolic control, it seems likely that an uncertain number of those deaths were really caused by hypoglycemia, observed Dr. Eckle, professor of medicine at the University of Colorado at Denver, Aurora.
Mr. Svane reported having no financial conflicts of interest.
SOURCE: Svane J. 2017 AHA Sessions.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: Young persons with diabetes are 8.3-fold more likely to die of cardiac causes.
Major finding: In particular, the risk of sudden cardiac death in Danish children and young adults with diabetes was 7.4-fold greater than in age-matched controls.
Study details: This was a Danish national registry study of more than 14,000 children and young adults with diabetes and their rate of sudden cardiac death.
Disclosures: The study presenter reported having no financial conflicts.
Source: Svane J. 2017 AHA Sessions.
Bloating. Flatulence. Think SIBO
MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.
There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.
The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.
So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.
SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.
The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.
“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”
First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.
“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.
Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.
“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.
Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.
“A lot of our cirrhotic patients are on both,” she noted.
Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.
Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.
“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.
FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).
“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.
Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.
“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.
MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.
There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.
The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.
So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.
SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.
The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.
“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”
First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.
“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.
Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.
“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.
Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.
“A lot of our cirrhotic patients are on both,” she noted.
Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.
Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.
“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.
FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).
“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.
Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.
“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.
MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.
“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.
There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.
The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.
So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.
SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.
The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.
“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”
First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.
“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.
Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.
“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.
Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.
“A lot of our cirrhotic patients are on both,” she noted.
Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.
Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.
“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.
FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).
“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.
Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.
“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.
EXPERT ANALYSIS FROM RWCS 2018
Mild cognitive impairment rises in heart patients with comorbidities
ANAHEIM, CALIF. – Across the spectrum of cardiovascular disease, the more comorbid conditions a patient has, the higher the likelihood of mild cognitive impairment, Jocasta Ball, PhD, reported at the American Heart Association scientific sessions.
Indeed, her cross-sectional analysis of baseline data on 2,161 participants in five randomized controlled trials of nurse-led chronic disease management in cardiovascular disease (CVD) showed that for every 1-unit increase in the age-adjusted Charlson Comorbidity Index, the likelihood of mild cognitive impairment (MCI) jumped by 19%.
This novel observation has important clinical implications: “MCI is becoming increasingly recognized as exerting a powerful and negative impact on the risk, management, and prognosis of CVD patients,” explained Dr. Ball of the Baker Heart and Diabetes Institute in Melbourne. “Because MCI undermines a patient’s ability to comply with medical treatment and adds to patient complexity, it is critical [to identify] higher-risk individuals who require closer surveillance and improved early intervention.”
She added that the findings open up a whole new field of research aimed at developing new interventions to help patients with CVD and MCI stay on track with their heart disease treatment program.
The 2,161 subjects, mean age 70 years and two-thirds male, ranged across the full spectrum of cardiovascular disease, from mild to severe. All were screened for MCI by completing the Montreal Cognitive Assessment, or MoCA. A MoCA score below 26 out of a possible 30 is defined as MCI.
Forty-seven percent of subjects had MCI. They were older, with a mean age of 73 years versus 67 years; were more likely to have a history of stroke, by a margin of 20% versus 12%; had a 52% prevalence of atrial fibrillation versus 44%; and had a 50% prevalence of heart failure versus 39% in subjects with normal cognition. In addition, 48% of the MCI group screened positive for depressive symptoms versus 37% of those without MCI, and 28% of patients with MCI had type 2 diabetes, compared with 22% of those without MCI. Renal disease was also significantly more prevalent in the MCI group, by a margin of 21% versus 14%.
In a multivariate regression analysis, the strongest predictors of MCI in patients across the spectrum of CVD were current smoking, with a 2.5-fold increased risk compared with that of nonsmokers, and atrial fibrillation, with a 1.3-fold increased risk.
Dr. Ball reported having no financial conflicts regarding her study.
SOURCE: Ball J. et al. AHA 2017, Abstract 16240.
ANAHEIM, CALIF. – Across the spectrum of cardiovascular disease, the more comorbid conditions a patient has, the higher the likelihood of mild cognitive impairment, Jocasta Ball, PhD, reported at the American Heart Association scientific sessions.
Indeed, her cross-sectional analysis of baseline data on 2,161 participants in five randomized controlled trials of nurse-led chronic disease management in cardiovascular disease (CVD) showed that for every 1-unit increase in the age-adjusted Charlson Comorbidity Index, the likelihood of mild cognitive impairment (MCI) jumped by 19%.
This novel observation has important clinical implications: “MCI is becoming increasingly recognized as exerting a powerful and negative impact on the risk, management, and prognosis of CVD patients,” explained Dr. Ball of the Baker Heart and Diabetes Institute in Melbourne. “Because MCI undermines a patient’s ability to comply with medical treatment and adds to patient complexity, it is critical [to identify] higher-risk individuals who require closer surveillance and improved early intervention.”
She added that the findings open up a whole new field of research aimed at developing new interventions to help patients with CVD and MCI stay on track with their heart disease treatment program.
The 2,161 subjects, mean age 70 years and two-thirds male, ranged across the full spectrum of cardiovascular disease, from mild to severe. All were screened for MCI by completing the Montreal Cognitive Assessment, or MoCA. A MoCA score below 26 out of a possible 30 is defined as MCI.
Forty-seven percent of subjects had MCI. They were older, with a mean age of 73 years versus 67 years; were more likely to have a history of stroke, by a margin of 20% versus 12%; had a 52% prevalence of atrial fibrillation versus 44%; and had a 50% prevalence of heart failure versus 39% in subjects with normal cognition. In addition, 48% of the MCI group screened positive for depressive symptoms versus 37% of those without MCI, and 28% of patients with MCI had type 2 diabetes, compared with 22% of those without MCI. Renal disease was also significantly more prevalent in the MCI group, by a margin of 21% versus 14%.
In a multivariate regression analysis, the strongest predictors of MCI in patients across the spectrum of CVD were current smoking, with a 2.5-fold increased risk compared with that of nonsmokers, and atrial fibrillation, with a 1.3-fold increased risk.
Dr. Ball reported having no financial conflicts regarding her study.
SOURCE: Ball J. et al. AHA 2017, Abstract 16240.
ANAHEIM, CALIF. – Across the spectrum of cardiovascular disease, the more comorbid conditions a patient has, the higher the likelihood of mild cognitive impairment, Jocasta Ball, PhD, reported at the American Heart Association scientific sessions.
Indeed, her cross-sectional analysis of baseline data on 2,161 participants in five randomized controlled trials of nurse-led chronic disease management in cardiovascular disease (CVD) showed that for every 1-unit increase in the age-adjusted Charlson Comorbidity Index, the likelihood of mild cognitive impairment (MCI) jumped by 19%.
This novel observation has important clinical implications: “MCI is becoming increasingly recognized as exerting a powerful and negative impact on the risk, management, and prognosis of CVD patients,” explained Dr. Ball of the Baker Heart and Diabetes Institute in Melbourne. “Because MCI undermines a patient’s ability to comply with medical treatment and adds to patient complexity, it is critical [to identify] higher-risk individuals who require closer surveillance and improved early intervention.”
She added that the findings open up a whole new field of research aimed at developing new interventions to help patients with CVD and MCI stay on track with their heart disease treatment program.
The 2,161 subjects, mean age 70 years and two-thirds male, ranged across the full spectrum of cardiovascular disease, from mild to severe. All were screened for MCI by completing the Montreal Cognitive Assessment, or MoCA. A MoCA score below 26 out of a possible 30 is defined as MCI.
Forty-seven percent of subjects had MCI. They were older, with a mean age of 73 years versus 67 years; were more likely to have a history of stroke, by a margin of 20% versus 12%; had a 52% prevalence of atrial fibrillation versus 44%; and had a 50% prevalence of heart failure versus 39% in subjects with normal cognition. In addition, 48% of the MCI group screened positive for depressive symptoms versus 37% of those without MCI, and 28% of patients with MCI had type 2 diabetes, compared with 22% of those without MCI. Renal disease was also significantly more prevalent in the MCI group, by a margin of 21% versus 14%.
In a multivariate regression analysis, the strongest predictors of MCI in patients across the spectrum of CVD were current smoking, with a 2.5-fold increased risk compared with that of nonsmokers, and atrial fibrillation, with a 1.3-fold increased risk.
Dr. Ball reported having no financial conflicts regarding her study.
SOURCE: Ball J. et al. AHA 2017, Abstract 16240.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: The more comorbid conditions a patient with cardiovascular disease has, the greater the likelihood of mild cognitive impairment becomes.
Major finding: For each 1-unit increase in the Charlson Comorbidity Index, the likelihood of prevalent mild cognitive impairment rose by 19%.
Study details: This cross-sectional study assessed the association between mild cognitive impairment and Charlson Comorbidity Index score in 2,161 patients with cardiovascular disease of varied degrees of severity.
Disclosures: The presenter reported having no financial conflicts regarding her study.
Source: Ball J et al. AHA 2017, Abstract 16240
Aspirin may protect against dementia in T2DM
ANAHEIM, CALIF. – in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.
The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.
JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.
In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.
During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.
JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).
Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.
She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.
Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”
Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.
Dr. Matsumoto reported having no financial conflicts.
SOURCE: Matsumoto C. AHA scientific sessions.
ANAHEIM, CALIF. – in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.
The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.
JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.
In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.
During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.
JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).
Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.
She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.
Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”
Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.
Dr. Matsumoto reported having no financial conflicts.
SOURCE: Matsumoto C. AHA scientific sessions.
ANAHEIM, CALIF. – in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.
The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.
JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.
In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.
During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.
JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).
Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.
She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.
Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”
Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.
Dr. Matsumoto reported having no financial conflicts.
SOURCE: Matsumoto C. AHA scientific sessions.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Daily low-dose aspirin reduced the incidence of dementia by more than one-third in patients with type 2 diabetes.
Study details: A multicenter randomized prospective cohort study of 2,536 patients with type 2 diabetes.
Disclosures: The study presenter reported having no financial conflicts.
Source: Matsumoto C. AHA scientific sessions.
Adding hypertension in pregnancy doesn’t refine ASCVD risk prediction tool
ANAHEIM, CALIF. – The first-ever study to examine the clinical utility of incorporating a history of hypertensive disorders of pregnancy into the American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Calculator in an effort to better delineate risk in women failed to show any added benefit.
But that doesn’t mean such a history is without value in daily clinical practice, Jennifer J. Stuart, ScD, asserted at the American Heart Association scientific sessions.
“While we did not demonstrate that hypertensive disorders of pregnancy improved cardiovascular risk discrimination in women, we do still believe – and I still believe – that hypertensive disorders of pregnancy remain an important risk marker for cardiovascular disease in women,” said Dr. Stuart of the Harvard School of Public Health, Boston.
“In this latest analysis we’ve demonstrated over a fourfold increased risk of chronic hypertension in these women in the first 5 years after delivery. So we do see increased risk very soon after delivery, and it persists for decades. And hypertensive disorders of pregnancy as a risk marker does offer practical advantages: ease of ascertainment, low cost, and availability earlier in life,” the researcher noted.
Her study hypothesis was that adding hypertensive disorders of pregnancy – that is, gestational hypertension and preeclampsia – and parity to the current ACC/AHA ASCVD Risk Calculator would enhance the tool’s predictive tool’s power in women.
“We wanted to know if a history of hypertensive disorders of pregnancy can be leveraged to capture women currently being missed in screening,” she explained.
Her expectation that this would be the case was based on solid evidence that hypertensive disorders of pregnancy, which occur in 10%-15% of all pregnancies, are associated with subsequent increased risk of cardiovascular events. For example, a meta-analysis of published studies involving nearly 3.5 million women, including almost 200,000 with a history of preeclampsia, showed that preeclampsia was associated with a 2.16-fold increased risk of ischemic heart disease during 11.7 years of follow-up (BMJ. 2007 Nov 10;335[7627]:974). This meta-analysis was among the evidence that persuaded the AHA in 2011 to formally add hypertensive disorders of pregnancy to the list of risk factors for cardiovascular disease in women (Circulation. 2011 Mar 22;123[11]:1243-62).
Dr. Stuart also incorporated parity in her investigational revised ASCVD risk model, because parity has been shown to be an independent risk factor of cardiovascular disease in a relationship described by a J-shaped curve.
She put the souped-up risk prediction model to the test by separately applying it and the current version to data from the longitudinal prospective Nurses’ Health Study II. For this analysis, nearly 68,000 female registered nurses were followed for new diseases every 2 years from 1989, when they were aged 25-42, through 2013. She and her coinvestigators applied the two 10-year risk-prediction models to the overall cohort and again separately to women at aged 40-49 and 50-59.
The bottom line: This might be because the nurses comprise a relatively low-risk population. Also, even though hypertensive disorders of pregnancy are associated with 10-year cardiovascular disease risk independent of the established risk factors, there may be enough overlap that the standard risk factors sufficiently capture the risk.
“It may be that the information on history of hypertensive disorders of pregnancy should be ascertained in the 20s and 30s, rather than waiting until age 40 or later, when we generally apply cardiovascular risk scores in practice. That [earlier assessment] may be a really important and valuable opportunity to identify these women at high risk and utilize primary prevention,” according to Dr. Stuart.
What’s next? “I’m certainly interested in educating these women about their increased risk. This is not something that’s done consistently across the country and across practices, and we really believe this is an important message for women to get when they deliver these pregnancies,” she added.
Dr. Stuart reported having no financial conflicts of interest regarding her study.
SOURCE: Stuart JJ. AHA Scientific Sessions.
ANAHEIM, CALIF. – The first-ever study to examine the clinical utility of incorporating a history of hypertensive disorders of pregnancy into the American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Calculator in an effort to better delineate risk in women failed to show any added benefit.
But that doesn’t mean such a history is without value in daily clinical practice, Jennifer J. Stuart, ScD, asserted at the American Heart Association scientific sessions.
“While we did not demonstrate that hypertensive disorders of pregnancy improved cardiovascular risk discrimination in women, we do still believe – and I still believe – that hypertensive disorders of pregnancy remain an important risk marker for cardiovascular disease in women,” said Dr. Stuart of the Harvard School of Public Health, Boston.
“In this latest analysis we’ve demonstrated over a fourfold increased risk of chronic hypertension in these women in the first 5 years after delivery. So we do see increased risk very soon after delivery, and it persists for decades. And hypertensive disorders of pregnancy as a risk marker does offer practical advantages: ease of ascertainment, low cost, and availability earlier in life,” the researcher noted.
Her study hypothesis was that adding hypertensive disorders of pregnancy – that is, gestational hypertension and preeclampsia – and parity to the current ACC/AHA ASCVD Risk Calculator would enhance the tool’s predictive tool’s power in women.
“We wanted to know if a history of hypertensive disorders of pregnancy can be leveraged to capture women currently being missed in screening,” she explained.
Her expectation that this would be the case was based on solid evidence that hypertensive disorders of pregnancy, which occur in 10%-15% of all pregnancies, are associated with subsequent increased risk of cardiovascular events. For example, a meta-analysis of published studies involving nearly 3.5 million women, including almost 200,000 with a history of preeclampsia, showed that preeclampsia was associated with a 2.16-fold increased risk of ischemic heart disease during 11.7 years of follow-up (BMJ. 2007 Nov 10;335[7627]:974). This meta-analysis was among the evidence that persuaded the AHA in 2011 to formally add hypertensive disorders of pregnancy to the list of risk factors for cardiovascular disease in women (Circulation. 2011 Mar 22;123[11]:1243-62).
Dr. Stuart also incorporated parity in her investigational revised ASCVD risk model, because parity has been shown to be an independent risk factor of cardiovascular disease in a relationship described by a J-shaped curve.
She put the souped-up risk prediction model to the test by separately applying it and the current version to data from the longitudinal prospective Nurses’ Health Study II. For this analysis, nearly 68,000 female registered nurses were followed for new diseases every 2 years from 1989, when they were aged 25-42, through 2013. She and her coinvestigators applied the two 10-year risk-prediction models to the overall cohort and again separately to women at aged 40-49 and 50-59.
The bottom line: This might be because the nurses comprise a relatively low-risk population. Also, even though hypertensive disorders of pregnancy are associated with 10-year cardiovascular disease risk independent of the established risk factors, there may be enough overlap that the standard risk factors sufficiently capture the risk.
“It may be that the information on history of hypertensive disorders of pregnancy should be ascertained in the 20s and 30s, rather than waiting until age 40 or later, when we generally apply cardiovascular risk scores in practice. That [earlier assessment] may be a really important and valuable opportunity to identify these women at high risk and utilize primary prevention,” according to Dr. Stuart.
What’s next? “I’m certainly interested in educating these women about their increased risk. This is not something that’s done consistently across the country and across practices, and we really believe this is an important message for women to get when they deliver these pregnancies,” she added.
Dr. Stuart reported having no financial conflicts of interest regarding her study.
SOURCE: Stuart JJ. AHA Scientific Sessions.
ANAHEIM, CALIF. – The first-ever study to examine the clinical utility of incorporating a history of hypertensive disorders of pregnancy into the American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Calculator in an effort to better delineate risk in women failed to show any added benefit.
But that doesn’t mean such a history is without value in daily clinical practice, Jennifer J. Stuart, ScD, asserted at the American Heart Association scientific sessions.
“While we did not demonstrate that hypertensive disorders of pregnancy improved cardiovascular risk discrimination in women, we do still believe – and I still believe – that hypertensive disorders of pregnancy remain an important risk marker for cardiovascular disease in women,” said Dr. Stuart of the Harvard School of Public Health, Boston.
“In this latest analysis we’ve demonstrated over a fourfold increased risk of chronic hypertension in these women in the first 5 years after delivery. So we do see increased risk very soon after delivery, and it persists for decades. And hypertensive disorders of pregnancy as a risk marker does offer practical advantages: ease of ascertainment, low cost, and availability earlier in life,” the researcher noted.
Her study hypothesis was that adding hypertensive disorders of pregnancy – that is, gestational hypertension and preeclampsia – and parity to the current ACC/AHA ASCVD Risk Calculator would enhance the tool’s predictive tool’s power in women.
“We wanted to know if a history of hypertensive disorders of pregnancy can be leveraged to capture women currently being missed in screening,” she explained.
Her expectation that this would be the case was based on solid evidence that hypertensive disorders of pregnancy, which occur in 10%-15% of all pregnancies, are associated with subsequent increased risk of cardiovascular events. For example, a meta-analysis of published studies involving nearly 3.5 million women, including almost 200,000 with a history of preeclampsia, showed that preeclampsia was associated with a 2.16-fold increased risk of ischemic heart disease during 11.7 years of follow-up (BMJ. 2007 Nov 10;335[7627]:974). This meta-analysis was among the evidence that persuaded the AHA in 2011 to formally add hypertensive disorders of pregnancy to the list of risk factors for cardiovascular disease in women (Circulation. 2011 Mar 22;123[11]:1243-62).
Dr. Stuart also incorporated parity in her investigational revised ASCVD risk model, because parity has been shown to be an independent risk factor of cardiovascular disease in a relationship described by a J-shaped curve.
She put the souped-up risk prediction model to the test by separately applying it and the current version to data from the longitudinal prospective Nurses’ Health Study II. For this analysis, nearly 68,000 female registered nurses were followed for new diseases every 2 years from 1989, when they were aged 25-42, through 2013. She and her coinvestigators applied the two 10-year risk-prediction models to the overall cohort and again separately to women at aged 40-49 and 50-59.
The bottom line: This might be because the nurses comprise a relatively low-risk population. Also, even though hypertensive disorders of pregnancy are associated with 10-year cardiovascular disease risk independent of the established risk factors, there may be enough overlap that the standard risk factors sufficiently capture the risk.
“It may be that the information on history of hypertensive disorders of pregnancy should be ascertained in the 20s and 30s, rather than waiting until age 40 or later, when we generally apply cardiovascular risk scores in practice. That [earlier assessment] may be a really important and valuable opportunity to identify these women at high risk and utilize primary prevention,” according to Dr. Stuart.
What’s next? “I’m certainly interested in educating these women about their increased risk. This is not something that’s done consistently across the country and across practices, and we really believe this is an important message for women to get when they deliver these pregnancies,” she added.
Dr. Stuart reported having no financial conflicts of interest regarding her study.
SOURCE: Stuart JJ. AHA Scientific Sessions.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: The ACC/AHA Atherosclerotic Cardiovascular Disease Risk Calculator doesn’t do a better job of predicting 10-year risk in women when a history of hypertensive disorders of pregnancy is added into the formula.
Major finding: Incorporating a woman’s history of hypertensive disorders of pregnancy into the Atherosclerotic Cardiovascular Disease Risk Calculator doesn’t improve the tool’s accuracy in predicting 10-year risk.
Study details: An analysis of data from the longitudinal, prospective Nurses’ Health Study II.
Disclosures: The study presenter reported having no financial conflicts of interest.
Source: Stuart JJ. AHA Scientific Sessions.
Mast cell synovitis: potential target in RA?
MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?
Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm2 at baseline to 8.2/mm2 at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.
Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.
In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.
His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.
“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.
Dr. Troum reported having no financial conflicts regarding his presentation.
MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?
Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm2 at baseline to 8.2/mm2 at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.
Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.
In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.
His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.
“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.
Dr. Troum reported having no financial conflicts regarding his presentation.
MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?
Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm2 at baseline to 8.2/mm2 at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.
Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.
In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.
His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.
“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.
Dr. Troum reported having no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM RWCS 2018