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Mitchel is a reporter for MDedge based in the Philadelphia area. He started with the company in 1992, when it was International Medical News Group (IMNG), and has since covered a range of medical specialties. Mitchel trained as a virologist at Roswell Park Memorial Institute in Buffalo, and then worked briefly as a researcher at Boston Children's Hospital before pivoting to journalism as a AAAS Mass Media Fellow in 1980. His first reporting job was with Science Digest magazine, and from the mid-1980s to early-1990s he was a reporter with Medical World News. @mitchelzoler
FDA approves cangrelor, an intravenous antiplatelet drug
Cangrelor became the first intravenous antiplatelet agent acting on ADP receptors for adult patients undergoing percutaneous coronary intervention to receive marketing approval from the Food and Drug Administration, The Medicines Company announced on June 22.
While cangrelor’s unique delivery route and rapid onset and off-set of action set it apart and may give it certain clinical advantages over the three approved oral drugs that target the same platelet receptor – clopidogrel, prasugrel (Effient), and ticagrelor (Brilinta) – cangrelor will also be distinguished by its much higher price. The standard dosage to treat one patient undergoing percutaneous coronary intervention (PCI) with cangrelor (Kengreal) will have a wholesale acquisition cost of $749, Raymond Russo, senior vice president of The Medicines Company, said at a June 23 press briefing. That prices cangrelor substantially above its brand-name competition, which costs roughly $10 for similar treatment, as well as generic clopidogrel, which costs about $3 for the same indication.
“I believe in the strength of the data that showed that cangrelor was superior to the comparator drug [clopidogrel], and if cost were not an issue I’d use cangrelor routinely, but I am not naive; cost is an issue,” said Dr. Deepak L. Bhatt, professor of medicine at Harvard University and executive director of interventional cardiology programs at Brigham and Women’s Hospital in Boston, and co–lead investigator for the CHAMPION PHOENIX pivotal trial that led to cangrelor’s approval (N. Engl. J. Med. 2013;368:1303-13).
Whether or not interventional cardiologists and the centers where they work decide to use cangrelor or one of the oral antiplatelet drugs for coronary artery disease (CAD) patients undergoing PCI will likely depend on a series of considerations that will need to take into account not just drug cost but also practice strategies, a patient’s clinical state, and the potential for ancillary costs from following an entirely different management approach.
The first issue is whether the interventionalist decides to pretreat a patient scheduled for angioplasty and possible immediate PCI following angiography with an ADP-receptor antagonist (also known as a P2Y12-receptor inhibitor) prior to the start of angiography or opts to defer that treatment until the angiography results are available and a decision is made to proceed with PCI. Recent nationwide registry data suggest that roughly half of U.S. interventionalists treat their patients upfront with an ADP-receptor antagonist, usually clopidogrel for patients with stable angina or prasugrel or ticagrelor if they have either a non-ST-elevation MI or a ST-elevation MI, while the other 50% of interventionalists will wait to administer the ADP-receptor antagonist until angiography is complete, Dr. Bhatt explained in an interview.
The advantage to upfront treatment is that by the time the patient is ready for PCI an oral ADP-receptor antagonist is fully absorbed and on board. The disadvantage is that if the coronary anatomy demands a surgical approach to revascularization many surgeons would elect not to operate on a patient freshly dosed with an antiplatelet agent, and these patients often remain hospitalized for several days until the ADP-receptor antagonist clears and the patient’s platelet function returns to normal. Angiography generally identifies 10%-15% of these patients with a CAD distribution that necessitates surgical coronary bypass, and the potential hospitalization expense of waiting for their ADP-receptor antagonist to clear could be a major cost to counterbalance the price of cangrelor, which would obviate this expense if the quick-to-start-and-to-clear cangrelor were used instead of a more lumbering oral drug, he noted.
The other 50% of U.S. interventionalists, Dr. Bhatt included, take a different approach. Recognizing the potential downside of upfront oral antiplatelet therapy if the patient is pegged for bypass surgery following angiography, they elect to wait until the angiography results are in hand. If the angiography results show the patient is destined for surgery or for medical management, then the patient receives no ADP-receptor antagonist. The cardiologist administers an ADP-receptor antagonist only if the patient’s CAD is appropriate for PCI, the fate for most of these CAD patients following angiography. It’s under these circumstances that the advantages of cangrelor kick in, as shown in the results from CHAMPION PHOENIX.
This trial randomized patients to two different types of ADP-receptor antagonist treatment while they were in the coronary catheterization laboratory. The study results showed a statistically significant, 22% relative-risk reduction in the primary endpoint in favor of intravenous cangrelor compared with oral clopidogrel delivered while patients were “on the table” in the interval between angiography and PCI. That 22% relative improvement in outcomes, driven primarily by reductions in periprocedural MIs and stent thrombosis, improved to a 31% relative-risk reduction when The Medicines Company performed a new analysis of the study results at the FDA’s request using a more stringent and conventional definition of periprocedural MIs and stent thrombosis. The time needed to perform this and other FDA-requested analyses largely caused the greater than 2-year gap between the 2013 publication of the CHAMPION PHOENIX results and the FDA’s approval.
But the editorial that accompanied the 2013 publication highlighted what the editorialists perceived as flaws in the study’s design, such as an inadequate loading dose of clopidogrel delivered to a quarter of the patients randomized to that arm, inadequate time allowed for the clopidogrel to fully kick in before PCI began in a third of patients, and the use of clopidogrel as the comparator drug and not a more potent alternative drug, either prasugrel or ticagrelor (N. Engl. J. Med. 2013;368:1356-7).
“Cangrelor was never tested against prasugrel or ticagrelor, and it was compared with inadequate clopidogrel treatment. That was a problem,” reiterated Dr. Richard A. Lange, one of the 2013 editorialists, when interviewed following news of cangrelor’s FDA approval. CHAMPION PHOENIX “wasn’t really a comparison [of two drugs], it was a study of an intravenous strategy, and it’s not a strategy that is needed very often,” said Dr. Lange, an interventional cardiologist and president of the Texas Tech University Health Sciences Center in El Paso. In Dr. Lange’s opinion, the only real need for an intravenous ADP-receptor antagonist is for CAD patients undergoing PCI who are unable to take an oral agent, for example because they are on a ventilator, unable to hold down an oral pill, or unconscious, which collectively are “rare” situations, he said.
Dr. Bhatt noted that another clear indication for an intravenous agent is when MI patients receive morphine for their pain, a situation recently documented to interfere with absorption of oral ADP-receptor antagonists.
From Dr. Bhatt’s perspective, the major issue is practice patterns: “Do the interventionalists treat [with an ADP-receptor antagonist] upstream or not. If they do, then they should do the math,” and determine if the expense of holding a significant minority of patients in the hospital just to allow them to clear the ADP-receptor antagonist prior to coronary bypass surgery outweighs the cost for delaying this treatment and administering cangrelor later only to patients scheduled for PCI. At the center where he practices, Brigham and Women’s Hospital in Boston, he sees a roughly equal mix of interventionalists who prefer to treat patients with clopidogrel upfront, those who treat with ticagrelor upfront, and those who practice as he does and wait until the PCI is a go.
“For my personal practice, cangrelor will fit in quite nicely,” Dr. Bhatt said.
On Twitter@mitchelzoler
Cangrelor became the first intravenous antiplatelet agent acting on ADP receptors for adult patients undergoing percutaneous coronary intervention to receive marketing approval from the Food and Drug Administration, The Medicines Company announced on June 22.
While cangrelor’s unique delivery route and rapid onset and off-set of action set it apart and may give it certain clinical advantages over the three approved oral drugs that target the same platelet receptor – clopidogrel, prasugrel (Effient), and ticagrelor (Brilinta) – cangrelor will also be distinguished by its much higher price. The standard dosage to treat one patient undergoing percutaneous coronary intervention (PCI) with cangrelor (Kengreal) will have a wholesale acquisition cost of $749, Raymond Russo, senior vice president of The Medicines Company, said at a June 23 press briefing. That prices cangrelor substantially above its brand-name competition, which costs roughly $10 for similar treatment, as well as generic clopidogrel, which costs about $3 for the same indication.
“I believe in the strength of the data that showed that cangrelor was superior to the comparator drug [clopidogrel], and if cost were not an issue I’d use cangrelor routinely, but I am not naive; cost is an issue,” said Dr. Deepak L. Bhatt, professor of medicine at Harvard University and executive director of interventional cardiology programs at Brigham and Women’s Hospital in Boston, and co–lead investigator for the CHAMPION PHOENIX pivotal trial that led to cangrelor’s approval (N. Engl. J. Med. 2013;368:1303-13).
Whether or not interventional cardiologists and the centers where they work decide to use cangrelor or one of the oral antiplatelet drugs for coronary artery disease (CAD) patients undergoing PCI will likely depend on a series of considerations that will need to take into account not just drug cost but also practice strategies, a patient’s clinical state, and the potential for ancillary costs from following an entirely different management approach.
The first issue is whether the interventionalist decides to pretreat a patient scheduled for angioplasty and possible immediate PCI following angiography with an ADP-receptor antagonist (also known as a P2Y12-receptor inhibitor) prior to the start of angiography or opts to defer that treatment until the angiography results are available and a decision is made to proceed with PCI. Recent nationwide registry data suggest that roughly half of U.S. interventionalists treat their patients upfront with an ADP-receptor antagonist, usually clopidogrel for patients with stable angina or prasugrel or ticagrelor if they have either a non-ST-elevation MI or a ST-elevation MI, while the other 50% of interventionalists will wait to administer the ADP-receptor antagonist until angiography is complete, Dr. Bhatt explained in an interview.
The advantage to upfront treatment is that by the time the patient is ready for PCI an oral ADP-receptor antagonist is fully absorbed and on board. The disadvantage is that if the coronary anatomy demands a surgical approach to revascularization many surgeons would elect not to operate on a patient freshly dosed with an antiplatelet agent, and these patients often remain hospitalized for several days until the ADP-receptor antagonist clears and the patient’s platelet function returns to normal. Angiography generally identifies 10%-15% of these patients with a CAD distribution that necessitates surgical coronary bypass, and the potential hospitalization expense of waiting for their ADP-receptor antagonist to clear could be a major cost to counterbalance the price of cangrelor, which would obviate this expense if the quick-to-start-and-to-clear cangrelor were used instead of a more lumbering oral drug, he noted.
The other 50% of U.S. interventionalists, Dr. Bhatt included, take a different approach. Recognizing the potential downside of upfront oral antiplatelet therapy if the patient is pegged for bypass surgery following angiography, they elect to wait until the angiography results are in hand. If the angiography results show the patient is destined for surgery or for medical management, then the patient receives no ADP-receptor antagonist. The cardiologist administers an ADP-receptor antagonist only if the patient’s CAD is appropriate for PCI, the fate for most of these CAD patients following angiography. It’s under these circumstances that the advantages of cangrelor kick in, as shown in the results from CHAMPION PHOENIX.
This trial randomized patients to two different types of ADP-receptor antagonist treatment while they were in the coronary catheterization laboratory. The study results showed a statistically significant, 22% relative-risk reduction in the primary endpoint in favor of intravenous cangrelor compared with oral clopidogrel delivered while patients were “on the table” in the interval between angiography and PCI. That 22% relative improvement in outcomes, driven primarily by reductions in periprocedural MIs and stent thrombosis, improved to a 31% relative-risk reduction when The Medicines Company performed a new analysis of the study results at the FDA’s request using a more stringent and conventional definition of periprocedural MIs and stent thrombosis. The time needed to perform this and other FDA-requested analyses largely caused the greater than 2-year gap between the 2013 publication of the CHAMPION PHOENIX results and the FDA’s approval.
But the editorial that accompanied the 2013 publication highlighted what the editorialists perceived as flaws in the study’s design, such as an inadequate loading dose of clopidogrel delivered to a quarter of the patients randomized to that arm, inadequate time allowed for the clopidogrel to fully kick in before PCI began in a third of patients, and the use of clopidogrel as the comparator drug and not a more potent alternative drug, either prasugrel or ticagrelor (N. Engl. J. Med. 2013;368:1356-7).
“Cangrelor was never tested against prasugrel or ticagrelor, and it was compared with inadequate clopidogrel treatment. That was a problem,” reiterated Dr. Richard A. Lange, one of the 2013 editorialists, when interviewed following news of cangrelor’s FDA approval. CHAMPION PHOENIX “wasn’t really a comparison [of two drugs], it was a study of an intravenous strategy, and it’s not a strategy that is needed very often,” said Dr. Lange, an interventional cardiologist and president of the Texas Tech University Health Sciences Center in El Paso. In Dr. Lange’s opinion, the only real need for an intravenous ADP-receptor antagonist is for CAD patients undergoing PCI who are unable to take an oral agent, for example because they are on a ventilator, unable to hold down an oral pill, or unconscious, which collectively are “rare” situations, he said.
Dr. Bhatt noted that another clear indication for an intravenous agent is when MI patients receive morphine for their pain, a situation recently documented to interfere with absorption of oral ADP-receptor antagonists.
From Dr. Bhatt’s perspective, the major issue is practice patterns: “Do the interventionalists treat [with an ADP-receptor antagonist] upstream or not. If they do, then they should do the math,” and determine if the expense of holding a significant minority of patients in the hospital just to allow them to clear the ADP-receptor antagonist prior to coronary bypass surgery outweighs the cost for delaying this treatment and administering cangrelor later only to patients scheduled for PCI. At the center where he practices, Brigham and Women’s Hospital in Boston, he sees a roughly equal mix of interventionalists who prefer to treat patients with clopidogrel upfront, those who treat with ticagrelor upfront, and those who practice as he does and wait until the PCI is a go.
“For my personal practice, cangrelor will fit in quite nicely,” Dr. Bhatt said.
On Twitter@mitchelzoler
Cangrelor became the first intravenous antiplatelet agent acting on ADP receptors for adult patients undergoing percutaneous coronary intervention to receive marketing approval from the Food and Drug Administration, The Medicines Company announced on June 22.
While cangrelor’s unique delivery route and rapid onset and off-set of action set it apart and may give it certain clinical advantages over the three approved oral drugs that target the same platelet receptor – clopidogrel, prasugrel (Effient), and ticagrelor (Brilinta) – cangrelor will also be distinguished by its much higher price. The standard dosage to treat one patient undergoing percutaneous coronary intervention (PCI) with cangrelor (Kengreal) will have a wholesale acquisition cost of $749, Raymond Russo, senior vice president of The Medicines Company, said at a June 23 press briefing. That prices cangrelor substantially above its brand-name competition, which costs roughly $10 for similar treatment, as well as generic clopidogrel, which costs about $3 for the same indication.
“I believe in the strength of the data that showed that cangrelor was superior to the comparator drug [clopidogrel], and if cost were not an issue I’d use cangrelor routinely, but I am not naive; cost is an issue,” said Dr. Deepak L. Bhatt, professor of medicine at Harvard University and executive director of interventional cardiology programs at Brigham and Women’s Hospital in Boston, and co–lead investigator for the CHAMPION PHOENIX pivotal trial that led to cangrelor’s approval (N. Engl. J. Med. 2013;368:1303-13).
Whether or not interventional cardiologists and the centers where they work decide to use cangrelor or one of the oral antiplatelet drugs for coronary artery disease (CAD) patients undergoing PCI will likely depend on a series of considerations that will need to take into account not just drug cost but also practice strategies, a patient’s clinical state, and the potential for ancillary costs from following an entirely different management approach.
The first issue is whether the interventionalist decides to pretreat a patient scheduled for angioplasty and possible immediate PCI following angiography with an ADP-receptor antagonist (also known as a P2Y12-receptor inhibitor) prior to the start of angiography or opts to defer that treatment until the angiography results are available and a decision is made to proceed with PCI. Recent nationwide registry data suggest that roughly half of U.S. interventionalists treat their patients upfront with an ADP-receptor antagonist, usually clopidogrel for patients with stable angina or prasugrel or ticagrelor if they have either a non-ST-elevation MI or a ST-elevation MI, while the other 50% of interventionalists will wait to administer the ADP-receptor antagonist until angiography is complete, Dr. Bhatt explained in an interview.
The advantage to upfront treatment is that by the time the patient is ready for PCI an oral ADP-receptor antagonist is fully absorbed and on board. The disadvantage is that if the coronary anatomy demands a surgical approach to revascularization many surgeons would elect not to operate on a patient freshly dosed with an antiplatelet agent, and these patients often remain hospitalized for several days until the ADP-receptor antagonist clears and the patient’s platelet function returns to normal. Angiography generally identifies 10%-15% of these patients with a CAD distribution that necessitates surgical coronary bypass, and the potential hospitalization expense of waiting for their ADP-receptor antagonist to clear could be a major cost to counterbalance the price of cangrelor, which would obviate this expense if the quick-to-start-and-to-clear cangrelor were used instead of a more lumbering oral drug, he noted.
The other 50% of U.S. interventionalists, Dr. Bhatt included, take a different approach. Recognizing the potential downside of upfront oral antiplatelet therapy if the patient is pegged for bypass surgery following angiography, they elect to wait until the angiography results are in hand. If the angiography results show the patient is destined for surgery or for medical management, then the patient receives no ADP-receptor antagonist. The cardiologist administers an ADP-receptor antagonist only if the patient’s CAD is appropriate for PCI, the fate for most of these CAD patients following angiography. It’s under these circumstances that the advantages of cangrelor kick in, as shown in the results from CHAMPION PHOENIX.
This trial randomized patients to two different types of ADP-receptor antagonist treatment while they were in the coronary catheterization laboratory. The study results showed a statistically significant, 22% relative-risk reduction in the primary endpoint in favor of intravenous cangrelor compared with oral clopidogrel delivered while patients were “on the table” in the interval between angiography and PCI. That 22% relative improvement in outcomes, driven primarily by reductions in periprocedural MIs and stent thrombosis, improved to a 31% relative-risk reduction when The Medicines Company performed a new analysis of the study results at the FDA’s request using a more stringent and conventional definition of periprocedural MIs and stent thrombosis. The time needed to perform this and other FDA-requested analyses largely caused the greater than 2-year gap between the 2013 publication of the CHAMPION PHOENIX results and the FDA’s approval.
But the editorial that accompanied the 2013 publication highlighted what the editorialists perceived as flaws in the study’s design, such as an inadequate loading dose of clopidogrel delivered to a quarter of the patients randomized to that arm, inadequate time allowed for the clopidogrel to fully kick in before PCI began in a third of patients, and the use of clopidogrel as the comparator drug and not a more potent alternative drug, either prasugrel or ticagrelor (N. Engl. J. Med. 2013;368:1356-7).
“Cangrelor was never tested against prasugrel or ticagrelor, and it was compared with inadequate clopidogrel treatment. That was a problem,” reiterated Dr. Richard A. Lange, one of the 2013 editorialists, when interviewed following news of cangrelor’s FDA approval. CHAMPION PHOENIX “wasn’t really a comparison [of two drugs], it was a study of an intravenous strategy, and it’s not a strategy that is needed very often,” said Dr. Lange, an interventional cardiologist and president of the Texas Tech University Health Sciences Center in El Paso. In Dr. Lange’s opinion, the only real need for an intravenous ADP-receptor antagonist is for CAD patients undergoing PCI who are unable to take an oral agent, for example because they are on a ventilator, unable to hold down an oral pill, or unconscious, which collectively are “rare” situations, he said.
Dr. Bhatt noted that another clear indication for an intravenous agent is when MI patients receive morphine for their pain, a situation recently documented to interfere with absorption of oral ADP-receptor antagonists.
From Dr. Bhatt’s perspective, the major issue is practice patterns: “Do the interventionalists treat [with an ADP-receptor antagonist] upstream or not. If they do, then they should do the math,” and determine if the expense of holding a significant minority of patients in the hospital just to allow them to clear the ADP-receptor antagonist prior to coronary bypass surgery outweighs the cost for delaying this treatment and administering cangrelor later only to patients scheduled for PCI. At the center where he practices, Brigham and Women’s Hospital in Boston, he sees a roughly equal mix of interventionalists who prefer to treat patients with clopidogrel upfront, those who treat with ticagrelor upfront, and those who practice as he does and wait until the PCI is a go.
“For my personal practice, cangrelor will fit in quite nicely,” Dr. Bhatt said.
On Twitter@mitchelzoler
EULAR: Biologic tapering in RA shows cost efficacy
ROME – Patients with rheumatoid arthritis in sustained remission on a biologic drug successfully remained in remission most of the time while gradually stepping down to a longer dosage interval or eventually going off the biologic entirely in a controlled, multicenter French trial with 98 patients followed for 18 months.
The results also showed that while patients who were maintained throughout 18 months on full biologic-drug dosage fared slightly better clinically, the taper-down strategy saved an average 53,417 euro (about $60,000 US) for each quality-adjusted life-year (QALY) decrement caused by the step-down treatment, Dr. Antoine Vanier reported at the European Congress of Rheumatology. The actual decrement in QALYs among the 44 patients randomized to the step-down arm during the 18 month study averaged 0.158 QALYs, compared with the 54 patients maintained on full dose. The actual cost savings over 18 months averaged 8,440 euro (about $9,500 US) per patient, said Dr. Vanier, a rheumatologist and biostatistician at Pierre and Marie Curie University in Paris.
In addition, a numerically larger percentage of patients in the step-down arm, 61%, rated their health status “acceptable,” compared with 44% among those in the maintenance arm, although this difference was not statistically significant.
The Spacing of TNF-blocker Injections in Rheumatoid Arthritis Study (STRASS) enrolled adult rheumatoid arthritis patients on subcutaneous treatment with either 40 mg adalimumab (Humira) every 14 days or 50 mg etanercept (Enbrel) every 7 days for at least a year and who maintained a 28-joint disease activity score (DAS28) of 2.6 or below for at least 6 months and had no radiographic joint progression for at least a year. Patients could be on either monotherapy with one of these biologic drugs or on a stable regimen that also included either methotrexate or leflunomide, and patients could also receive up to 5 mg/day prednisone.
The researchers randomized patients to either maintain their entry regimen or start on a program that serially increased the time between biologic injections every 3 months. The adalimumab dosing interval increased to a 40-mg injection every 21 days, 28 days, 42 days, and then patients who remained in remission with an injection every 42 days for 3 months stopped adalimumab treatment entirely. Among the etanercept patients, the between-dose intervals increased to 10 days, 14 days, 21 days, and then a complete stop. Patients who experienced a flare, with their DAS28 rising above 2.6, returned to a more frequent dosing interval able to lower their DAS28 to 2.6 or less once again and regain remission.
After 18 months, 8 (18%) patients in the step-down arm remained on their entry-dosage interval, 19 (43%) patients maintained remission on a lengthened-dosing interval, 15 (34%) patients completely stopped their biologic, and 2 (5%) patients had left the study. In the maintenance arm, all 54 patients remained in the study and in remission on their entry-dosage schedule.
A majority of the patients in the step-down arm remained on their reduced- or no-dose regimen after the trial completed, noted Dr. Bruno Fautrel, senior investigator of STRASS and professor of rheumatology at Pierre and Marie Curie University, Paris. The researchers have so far not been able to identify any patient-specific features to prospectively identify the patients most likely to successfully undergo biologic step-down, Dr. Fautrel added.
Despite this uncertainty as to which patients are best suited to a step-down strategy, the possibility of successfully stepping-down biologic treatment for most RA patients to save on drug costs without compromising patient outcomes makes it “worth considering” on a case-by-case basis, Dr. Vanier said.
On Twitter @mitchelzoler
Increasingly, the treatment model for rheumatoid arthritis patients in stable remission on treatment with a biologic drug includes considering an increase of the interval between doses. At the center where I work we already do this for a majority of our RA patients. Most patients are not able to completely stop their biologic, but they often can extend the dosing interval without flaring.
In my experience, many RA patients are savvy enough to gradually find their own biologic sweet spot, the between-dose time interval that leaves them feeling good and keep them in remission, while also cutting down on their drug expense. Roughly half the RA patients in my practice who are on a biologic drug take it at a prolonged interval, compared with the label’s dosage.
I’m not surprised that quality-adjusted life years were slightly reduced in this study among the patients randomized to the step-down arm because it is hard for each patient in a tightly structured trial to find their dosing-interval sweet spot, compared with patients in a routine-practice setting. The step-down strategy approach mandated in this study eliminated the flexibility that is possible in the real world because it applies a one-size-fits-all approach. It is much easier for patients and clinicians to find the optimal dosing interval for each individual patient when tweaking of the interval can be tailored individually.
Dr. James R. O’Dell is professor and chief of rheumatology at the University of Nebraska Medical Center in Omaha. He has been an advisor to Medac, Antares, AbbVie, Lilly, and Bristol-Myers Squibb. He made these comments in an interview.
Increasingly, the treatment model for rheumatoid arthritis patients in stable remission on treatment with a biologic drug includes considering an increase of the interval between doses. At the center where I work we already do this for a majority of our RA patients. Most patients are not able to completely stop their biologic, but they often can extend the dosing interval without flaring.
In my experience, many RA patients are savvy enough to gradually find their own biologic sweet spot, the between-dose time interval that leaves them feeling good and keep them in remission, while also cutting down on their drug expense. Roughly half the RA patients in my practice who are on a biologic drug take it at a prolonged interval, compared with the label’s dosage.
I’m not surprised that quality-adjusted life years were slightly reduced in this study among the patients randomized to the step-down arm because it is hard for each patient in a tightly structured trial to find their dosing-interval sweet spot, compared with patients in a routine-practice setting. The step-down strategy approach mandated in this study eliminated the flexibility that is possible in the real world because it applies a one-size-fits-all approach. It is much easier for patients and clinicians to find the optimal dosing interval for each individual patient when tweaking of the interval can be tailored individually.
Dr. James R. O’Dell is professor and chief of rheumatology at the University of Nebraska Medical Center in Omaha. He has been an advisor to Medac, Antares, AbbVie, Lilly, and Bristol-Myers Squibb. He made these comments in an interview.
Increasingly, the treatment model for rheumatoid arthritis patients in stable remission on treatment with a biologic drug includes considering an increase of the interval between doses. At the center where I work we already do this for a majority of our RA patients. Most patients are not able to completely stop their biologic, but they often can extend the dosing interval without flaring.
In my experience, many RA patients are savvy enough to gradually find their own biologic sweet spot, the between-dose time interval that leaves them feeling good and keep them in remission, while also cutting down on their drug expense. Roughly half the RA patients in my practice who are on a biologic drug take it at a prolonged interval, compared with the label’s dosage.
I’m not surprised that quality-adjusted life years were slightly reduced in this study among the patients randomized to the step-down arm because it is hard for each patient in a tightly structured trial to find their dosing-interval sweet spot, compared with patients in a routine-practice setting. The step-down strategy approach mandated in this study eliminated the flexibility that is possible in the real world because it applies a one-size-fits-all approach. It is much easier for patients and clinicians to find the optimal dosing interval for each individual patient when tweaking of the interval can be tailored individually.
Dr. James R. O’Dell is professor and chief of rheumatology at the University of Nebraska Medical Center in Omaha. He has been an advisor to Medac, Antares, AbbVie, Lilly, and Bristol-Myers Squibb. He made these comments in an interview.
ROME – Patients with rheumatoid arthritis in sustained remission on a biologic drug successfully remained in remission most of the time while gradually stepping down to a longer dosage interval or eventually going off the biologic entirely in a controlled, multicenter French trial with 98 patients followed for 18 months.
The results also showed that while patients who were maintained throughout 18 months on full biologic-drug dosage fared slightly better clinically, the taper-down strategy saved an average 53,417 euro (about $60,000 US) for each quality-adjusted life-year (QALY) decrement caused by the step-down treatment, Dr. Antoine Vanier reported at the European Congress of Rheumatology. The actual decrement in QALYs among the 44 patients randomized to the step-down arm during the 18 month study averaged 0.158 QALYs, compared with the 54 patients maintained on full dose. The actual cost savings over 18 months averaged 8,440 euro (about $9,500 US) per patient, said Dr. Vanier, a rheumatologist and biostatistician at Pierre and Marie Curie University in Paris.
In addition, a numerically larger percentage of patients in the step-down arm, 61%, rated their health status “acceptable,” compared with 44% among those in the maintenance arm, although this difference was not statistically significant.
The Spacing of TNF-blocker Injections in Rheumatoid Arthritis Study (STRASS) enrolled adult rheumatoid arthritis patients on subcutaneous treatment with either 40 mg adalimumab (Humira) every 14 days or 50 mg etanercept (Enbrel) every 7 days for at least a year and who maintained a 28-joint disease activity score (DAS28) of 2.6 or below for at least 6 months and had no radiographic joint progression for at least a year. Patients could be on either monotherapy with one of these biologic drugs or on a stable regimen that also included either methotrexate or leflunomide, and patients could also receive up to 5 mg/day prednisone.
The researchers randomized patients to either maintain their entry regimen or start on a program that serially increased the time between biologic injections every 3 months. The adalimumab dosing interval increased to a 40-mg injection every 21 days, 28 days, 42 days, and then patients who remained in remission with an injection every 42 days for 3 months stopped adalimumab treatment entirely. Among the etanercept patients, the between-dose intervals increased to 10 days, 14 days, 21 days, and then a complete stop. Patients who experienced a flare, with their DAS28 rising above 2.6, returned to a more frequent dosing interval able to lower their DAS28 to 2.6 or less once again and regain remission.
After 18 months, 8 (18%) patients in the step-down arm remained on their entry-dosage interval, 19 (43%) patients maintained remission on a lengthened-dosing interval, 15 (34%) patients completely stopped their biologic, and 2 (5%) patients had left the study. In the maintenance arm, all 54 patients remained in the study and in remission on their entry-dosage schedule.
A majority of the patients in the step-down arm remained on their reduced- or no-dose regimen after the trial completed, noted Dr. Bruno Fautrel, senior investigator of STRASS and professor of rheumatology at Pierre and Marie Curie University, Paris. The researchers have so far not been able to identify any patient-specific features to prospectively identify the patients most likely to successfully undergo biologic step-down, Dr. Fautrel added.
Despite this uncertainty as to which patients are best suited to a step-down strategy, the possibility of successfully stepping-down biologic treatment for most RA patients to save on drug costs without compromising patient outcomes makes it “worth considering” on a case-by-case basis, Dr. Vanier said.
On Twitter @mitchelzoler
ROME – Patients with rheumatoid arthritis in sustained remission on a biologic drug successfully remained in remission most of the time while gradually stepping down to a longer dosage interval or eventually going off the biologic entirely in a controlled, multicenter French trial with 98 patients followed for 18 months.
The results also showed that while patients who were maintained throughout 18 months on full biologic-drug dosage fared slightly better clinically, the taper-down strategy saved an average 53,417 euro (about $60,000 US) for each quality-adjusted life-year (QALY) decrement caused by the step-down treatment, Dr. Antoine Vanier reported at the European Congress of Rheumatology. The actual decrement in QALYs among the 44 patients randomized to the step-down arm during the 18 month study averaged 0.158 QALYs, compared with the 54 patients maintained on full dose. The actual cost savings over 18 months averaged 8,440 euro (about $9,500 US) per patient, said Dr. Vanier, a rheumatologist and biostatistician at Pierre and Marie Curie University in Paris.
In addition, a numerically larger percentage of patients in the step-down arm, 61%, rated their health status “acceptable,” compared with 44% among those in the maintenance arm, although this difference was not statistically significant.
The Spacing of TNF-blocker Injections in Rheumatoid Arthritis Study (STRASS) enrolled adult rheumatoid arthritis patients on subcutaneous treatment with either 40 mg adalimumab (Humira) every 14 days or 50 mg etanercept (Enbrel) every 7 days for at least a year and who maintained a 28-joint disease activity score (DAS28) of 2.6 or below for at least 6 months and had no radiographic joint progression for at least a year. Patients could be on either monotherapy with one of these biologic drugs or on a stable regimen that also included either methotrexate or leflunomide, and patients could also receive up to 5 mg/day prednisone.
The researchers randomized patients to either maintain their entry regimen or start on a program that serially increased the time between biologic injections every 3 months. The adalimumab dosing interval increased to a 40-mg injection every 21 days, 28 days, 42 days, and then patients who remained in remission with an injection every 42 days for 3 months stopped adalimumab treatment entirely. Among the etanercept patients, the between-dose intervals increased to 10 days, 14 days, 21 days, and then a complete stop. Patients who experienced a flare, with their DAS28 rising above 2.6, returned to a more frequent dosing interval able to lower their DAS28 to 2.6 or less once again and regain remission.
After 18 months, 8 (18%) patients in the step-down arm remained on their entry-dosage interval, 19 (43%) patients maintained remission on a lengthened-dosing interval, 15 (34%) patients completely stopped their biologic, and 2 (5%) patients had left the study. In the maintenance arm, all 54 patients remained in the study and in remission on their entry-dosage schedule.
A majority of the patients in the step-down arm remained on their reduced- or no-dose regimen after the trial completed, noted Dr. Bruno Fautrel, senior investigator of STRASS and professor of rheumatology at Pierre and Marie Curie University, Paris. The researchers have so far not been able to identify any patient-specific features to prospectively identify the patients most likely to successfully undergo biologic step-down, Dr. Fautrel added.
Despite this uncertainty as to which patients are best suited to a step-down strategy, the possibility of successfully stepping-down biologic treatment for most RA patients to save on drug costs without compromising patient outcomes makes it “worth considering” on a case-by-case basis, Dr. Vanier said.
On Twitter @mitchelzoler
AT THE EULAR 2015 CONGRESS
Key clinical point: Most rheumatoid arthritis patients successfully increased the interval between injections of a biologic drug resulting in cost savings without clinical consequence.
Major finding: Stepped-down biologic dosages maintained remission in 43% of patients, and 34% of patients completely stopped biologic treatment.
Data source: STRASS, a multicenter, controlled French study with 98 rheumatoid arthritis patients.
Disclosures: Dr. Vanier had no disclosures. Dr. Fautrel has been a consultant to nine drug companies.
EULAR: Panel previews updated CVD recommendations
ROME – The interval for assessing cardiovascular disease risk in patients with at least one inflamed joint can be as long as 5 years, depending on the patient, according to revised recommendations issued by a European League Against Rheumatism expert panel. The first edition of the recommendations called for annual assessment.
“We leave the assessment interval up to each clinician. Annually is very hard to incorporate into clinical practice,” said Dr. Michael T. Nurmohamed, convenor of both the initial recommendation panel as well as the group that produced the new revision. He previewed the updated recommendations during a talk at the European Congress of Rheumatology. The final form of the revised recommendations, which apply to patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, will soon be posted online and published, he said.
The context for cardiovascular disease risk assessment of patients with these rheumatoid diseases who are in primary-prevention mode has changed since the initial version was released in 2009 (Ann. Rheum. Dis. 2010;69:325-31). That changed context led to a rethinking of the appropriate interval for risk-factor assessment, said Dr. Nurmohamed, professor and head of rheumatology research at VU University Medical Center in Amsterdam. “In 2009, tight control of rheumatoid diseases generally did not exist,” he said in an interview.
In patients with well-controlled rheumatoid disease, “you can assess their cardiovascular disease [CVD] risk, and if the risk is very low” you can defer the next follow-up assessment for 5 years or longer. But if a patient’s CVD risk is high, assess the patient more often, Dr. Nurmohamed suggested. The recommendations also call for an updated CVD risk assessment following a “major change” in antirheumatoid therapy.
The updated recommendations include two other notable changes. First, there is now a much deeper evidence base behind the need for CVD risk assessment and management in patients with psoriatic arthritis or ankylosing spondylitis. “We mentioned them before, but the data weren’t all that hard. We now have more evidence,” he said in an interview.
Second, the revised recommendations say that ultrasound examination of atherosclerotic plaque number and volume in a patient’s carotid artery “may be considered.” Dr. Nurmohamed acknowledged that carotid examination by ultrasound is very discretionary; it can provide useful risk information, but “not every rheumatologist will do it.”
Most other aspects of the revised recommendations remain similar to the 2009 edition. They emphasize controlling inflammation to lower CVD risk, multiplying a patient’s CVD risk score by a factor of 1.5 to better estimate their increased risk level due to their rheumatic disease, cautious use of nonsteroidal anti-inflammatory drugs, and minimized use of glucocorticoids. Multiplying a patient’s CVD risk score results in a “rough” risk estimate, he cautioned. “The problem is we use 1.5 for all patients, regardless of their rheumatoid-disease duration,” he said.
Recommended interventions to reduce a patient’s CVD risk include lifestyle steps of healthy diet, regular exercise, and smoking cessation, and the standard drug interventions for reducing CVD risk: antihypertensive medications and lipid-lowering drugs, especially statins. Target levels for treating hypertension and hyperlipidemia remain the same as for primary prevention in the general population, he said. CVD risk assessment and management steps for patients with one of the covered rheumatoid diseases and established CVD are the same as for standard secondary-prevention measures in the general population.
A notable gap in the revision is the continued absence of recommendations for patients with gout. “Gout is on our research agenda, but represents an enormous task,” Dr. Nurmohamed said. He anticipates that his panel will eventually develop recommendations for managing CVD risk in gout patients.
On Twitter @mitchelzoler
ROME – The interval for assessing cardiovascular disease risk in patients with at least one inflamed joint can be as long as 5 years, depending on the patient, according to revised recommendations issued by a European League Against Rheumatism expert panel. The first edition of the recommendations called for annual assessment.
“We leave the assessment interval up to each clinician. Annually is very hard to incorporate into clinical practice,” said Dr. Michael T. Nurmohamed, convenor of both the initial recommendation panel as well as the group that produced the new revision. He previewed the updated recommendations during a talk at the European Congress of Rheumatology. The final form of the revised recommendations, which apply to patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, will soon be posted online and published, he said.
The context for cardiovascular disease risk assessment of patients with these rheumatoid diseases who are in primary-prevention mode has changed since the initial version was released in 2009 (Ann. Rheum. Dis. 2010;69:325-31). That changed context led to a rethinking of the appropriate interval for risk-factor assessment, said Dr. Nurmohamed, professor and head of rheumatology research at VU University Medical Center in Amsterdam. “In 2009, tight control of rheumatoid diseases generally did not exist,” he said in an interview.
In patients with well-controlled rheumatoid disease, “you can assess their cardiovascular disease [CVD] risk, and if the risk is very low” you can defer the next follow-up assessment for 5 years or longer. But if a patient’s CVD risk is high, assess the patient more often, Dr. Nurmohamed suggested. The recommendations also call for an updated CVD risk assessment following a “major change” in antirheumatoid therapy.
The updated recommendations include two other notable changes. First, there is now a much deeper evidence base behind the need for CVD risk assessment and management in patients with psoriatic arthritis or ankylosing spondylitis. “We mentioned them before, but the data weren’t all that hard. We now have more evidence,” he said in an interview.
Second, the revised recommendations say that ultrasound examination of atherosclerotic plaque number and volume in a patient’s carotid artery “may be considered.” Dr. Nurmohamed acknowledged that carotid examination by ultrasound is very discretionary; it can provide useful risk information, but “not every rheumatologist will do it.”
Most other aspects of the revised recommendations remain similar to the 2009 edition. They emphasize controlling inflammation to lower CVD risk, multiplying a patient’s CVD risk score by a factor of 1.5 to better estimate their increased risk level due to their rheumatic disease, cautious use of nonsteroidal anti-inflammatory drugs, and minimized use of glucocorticoids. Multiplying a patient’s CVD risk score results in a “rough” risk estimate, he cautioned. “The problem is we use 1.5 for all patients, regardless of their rheumatoid-disease duration,” he said.
Recommended interventions to reduce a patient’s CVD risk include lifestyle steps of healthy diet, regular exercise, and smoking cessation, and the standard drug interventions for reducing CVD risk: antihypertensive medications and lipid-lowering drugs, especially statins. Target levels for treating hypertension and hyperlipidemia remain the same as for primary prevention in the general population, he said. CVD risk assessment and management steps for patients with one of the covered rheumatoid diseases and established CVD are the same as for standard secondary-prevention measures in the general population.
A notable gap in the revision is the continued absence of recommendations for patients with gout. “Gout is on our research agenda, but represents an enormous task,” Dr. Nurmohamed said. He anticipates that his panel will eventually develop recommendations for managing CVD risk in gout patients.
On Twitter @mitchelzoler
ROME – The interval for assessing cardiovascular disease risk in patients with at least one inflamed joint can be as long as 5 years, depending on the patient, according to revised recommendations issued by a European League Against Rheumatism expert panel. The first edition of the recommendations called for annual assessment.
“We leave the assessment interval up to each clinician. Annually is very hard to incorporate into clinical practice,” said Dr. Michael T. Nurmohamed, convenor of both the initial recommendation panel as well as the group that produced the new revision. He previewed the updated recommendations during a talk at the European Congress of Rheumatology. The final form of the revised recommendations, which apply to patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, will soon be posted online and published, he said.
The context for cardiovascular disease risk assessment of patients with these rheumatoid diseases who are in primary-prevention mode has changed since the initial version was released in 2009 (Ann. Rheum. Dis. 2010;69:325-31). That changed context led to a rethinking of the appropriate interval for risk-factor assessment, said Dr. Nurmohamed, professor and head of rheumatology research at VU University Medical Center in Amsterdam. “In 2009, tight control of rheumatoid diseases generally did not exist,” he said in an interview.
In patients with well-controlled rheumatoid disease, “you can assess their cardiovascular disease [CVD] risk, and if the risk is very low” you can defer the next follow-up assessment for 5 years or longer. But if a patient’s CVD risk is high, assess the patient more often, Dr. Nurmohamed suggested. The recommendations also call for an updated CVD risk assessment following a “major change” in antirheumatoid therapy.
The updated recommendations include two other notable changes. First, there is now a much deeper evidence base behind the need for CVD risk assessment and management in patients with psoriatic arthritis or ankylosing spondylitis. “We mentioned them before, but the data weren’t all that hard. We now have more evidence,” he said in an interview.
Second, the revised recommendations say that ultrasound examination of atherosclerotic plaque number and volume in a patient’s carotid artery “may be considered.” Dr. Nurmohamed acknowledged that carotid examination by ultrasound is very discretionary; it can provide useful risk information, but “not every rheumatologist will do it.”
Most other aspects of the revised recommendations remain similar to the 2009 edition. They emphasize controlling inflammation to lower CVD risk, multiplying a patient’s CVD risk score by a factor of 1.5 to better estimate their increased risk level due to their rheumatic disease, cautious use of nonsteroidal anti-inflammatory drugs, and minimized use of glucocorticoids. Multiplying a patient’s CVD risk score results in a “rough” risk estimate, he cautioned. “The problem is we use 1.5 for all patients, regardless of their rheumatoid-disease duration,” he said.
Recommended interventions to reduce a patient’s CVD risk include lifestyle steps of healthy diet, regular exercise, and smoking cessation, and the standard drug interventions for reducing CVD risk: antihypertensive medications and lipid-lowering drugs, especially statins. Target levels for treating hypertension and hyperlipidemia remain the same as for primary prevention in the general population, he said. CVD risk assessment and management steps for patients with one of the covered rheumatoid diseases and established CVD are the same as for standard secondary-prevention measures in the general population.
A notable gap in the revision is the continued absence of recommendations for patients with gout. “Gout is on our research agenda, but represents an enormous task,” Dr. Nurmohamed said. He anticipates that his panel will eventually develop recommendations for managing CVD risk in gout patients.
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE EULAR 2015 Congress
EULAR: Women with RA have increased cervical neoplasia rates
ROME – Women with rheumatoid arthritis who have never been treated with a biologic drug had a modest but statistically significant increased rate of cervical intraepithelial neoplasia in a case-control study with more than 335,000 women.
The analysis showed an adjusted excess hazard for developing cervical intraepithelial neoplasia (CIN) I of 53%, compared with the general population, and an excess 39% rate of CIN II or III, both statistically significant differences, Dr. Hjalmar Wadstrom reported in a poster at the European Congress of Rheumatology.
The analysis also showed a small increase in the relative rate of invasive cervical cancers among the women with rheumatoid arthritis (RA) on treatment with conventional disease-modifying drugs, such as methotrexate, who never received a biologic disease-modifying drug. The 9% relative increase in the rate of invasive cancer, compared with the general population, did not achieve statistical significance, reported Dr. Wadstrom, a clinical epidemiology researcher at the Karolinska Institute in Stockholm.
The “moderately but not dramatically” increased rate of CIN “is not a reason for big concern or alarm,” but highlights that women with RA should comply with local cervical cancer–screening recommendations and programs, said Dr. Johan Askling, professor of rheumatology and clinical epidemiology at Karolinska and senior author of the study.
“It would be a shame if these RA patients with a small increased risk did not attend the [cervical screening] programs we have set up. Clinicians should make sure that women with RA attend to screening because nonattendance is their major risk factor,” he said in an interview. “Our findings don’t call for a change in screening recommendations, they just highlight the importance of attending to screening” in women with RA, Dr. Askling said.
The researchers ran a linkage analysis of Swedish registries and identified 34,984 adult women with RA and matched them with 300,331 women drawn from the general Swedish population. Age of the RA patients ranged from 18 to 97 years with a median age of 62 years, and they selected general-population controls who matched this group. In the regression analyses they ran to calculate hazard ratios they adjusted for age, education, prior cervical screening, comorbidities, marital status, and time hospitalized during prior 5 years. The analysis included CIN and invasive cancer cases during 14 years of follow-up, 1999-2012.
Both Dr. Wadstrom and Dr. Askling cited two potential factors behind the increased rates of CIN I, II, and III in women with RA: the inflammatory state of RA and treatment with immunosuppressive nonbiologic agents, such as methotrexate.
The increased CIN rates found in this analysis were also “seen in other patients treated with potent immunosuppressive drugs,” like organ transplant patients, Dr. Askling noted.
The current study serves as prelude to an analysis he and his associates are now running to assess cervical neoplasia and cancer rates among women with RA treated with biologic disease-modifying drugs.
On Twitter @mitchelzoler
ROME – Women with rheumatoid arthritis who have never been treated with a biologic drug had a modest but statistically significant increased rate of cervical intraepithelial neoplasia in a case-control study with more than 335,000 women.
The analysis showed an adjusted excess hazard for developing cervical intraepithelial neoplasia (CIN) I of 53%, compared with the general population, and an excess 39% rate of CIN II or III, both statistically significant differences, Dr. Hjalmar Wadstrom reported in a poster at the European Congress of Rheumatology.
The analysis also showed a small increase in the relative rate of invasive cervical cancers among the women with rheumatoid arthritis (RA) on treatment with conventional disease-modifying drugs, such as methotrexate, who never received a biologic disease-modifying drug. The 9% relative increase in the rate of invasive cancer, compared with the general population, did not achieve statistical significance, reported Dr. Wadstrom, a clinical epidemiology researcher at the Karolinska Institute in Stockholm.
The “moderately but not dramatically” increased rate of CIN “is not a reason for big concern or alarm,” but highlights that women with RA should comply with local cervical cancer–screening recommendations and programs, said Dr. Johan Askling, professor of rheumatology and clinical epidemiology at Karolinska and senior author of the study.
“It would be a shame if these RA patients with a small increased risk did not attend the [cervical screening] programs we have set up. Clinicians should make sure that women with RA attend to screening because nonattendance is their major risk factor,” he said in an interview. “Our findings don’t call for a change in screening recommendations, they just highlight the importance of attending to screening” in women with RA, Dr. Askling said.
The researchers ran a linkage analysis of Swedish registries and identified 34,984 adult women with RA and matched them with 300,331 women drawn from the general Swedish population. Age of the RA patients ranged from 18 to 97 years with a median age of 62 years, and they selected general-population controls who matched this group. In the regression analyses they ran to calculate hazard ratios they adjusted for age, education, prior cervical screening, comorbidities, marital status, and time hospitalized during prior 5 years. The analysis included CIN and invasive cancer cases during 14 years of follow-up, 1999-2012.
Both Dr. Wadstrom and Dr. Askling cited two potential factors behind the increased rates of CIN I, II, and III in women with RA: the inflammatory state of RA and treatment with immunosuppressive nonbiologic agents, such as methotrexate.
The increased CIN rates found in this analysis were also “seen in other patients treated with potent immunosuppressive drugs,” like organ transplant patients, Dr. Askling noted.
The current study serves as prelude to an analysis he and his associates are now running to assess cervical neoplasia and cancer rates among women with RA treated with biologic disease-modifying drugs.
On Twitter @mitchelzoler
ROME – Women with rheumatoid arthritis who have never been treated with a biologic drug had a modest but statistically significant increased rate of cervical intraepithelial neoplasia in a case-control study with more than 335,000 women.
The analysis showed an adjusted excess hazard for developing cervical intraepithelial neoplasia (CIN) I of 53%, compared with the general population, and an excess 39% rate of CIN II or III, both statistically significant differences, Dr. Hjalmar Wadstrom reported in a poster at the European Congress of Rheumatology.
The analysis also showed a small increase in the relative rate of invasive cervical cancers among the women with rheumatoid arthritis (RA) on treatment with conventional disease-modifying drugs, such as methotrexate, who never received a biologic disease-modifying drug. The 9% relative increase in the rate of invasive cancer, compared with the general population, did not achieve statistical significance, reported Dr. Wadstrom, a clinical epidemiology researcher at the Karolinska Institute in Stockholm.
The “moderately but not dramatically” increased rate of CIN “is not a reason for big concern or alarm,” but highlights that women with RA should comply with local cervical cancer–screening recommendations and programs, said Dr. Johan Askling, professor of rheumatology and clinical epidemiology at Karolinska and senior author of the study.
“It would be a shame if these RA patients with a small increased risk did not attend the [cervical screening] programs we have set up. Clinicians should make sure that women with RA attend to screening because nonattendance is their major risk factor,” he said in an interview. “Our findings don’t call for a change in screening recommendations, they just highlight the importance of attending to screening” in women with RA, Dr. Askling said.
The researchers ran a linkage analysis of Swedish registries and identified 34,984 adult women with RA and matched them with 300,331 women drawn from the general Swedish population. Age of the RA patients ranged from 18 to 97 years with a median age of 62 years, and they selected general-population controls who matched this group. In the regression analyses they ran to calculate hazard ratios they adjusted for age, education, prior cervical screening, comorbidities, marital status, and time hospitalized during prior 5 years. The analysis included CIN and invasive cancer cases during 14 years of follow-up, 1999-2012.
Both Dr. Wadstrom and Dr. Askling cited two potential factors behind the increased rates of CIN I, II, and III in women with RA: the inflammatory state of RA and treatment with immunosuppressive nonbiologic agents, such as methotrexate.
The increased CIN rates found in this analysis were also “seen in other patients treated with potent immunosuppressive drugs,” like organ transplant patients, Dr. Askling noted.
The current study serves as prelude to an analysis he and his associates are now running to assess cervical neoplasia and cancer rates among women with RA treated with biologic disease-modifying drugs.
On Twitter @mitchelzoler
AT THE EULAR 2015 CONGRESS
Key clinical point: Women with rheumatoid arthritis had significantly increased rates of CIN I, II, and III.
Major finding: Women with RA had a 53% increased rate of CIN I and a 39% increased rate of CIN II or III.
Data source: Case-control study of women drawn from Swedish national registries with 34,984 RA patients and 300,331 women from the general population.
Disclosures: Dr. Wadstrom had no disclosures. Dr. Askling has received research support from eight drug companies.
HRS: Blacks show higher A fib–stroke risk than whites do
BOSTON – Black people with new-onset atrial fibrillation have a 60% increased risk for stroke compared with white people who have incident atrial fibrillation when not maintained on an appropriate anticlotting regimen, according to prospectively collected data from more than 56,000 subjects at a U.S. center.
But in the subgroup of new-onset atrial fibrillation (AF) patients who received appropriate treatment with aspirin or an anticoagulant, the stroke rates among white and blacks equalized. The analysis showed that 46% of the more than 3,000 people who developed AF during follow-up received aspirin if their CHA2DS2-VASc score was less than 2, or anticoagulation with warfarin or a new oral anticoagulant if their score was 2 or greater, Dr. Parin J. Patel said at the annual scientific sessions of the Heart Rhythm Society.
The majority of the followed cohort with incident atrial fibrillation did not receive this treatment, and in the total group, the relative rate of stroke among blacks exceeded that of whites by a statistically significant 60% in an analysis that adjusted for several demographic and clinical features. The excess of strokes occurred at about the same rate in black women compared with white women, and in black men compared with white men, reported Dr. Patel, an electrophysiologist at the University of Pennsylvania in Philadelphia.
The implication is that because their stroke risk is greater, blacks with AF should especially receive appropriate stroke prophylaxis and AF therapy, he said. The overall findings also highlight the substantial stroke risk faced by all AF patients.
The data came from the University of Pennsylvania Atrial Fibrillation-Free study of 91,274 people who underwent an ECG examination in the University of Pennsylvania health system during 2004-2009 along with an index clinical encounter within 30 days. Excluding patients with a prevalent AF or other arrhythmia, prevalent stroke, or incomplete data left 56,835 AF- and stroke-free people to follow for incident AF, which occurred in 3,891 patients. At the time of AF diagnosis, the average age of patients was 63 years; more than a third had hypertension; a fifth had diabetes; and a fifth had heart failure. One-third of the incident-AF group was black, 58% were white, and the remainder were from other demographic groups.
Dr. Patel and his associates defined an AF-related stroke as any that occurred within 6 months before AF diagnosis or anytime after, which occurred in 645 (17%) of the incident-AF patients. The more than 50,000 AF-free people followed in the study had a total of 3,001 strokes not related to AF during follow-up, which meant that 18% of all strokes in the entire cohort were AF related.
Among the 645 AF-related strokes, roughly half occurred during the 6 months before AF diagnosis, and the other half following AF diagnosis. An analysis that focused exclusively on strokes that occurred after AF diagnosis showed that this subset of AF-associated strokes also occurred significantly more often in blacks than in whites.
Dr. Patel had no disclosures.
On Twitter @mitchelzoler
BOSTON – Black people with new-onset atrial fibrillation have a 60% increased risk for stroke compared with white people who have incident atrial fibrillation when not maintained on an appropriate anticlotting regimen, according to prospectively collected data from more than 56,000 subjects at a U.S. center.
But in the subgroup of new-onset atrial fibrillation (AF) patients who received appropriate treatment with aspirin or an anticoagulant, the stroke rates among white and blacks equalized. The analysis showed that 46% of the more than 3,000 people who developed AF during follow-up received aspirin if their CHA2DS2-VASc score was less than 2, or anticoagulation with warfarin or a new oral anticoagulant if their score was 2 or greater, Dr. Parin J. Patel said at the annual scientific sessions of the Heart Rhythm Society.
The majority of the followed cohort with incident atrial fibrillation did not receive this treatment, and in the total group, the relative rate of stroke among blacks exceeded that of whites by a statistically significant 60% in an analysis that adjusted for several demographic and clinical features. The excess of strokes occurred at about the same rate in black women compared with white women, and in black men compared with white men, reported Dr. Patel, an electrophysiologist at the University of Pennsylvania in Philadelphia.
The implication is that because their stroke risk is greater, blacks with AF should especially receive appropriate stroke prophylaxis and AF therapy, he said. The overall findings also highlight the substantial stroke risk faced by all AF patients.
The data came from the University of Pennsylvania Atrial Fibrillation-Free study of 91,274 people who underwent an ECG examination in the University of Pennsylvania health system during 2004-2009 along with an index clinical encounter within 30 days. Excluding patients with a prevalent AF or other arrhythmia, prevalent stroke, or incomplete data left 56,835 AF- and stroke-free people to follow for incident AF, which occurred in 3,891 patients. At the time of AF diagnosis, the average age of patients was 63 years; more than a third had hypertension; a fifth had diabetes; and a fifth had heart failure. One-third of the incident-AF group was black, 58% were white, and the remainder were from other demographic groups.
Dr. Patel and his associates defined an AF-related stroke as any that occurred within 6 months before AF diagnosis or anytime after, which occurred in 645 (17%) of the incident-AF patients. The more than 50,000 AF-free people followed in the study had a total of 3,001 strokes not related to AF during follow-up, which meant that 18% of all strokes in the entire cohort were AF related.
Among the 645 AF-related strokes, roughly half occurred during the 6 months before AF diagnosis, and the other half following AF diagnosis. An analysis that focused exclusively on strokes that occurred after AF diagnosis showed that this subset of AF-associated strokes also occurred significantly more often in blacks than in whites.
Dr. Patel had no disclosures.
On Twitter @mitchelzoler
BOSTON – Black people with new-onset atrial fibrillation have a 60% increased risk for stroke compared with white people who have incident atrial fibrillation when not maintained on an appropriate anticlotting regimen, according to prospectively collected data from more than 56,000 subjects at a U.S. center.
But in the subgroup of new-onset atrial fibrillation (AF) patients who received appropriate treatment with aspirin or an anticoagulant, the stroke rates among white and blacks equalized. The analysis showed that 46% of the more than 3,000 people who developed AF during follow-up received aspirin if their CHA2DS2-VASc score was less than 2, or anticoagulation with warfarin or a new oral anticoagulant if their score was 2 or greater, Dr. Parin J. Patel said at the annual scientific sessions of the Heart Rhythm Society.
The majority of the followed cohort with incident atrial fibrillation did not receive this treatment, and in the total group, the relative rate of stroke among blacks exceeded that of whites by a statistically significant 60% in an analysis that adjusted for several demographic and clinical features. The excess of strokes occurred at about the same rate in black women compared with white women, and in black men compared with white men, reported Dr. Patel, an electrophysiologist at the University of Pennsylvania in Philadelphia.
The implication is that because their stroke risk is greater, blacks with AF should especially receive appropriate stroke prophylaxis and AF therapy, he said. The overall findings also highlight the substantial stroke risk faced by all AF patients.
The data came from the University of Pennsylvania Atrial Fibrillation-Free study of 91,274 people who underwent an ECG examination in the University of Pennsylvania health system during 2004-2009 along with an index clinical encounter within 30 days. Excluding patients with a prevalent AF or other arrhythmia, prevalent stroke, or incomplete data left 56,835 AF- and stroke-free people to follow for incident AF, which occurred in 3,891 patients. At the time of AF diagnosis, the average age of patients was 63 years; more than a third had hypertension; a fifth had diabetes; and a fifth had heart failure. One-third of the incident-AF group was black, 58% were white, and the remainder were from other demographic groups.
Dr. Patel and his associates defined an AF-related stroke as any that occurred within 6 months before AF diagnosis or anytime after, which occurred in 645 (17%) of the incident-AF patients. The more than 50,000 AF-free people followed in the study had a total of 3,001 strokes not related to AF during follow-up, which meant that 18% of all strokes in the entire cohort were AF related.
Among the 645 AF-related strokes, roughly half occurred during the 6 months before AF diagnosis, and the other half following AF diagnosis. An analysis that focused exclusively on strokes that occurred after AF diagnosis showed that this subset of AF-associated strokes also occurred significantly more often in blacks than in whites.
Dr. Patel had no disclosures.
On Twitter @mitchelzoler
AT HEART RHYTHM 2015
Key clinical point: Strokes associated with newly diagnosed atrial fibrillation were significantly more common in African American patients than in white patients.
Major finding: The rate of atrial fibrillation–associated stroke was 60% higher in black patients than in white patients.
Data source: A review of prospectively-collected data from 56,835 people who underwent a baseline ECG at one U.S. center during 2004-2009.
Disclosures: Dr. Patel had no disclosures.
VIDEO: Assessment tool rapidly screens lupus cognition
ROME – The Montreal Cognitive Assessment provides a quick and easy-to-use screening tool to identify patients with systemic lupus erythematosus with cognitive impairment, Dr. Zahi Touma reported in a poster at the European Congress of Rheumatology.
In a consecutive series of 78 patients screened with the Montreal Cognitive Assessment (MoCA), the free, single-page test, which can be administered in about 10 minutes, showed a sensitivity of 69% and specificity of 68%, compared with the current standard, the Hopkins Verbal Learning Test-Revised, said Dr. Touma, a rheumatologist at the University of Toronto.
Other easy-to-use and quick screening tools, such as the Mini-Mental State Examination, had substantially worse performance in the study. He and his associates found a sensitivity of 21% and specificity of 91% using the Mini-Mental State exam. For screening, higher sensitivity is desirable so that fewer patients with potential cognitive impairment are missed, he noted.
“Ease of use and time needed for assessment as well as appropriate psychometric properties make the MoCA the preferential screening test for cognitive impairment in patients with SLE,” Dr. Touma said in his poster.
Cognitive impairment is very common among patients with systemic lupus erythematosus (SLE). In this study, Dr Touma found a 47% prevalence using MoCA. Cognitive impairment, however, often goes unidentified in SLE patients, likely because of lack of awareness among rheumatologists as well as the absence of a quick and easily administered screening tool, he said in a video interview.
Dr. Touma said he hopes that the apparent efficacy of an easy-to-use screening tool like MoCA will help boost appreciation for the high prevalence of cognitive impairment in SLE patients. He suggested that clinicians screen for cognitive impairment as soon as SLE is diagnosed and that they perform follow-up screening during subsequent patient encounters with SLE patients who initially present without cognitive impairment.
Dr. Touma had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ROME – The Montreal Cognitive Assessment provides a quick and easy-to-use screening tool to identify patients with systemic lupus erythematosus with cognitive impairment, Dr. Zahi Touma reported in a poster at the European Congress of Rheumatology.
In a consecutive series of 78 patients screened with the Montreal Cognitive Assessment (MoCA), the free, single-page test, which can be administered in about 10 minutes, showed a sensitivity of 69% and specificity of 68%, compared with the current standard, the Hopkins Verbal Learning Test-Revised, said Dr. Touma, a rheumatologist at the University of Toronto.
Other easy-to-use and quick screening tools, such as the Mini-Mental State Examination, had substantially worse performance in the study. He and his associates found a sensitivity of 21% and specificity of 91% using the Mini-Mental State exam. For screening, higher sensitivity is desirable so that fewer patients with potential cognitive impairment are missed, he noted.
“Ease of use and time needed for assessment as well as appropriate psychometric properties make the MoCA the preferential screening test for cognitive impairment in patients with SLE,” Dr. Touma said in his poster.
Cognitive impairment is very common among patients with systemic lupus erythematosus (SLE). In this study, Dr Touma found a 47% prevalence using MoCA. Cognitive impairment, however, often goes unidentified in SLE patients, likely because of lack of awareness among rheumatologists as well as the absence of a quick and easily administered screening tool, he said in a video interview.
Dr. Touma said he hopes that the apparent efficacy of an easy-to-use screening tool like MoCA will help boost appreciation for the high prevalence of cognitive impairment in SLE patients. He suggested that clinicians screen for cognitive impairment as soon as SLE is diagnosed and that they perform follow-up screening during subsequent patient encounters with SLE patients who initially present without cognitive impairment.
Dr. Touma had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ROME – The Montreal Cognitive Assessment provides a quick and easy-to-use screening tool to identify patients with systemic lupus erythematosus with cognitive impairment, Dr. Zahi Touma reported in a poster at the European Congress of Rheumatology.
In a consecutive series of 78 patients screened with the Montreal Cognitive Assessment (MoCA), the free, single-page test, which can be administered in about 10 minutes, showed a sensitivity of 69% and specificity of 68%, compared with the current standard, the Hopkins Verbal Learning Test-Revised, said Dr. Touma, a rheumatologist at the University of Toronto.
Other easy-to-use and quick screening tools, such as the Mini-Mental State Examination, had substantially worse performance in the study. He and his associates found a sensitivity of 21% and specificity of 91% using the Mini-Mental State exam. For screening, higher sensitivity is desirable so that fewer patients with potential cognitive impairment are missed, he noted.
“Ease of use and time needed for assessment as well as appropriate psychometric properties make the MoCA the preferential screening test for cognitive impairment in patients with SLE,” Dr. Touma said in his poster.
Cognitive impairment is very common among patients with systemic lupus erythematosus (SLE). In this study, Dr Touma found a 47% prevalence using MoCA. Cognitive impairment, however, often goes unidentified in SLE patients, likely because of lack of awareness among rheumatologists as well as the absence of a quick and easily administered screening tool, he said in a video interview.
Dr. Touma said he hopes that the apparent efficacy of an easy-to-use screening tool like MoCA will help boost appreciation for the high prevalence of cognitive impairment in SLE patients. He suggested that clinicians screen for cognitive impairment as soon as SLE is diagnosed and that they perform follow-up screening during subsequent patient encounters with SLE patients who initially present without cognitive impairment.
Dr. Touma had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
AT THE EULAR 2015 CONGRESS
VIDEO: EULAR updates cardiovascular-disease risk recommendations
ROME – The European League Against Rheumatism introduced an update to its 2009 recommendations on assessing and managing cardiovascular-disease risk in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
The update features an expanded evidence base for the recommendations, especially for psoriatic arthritis and ankylosing spondylitis, Dr. Michael T. Nurmohamed said in an interview at the European Congress of Rheumatology. One new element in the revision included a scaling down of the previously suggested annual assessment to a more flexible approach to the timing of serial assessments based on the risk level of individual patients. Another addition is the possible use of carotid ultrasound to measure atherosclerotic burden as a complement to more routinely-measured risk factors such as blood pressure and serum lipids, said Dr. Nurmohamed, convener of the current task force as well as the panel that formulated the first version (Ann. Rheum. Dis. 2010;69:325-31).
A second EULAR task force recently developed new recommendations on assessing and managing other comorbidities in patients with rheumatologic diseases, such as osteoporosis, cancer, peptic ulcers, and renal dysfunction. Chronic kidney disease is an important modifier of cardiovascular-disease risk, and hence the new comorbidity recommendations complement the new cardiovascular-disease statement, said Dr. Nurmohamed, professor and head of the rheumatology research department at VU University Medical Center in Amsterdam.
Dr. Nurmohamed had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ROME – The European League Against Rheumatism introduced an update to its 2009 recommendations on assessing and managing cardiovascular-disease risk in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
The update features an expanded evidence base for the recommendations, especially for psoriatic arthritis and ankylosing spondylitis, Dr. Michael T. Nurmohamed said in an interview at the European Congress of Rheumatology. One new element in the revision included a scaling down of the previously suggested annual assessment to a more flexible approach to the timing of serial assessments based on the risk level of individual patients. Another addition is the possible use of carotid ultrasound to measure atherosclerotic burden as a complement to more routinely-measured risk factors such as blood pressure and serum lipids, said Dr. Nurmohamed, convener of the current task force as well as the panel that formulated the first version (Ann. Rheum. Dis. 2010;69:325-31).
A second EULAR task force recently developed new recommendations on assessing and managing other comorbidities in patients with rheumatologic diseases, such as osteoporosis, cancer, peptic ulcers, and renal dysfunction. Chronic kidney disease is an important modifier of cardiovascular-disease risk, and hence the new comorbidity recommendations complement the new cardiovascular-disease statement, said Dr. Nurmohamed, professor and head of the rheumatology research department at VU University Medical Center in Amsterdam.
Dr. Nurmohamed had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
ROME – The European League Against Rheumatism introduced an update to its 2009 recommendations on assessing and managing cardiovascular-disease risk in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
The update features an expanded evidence base for the recommendations, especially for psoriatic arthritis and ankylosing spondylitis, Dr. Michael T. Nurmohamed said in an interview at the European Congress of Rheumatology. One new element in the revision included a scaling down of the previously suggested annual assessment to a more flexible approach to the timing of serial assessments based on the risk level of individual patients. Another addition is the possible use of carotid ultrasound to measure atherosclerotic burden as a complement to more routinely-measured risk factors such as blood pressure and serum lipids, said Dr. Nurmohamed, convener of the current task force as well as the panel that formulated the first version (Ann. Rheum. Dis. 2010;69:325-31).
A second EULAR task force recently developed new recommendations on assessing and managing other comorbidities in patients with rheumatologic diseases, such as osteoporosis, cancer, peptic ulcers, and renal dysfunction. Chronic kidney disease is an important modifier of cardiovascular-disease risk, and hence the new comorbidity recommendations complement the new cardiovascular-disease statement, said Dr. Nurmohamed, professor and head of the rheumatology research department at VU University Medical Center in Amsterdam.
Dr. Nurmohamed had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
AT THE EULAR 2015 CONGRESS
Statins linked to better outcomes in hep C cirrhosis
VIENNA – Patients infected with hepatitis C virus who developed cirrhosis and received statin treatment had significantly lower rates of both death and cirrhosis decompensation, compared with cirrhosis patients who did not receive a statin in a confounder-adjusted analysis of data from more than 2,700 patients in a U.S. Department of Veterans Affairs database.
While this suggestive evidence is not strong enough to warrant routinely prescribing statins to cirrhosis patients, it does highlight the need to prescribe a statin to any cirrhosis patient who qualifies for the drug by standard criteria because of established cardiovascular disease or as part of primary prevention when there is elevated cardiovascular risk, Dr. Arpan Mohanty said at the meeting sponsored by the European Association for the Study of the Liver.
Conventional wisdom has often led to withholding statins from patients with liver disease out of concern for risk of statin-induced hepatotoxicity, said Dr. Mohanty, a gastroenterology researcher at Yale University in New Haven, Conn. But the new findings suggesting such overwhelming benefit from statin treatment in these patients indicates that “statin use should not be avoided” when patients with liver disease would otherwise qualify for statin treatment.
“Statins should be prescribed when required for atherosclerosis,” she said, adding that in New Haven her program has run sessions to educate primary care physicians on this.
The study used data collected during 1996-2009 by the Hepatitis C Virus Clinical Case Registry of the U.S. Department of Veterans Affairs, which includes more than 340,000 veterans, of whom more than 45,000 had been diagnosed with cirrhosis. Further analysis identified 1,323 eligible veterans from this group on statin treatment, and 12,522 not on statin treatment. Propensity score matching narrowed the study group down to 685 hepatitis C virus–infected veterans with cirrhosis who were on statin treatment, and 2,062 closely matched veterans infected with HCV and with cirrhosis but not receiving statin therapy.
The patients averaged 56 years old, 98% were men, and comorbidities were common; a third had a history of coronary artery disease, more than 80% had hypertension, more than half had diabetes, and more than half had alcohol dependency. Among patients with a serum cholesterol level greater than 200 mg/dL, 57% were not on a statin; among those with a serum low-density cholesterol level of about 160 mg/dL, 35% were not receiving a statin. “Statin use is low in patients with cirrhosis, even in those with high cardiovascular risk,” Dr. Mohanty said.
She and her associates tracked the incidence of death for a median of more than 2 years in these patients, and they followed new episodes of cirrhosis decompensation for nearly 2 years.
With adjustment for age, body mass index, serum albumin, and fibrosis-4 and MELD (Model for End-Stage Liver Disease) scores, the rates of both death and cirrhosis decompensation were each a statistically significant 45% lower among the patients on statins, compared with those not on a statin, they reported.
On Twitter @mitchelzoler
VIENNA – Patients infected with hepatitis C virus who developed cirrhosis and received statin treatment had significantly lower rates of both death and cirrhosis decompensation, compared with cirrhosis patients who did not receive a statin in a confounder-adjusted analysis of data from more than 2,700 patients in a U.S. Department of Veterans Affairs database.
While this suggestive evidence is not strong enough to warrant routinely prescribing statins to cirrhosis patients, it does highlight the need to prescribe a statin to any cirrhosis patient who qualifies for the drug by standard criteria because of established cardiovascular disease or as part of primary prevention when there is elevated cardiovascular risk, Dr. Arpan Mohanty said at the meeting sponsored by the European Association for the Study of the Liver.
Conventional wisdom has often led to withholding statins from patients with liver disease out of concern for risk of statin-induced hepatotoxicity, said Dr. Mohanty, a gastroenterology researcher at Yale University in New Haven, Conn. But the new findings suggesting such overwhelming benefit from statin treatment in these patients indicates that “statin use should not be avoided” when patients with liver disease would otherwise qualify for statin treatment.
“Statins should be prescribed when required for atherosclerosis,” she said, adding that in New Haven her program has run sessions to educate primary care physicians on this.
The study used data collected during 1996-2009 by the Hepatitis C Virus Clinical Case Registry of the U.S. Department of Veterans Affairs, which includes more than 340,000 veterans, of whom more than 45,000 had been diagnosed with cirrhosis. Further analysis identified 1,323 eligible veterans from this group on statin treatment, and 12,522 not on statin treatment. Propensity score matching narrowed the study group down to 685 hepatitis C virus–infected veterans with cirrhosis who were on statin treatment, and 2,062 closely matched veterans infected with HCV and with cirrhosis but not receiving statin therapy.
The patients averaged 56 years old, 98% were men, and comorbidities were common; a third had a history of coronary artery disease, more than 80% had hypertension, more than half had diabetes, and more than half had alcohol dependency. Among patients with a serum cholesterol level greater than 200 mg/dL, 57% were not on a statin; among those with a serum low-density cholesterol level of about 160 mg/dL, 35% were not receiving a statin. “Statin use is low in patients with cirrhosis, even in those with high cardiovascular risk,” Dr. Mohanty said.
She and her associates tracked the incidence of death for a median of more than 2 years in these patients, and they followed new episodes of cirrhosis decompensation for nearly 2 years.
With adjustment for age, body mass index, serum albumin, and fibrosis-4 and MELD (Model for End-Stage Liver Disease) scores, the rates of both death and cirrhosis decompensation were each a statistically significant 45% lower among the patients on statins, compared with those not on a statin, they reported.
On Twitter @mitchelzoler
VIENNA – Patients infected with hepatitis C virus who developed cirrhosis and received statin treatment had significantly lower rates of both death and cirrhosis decompensation, compared with cirrhosis patients who did not receive a statin in a confounder-adjusted analysis of data from more than 2,700 patients in a U.S. Department of Veterans Affairs database.
While this suggestive evidence is not strong enough to warrant routinely prescribing statins to cirrhosis patients, it does highlight the need to prescribe a statin to any cirrhosis patient who qualifies for the drug by standard criteria because of established cardiovascular disease or as part of primary prevention when there is elevated cardiovascular risk, Dr. Arpan Mohanty said at the meeting sponsored by the European Association for the Study of the Liver.
Conventional wisdom has often led to withholding statins from patients with liver disease out of concern for risk of statin-induced hepatotoxicity, said Dr. Mohanty, a gastroenterology researcher at Yale University in New Haven, Conn. But the new findings suggesting such overwhelming benefit from statin treatment in these patients indicates that “statin use should not be avoided” when patients with liver disease would otherwise qualify for statin treatment.
“Statins should be prescribed when required for atherosclerosis,” she said, adding that in New Haven her program has run sessions to educate primary care physicians on this.
The study used data collected during 1996-2009 by the Hepatitis C Virus Clinical Case Registry of the U.S. Department of Veterans Affairs, which includes more than 340,000 veterans, of whom more than 45,000 had been diagnosed with cirrhosis. Further analysis identified 1,323 eligible veterans from this group on statin treatment, and 12,522 not on statin treatment. Propensity score matching narrowed the study group down to 685 hepatitis C virus–infected veterans with cirrhosis who were on statin treatment, and 2,062 closely matched veterans infected with HCV and with cirrhosis but not receiving statin therapy.
The patients averaged 56 years old, 98% were men, and comorbidities were common; a third had a history of coronary artery disease, more than 80% had hypertension, more than half had diabetes, and more than half had alcohol dependency. Among patients with a serum cholesterol level greater than 200 mg/dL, 57% were not on a statin; among those with a serum low-density cholesterol level of about 160 mg/dL, 35% were not receiving a statin. “Statin use is low in patients with cirrhosis, even in those with high cardiovascular risk,” Dr. Mohanty said.
She and her associates tracked the incidence of death for a median of more than 2 years in these patients, and they followed new episodes of cirrhosis decompensation for nearly 2 years.
With adjustment for age, body mass index, serum albumin, and fibrosis-4 and MELD (Model for End-Stage Liver Disease) scores, the rates of both death and cirrhosis decompensation were each a statistically significant 45% lower among the patients on statins, compared with those not on a statin, they reported.
On Twitter @mitchelzoler
Unrecognized hepatitis C linked with advanced hepatic fibrosis
VIENNA – Roughly half of American adults with chronic hepatitis C infection are unaware of their infection, and about one-fifth of these people with unsuspected infection likely have advanced liver fibrosis, according to a new analysis of U.S. data.
These findings “strengthen the recommendation for hepatitis C virus (HCV) screening in asymptomatic individuals,” Dr. Prowpanga Udompap said at the meeting sponsored by the European Association for the Study of the Liver.
People infected by HCV with advanced liver fibrosis have top priority for receiving curative drug treatment, according to recommendations by the American Association for the Study of the Liver and the Infectious Diseases Society of America.
People who have HCV-associated liver fibrosis that goes untreated also risk having their infection become more refractory to cure over time, they risk progressive hepatic deterioration that will eventually become symptomatic, and they face increasing risk for developing liver cancer, noted Dr. W. Ray Kim, senior author of the study and professor of medicine and chief of gastroenterology and hepatology at Stanford (Calif.) University.
Dr. Kim said he was surprised that such a large percentage of Americans who have unrecognized HCV infection also probably have substantial hepatic damage. “To me it’s alarming that 20% of people who are not aware of their HCV infection are treatment candidates. These people are out there, but not getting treated,” he said in an interview.
Current U.S. HCV screening recommendations from the Centers for Disease Control and Prevention call for screening all Americans born during 1945-1965, “but there is no incentive to screen” and many U.S. primary care physicians don’t have HCV screening on their radar, he said.
The analysis conducted by Dr. Udompap and Dr. Kim used data collected by the National Health and Nutrition Examination Survey during 2001-2012, when the National Center for Health Statistics administered HCV testing to 45,000 of the 62,000 individuals who participated in the survey then.
Of the 45,000 people tested, 420 (0.9%) screened antibody positive and had infection confirmed by a second, RNA-based test. The HCV-positive patients then received a survey that included a question on whether they were aware of their HCV status before their current test result notification. One hundred sixty-three people (39%) completed and returned the survey: Eighty-three said they had previously been unaware they were HCV positive, and 80 said that they had known about their infection. The 50% rate of awareness of HCV chronic infection is consistent with a previously reported rate (Hepatology 2012;55:1652-61), said Dr. Udompap, a gastroenterology researcher at Stanford.
Individuals who were aware of their infection and those who were not had very similar demographic and clinical parameters. The average age was 53 years, and about two-thirds were men.
Dr. Udompap ran estimates of each respondent’s liver fibrosis and cirrhosis severity using the FIB-4 score and APRI score and data collected during the survey on age, liver enzyme levels, and platelet counts. These calculations showed that 22% of those ignorant of their HCV-positive status had a high probability of having advanced fibrosis, and 11% had a high probability of having cirrhosis, Dr. Udompap reported. These rates tracked close to those of the people who knew about their HCV-positive status, of whom 15% had a high probability of having advanced liver fibrosis and 11% were highly likely to have cirrhosis.
Dr. Udompap reported no financial disclosures. Dr. Kim has been a consultant to several drug companies that market, or are developing, drugs used in HCV.
On Twitter @mitchelzoler
VIENNA – Roughly half of American adults with chronic hepatitis C infection are unaware of their infection, and about one-fifth of these people with unsuspected infection likely have advanced liver fibrosis, according to a new analysis of U.S. data.
These findings “strengthen the recommendation for hepatitis C virus (HCV) screening in asymptomatic individuals,” Dr. Prowpanga Udompap said at the meeting sponsored by the European Association for the Study of the Liver.
People infected by HCV with advanced liver fibrosis have top priority for receiving curative drug treatment, according to recommendations by the American Association for the Study of the Liver and the Infectious Diseases Society of America.
People who have HCV-associated liver fibrosis that goes untreated also risk having their infection become more refractory to cure over time, they risk progressive hepatic deterioration that will eventually become symptomatic, and they face increasing risk for developing liver cancer, noted Dr. W. Ray Kim, senior author of the study and professor of medicine and chief of gastroenterology and hepatology at Stanford (Calif.) University.
Dr. Kim said he was surprised that such a large percentage of Americans who have unrecognized HCV infection also probably have substantial hepatic damage. “To me it’s alarming that 20% of people who are not aware of their HCV infection are treatment candidates. These people are out there, but not getting treated,” he said in an interview.
Current U.S. HCV screening recommendations from the Centers for Disease Control and Prevention call for screening all Americans born during 1945-1965, “but there is no incentive to screen” and many U.S. primary care physicians don’t have HCV screening on their radar, he said.
The analysis conducted by Dr. Udompap and Dr. Kim used data collected by the National Health and Nutrition Examination Survey during 2001-2012, when the National Center for Health Statistics administered HCV testing to 45,000 of the 62,000 individuals who participated in the survey then.
Of the 45,000 people tested, 420 (0.9%) screened antibody positive and had infection confirmed by a second, RNA-based test. The HCV-positive patients then received a survey that included a question on whether they were aware of their HCV status before their current test result notification. One hundred sixty-three people (39%) completed and returned the survey: Eighty-three said they had previously been unaware they were HCV positive, and 80 said that they had known about their infection. The 50% rate of awareness of HCV chronic infection is consistent with a previously reported rate (Hepatology 2012;55:1652-61), said Dr. Udompap, a gastroenterology researcher at Stanford.
Individuals who were aware of their infection and those who were not had very similar demographic and clinical parameters. The average age was 53 years, and about two-thirds were men.
Dr. Udompap ran estimates of each respondent’s liver fibrosis and cirrhosis severity using the FIB-4 score and APRI score and data collected during the survey on age, liver enzyme levels, and platelet counts. These calculations showed that 22% of those ignorant of their HCV-positive status had a high probability of having advanced fibrosis, and 11% had a high probability of having cirrhosis, Dr. Udompap reported. These rates tracked close to those of the people who knew about their HCV-positive status, of whom 15% had a high probability of having advanced liver fibrosis and 11% were highly likely to have cirrhosis.
Dr. Udompap reported no financial disclosures. Dr. Kim has been a consultant to several drug companies that market, or are developing, drugs used in HCV.
On Twitter @mitchelzoler
VIENNA – Roughly half of American adults with chronic hepatitis C infection are unaware of their infection, and about one-fifth of these people with unsuspected infection likely have advanced liver fibrosis, according to a new analysis of U.S. data.
These findings “strengthen the recommendation for hepatitis C virus (HCV) screening in asymptomatic individuals,” Dr. Prowpanga Udompap said at the meeting sponsored by the European Association for the Study of the Liver.
People infected by HCV with advanced liver fibrosis have top priority for receiving curative drug treatment, according to recommendations by the American Association for the Study of the Liver and the Infectious Diseases Society of America.
People who have HCV-associated liver fibrosis that goes untreated also risk having their infection become more refractory to cure over time, they risk progressive hepatic deterioration that will eventually become symptomatic, and they face increasing risk for developing liver cancer, noted Dr. W. Ray Kim, senior author of the study and professor of medicine and chief of gastroenterology and hepatology at Stanford (Calif.) University.
Dr. Kim said he was surprised that such a large percentage of Americans who have unrecognized HCV infection also probably have substantial hepatic damage. “To me it’s alarming that 20% of people who are not aware of their HCV infection are treatment candidates. These people are out there, but not getting treated,” he said in an interview.
Current U.S. HCV screening recommendations from the Centers for Disease Control and Prevention call for screening all Americans born during 1945-1965, “but there is no incentive to screen” and many U.S. primary care physicians don’t have HCV screening on their radar, he said.
The analysis conducted by Dr. Udompap and Dr. Kim used data collected by the National Health and Nutrition Examination Survey during 2001-2012, when the National Center for Health Statistics administered HCV testing to 45,000 of the 62,000 individuals who participated in the survey then.
Of the 45,000 people tested, 420 (0.9%) screened antibody positive and had infection confirmed by a second, RNA-based test. The HCV-positive patients then received a survey that included a question on whether they were aware of their HCV status before their current test result notification. One hundred sixty-three people (39%) completed and returned the survey: Eighty-three said they had previously been unaware they were HCV positive, and 80 said that they had known about their infection. The 50% rate of awareness of HCV chronic infection is consistent with a previously reported rate (Hepatology 2012;55:1652-61), said Dr. Udompap, a gastroenterology researcher at Stanford.
Individuals who were aware of their infection and those who were not had very similar demographic and clinical parameters. The average age was 53 years, and about two-thirds were men.
Dr. Udompap ran estimates of each respondent’s liver fibrosis and cirrhosis severity using the FIB-4 score and APRI score and data collected during the survey on age, liver enzyme levels, and platelet counts. These calculations showed that 22% of those ignorant of their HCV-positive status had a high probability of having advanced fibrosis, and 11% had a high probability of having cirrhosis, Dr. Udompap reported. These rates tracked close to those of the people who knew about their HCV-positive status, of whom 15% had a high probability of having advanced liver fibrosis and 11% were highly likely to have cirrhosis.
Dr. Udompap reported no financial disclosures. Dr. Kim has been a consultant to several drug companies that market, or are developing, drugs used in HCV.
On Twitter @mitchelzoler
Key clinical point: One-fifth of Americans with unrecognized chronic hepatitis C infection likely have advanced hepatic fibrosis.
Major finding: Among U.S. adults with unrecognized chronic hepatitis C infection, 22% had laboratory results indicating a high probability of advanced hepatic fibrosis.
Data source: Data collected from 420 Americans found to have a chronic hepatitis C infection in the National Health and Nutrition Examination Survey during 2001-2012.
Disclosures: Dr. Udompap reported having no financial disclosures. Dr. Kim has been a consultant to several drug companies that market or develop drugs to eradicate hepatitis C infections.
HRS: A fib Plus Hemodialysis Equals No Benefit From Warfarin
BOSTON – Patients with atrial fibrillation who also require hemodialysis receive no added antistroke benefit from warfarin treatment and may be more likely to have a major bleeding episode while on warfarin, based on a retrospective study of 302 patients at a single U.S. center.
“The safety and effectiveness of warfarin in patients with atrial fibrillation and chronic hemodialysis is questionable,” Dr. Lohit Garg said at the annual scientific sessions of the Heart Rhythm Society.
Dr. Garg noted that about 90% of patients in the review received aspirin, and they would also receive heparin three times a week as part of their hemodialysis protocol. ”It’s a good hypothesis” that aspirin plus heparin during hemodialysis might provide enough anticoagulation, but without warfarin the rate of stroke or transient ischemic attack was “pretty high,” 11%, “higher than [in] the general population, so aspirin and heparin may not be enough,” he said. The thromboembolic event rate with warfarin was 8%, not a statistically significant difference.
Dr. Garg and his associates reviewed patient charts at Beaumont Health System in Royal Oak, Mich., from 2009 to 2012 to find patients on chronic hemodialysis just diagnosed with new-onset atrial fibrillation (AF), and patients with chronic AF newly started on hemodialysis. They identified 724 such patients, and narrowed this down to 302 when they excluded those with valve disease or prosthesis, venous thromboembolic disease, coagulation or bleeding disorder, cancer, renal transplant, and a few other exclusions.
The study group included 119 patients (39%) who received warfarin and 183 (61%) who did not, at the discretion of their treating physicians. Patients averaged 77 years of age, and those who received warfarin and those who didn’t showed roughly similar rates of comorbidities, with no statistically significant differences between the two subgroups.
During an average follow-up of 2 years, the rates of thromboembolic events showed no statistically significant difference between the patients on warfarin and those not receiving the drug. Major bleeds occurred in 22% of the warfarin patients and 14% of those not on warfarin, a relative 53% increased risk with warfarin use that approached but did not reach statistical significance, reported Dr. Garg of the Heart Rhythm Center of Beaumont Hospital in Royal Oak, Mich.
Further, the major bleed subcategory of intracranial bleeds occurred in 10% of patients on warfarin and 4% of those off warfarin, a greater than doubled rate with warfarin, again a difference that approached but did achieve statistical significance. All the intracranial bleeds were fatal.
Dr. Garg also highlighted that these were high-risk patients, with 1.8-year average survival, and a median survival of about 2 years for both patients on warfarin and those off. During follow-up that extended as long as 5 years, 80% of patients died with similar mortality rates in the two treatment subgroups, 82% for those on warfarin and 79% for those who did not receive warfarin.
“We as cardiologists tend to prescribe warfarin” to patients like these, “but obviously we have to rethink this because it seems to harm patients without adding benefit,” commented Dr. Philipp Sommer, an electrophysiologist at the University of Leipzig (Germany).
Dr. Garg had no relevant financial disclosures.
BOSTON – Patients with atrial fibrillation who also require hemodialysis receive no added antistroke benefit from warfarin treatment and may be more likely to have a major bleeding episode while on warfarin, based on a retrospective study of 302 patients at a single U.S. center.
“The safety and effectiveness of warfarin in patients with atrial fibrillation and chronic hemodialysis is questionable,” Dr. Lohit Garg said at the annual scientific sessions of the Heart Rhythm Society.
Dr. Garg noted that about 90% of patients in the review received aspirin, and they would also receive heparin three times a week as part of their hemodialysis protocol. ”It’s a good hypothesis” that aspirin plus heparin during hemodialysis might provide enough anticoagulation, but without warfarin the rate of stroke or transient ischemic attack was “pretty high,” 11%, “higher than [in] the general population, so aspirin and heparin may not be enough,” he said. The thromboembolic event rate with warfarin was 8%, not a statistically significant difference.
Dr. Garg and his associates reviewed patient charts at Beaumont Health System in Royal Oak, Mich., from 2009 to 2012 to find patients on chronic hemodialysis just diagnosed with new-onset atrial fibrillation (AF), and patients with chronic AF newly started on hemodialysis. They identified 724 such patients, and narrowed this down to 302 when they excluded those with valve disease or prosthesis, venous thromboembolic disease, coagulation or bleeding disorder, cancer, renal transplant, and a few other exclusions.
The study group included 119 patients (39%) who received warfarin and 183 (61%) who did not, at the discretion of their treating physicians. Patients averaged 77 years of age, and those who received warfarin and those who didn’t showed roughly similar rates of comorbidities, with no statistically significant differences between the two subgroups.
During an average follow-up of 2 years, the rates of thromboembolic events showed no statistically significant difference between the patients on warfarin and those not receiving the drug. Major bleeds occurred in 22% of the warfarin patients and 14% of those not on warfarin, a relative 53% increased risk with warfarin use that approached but did not reach statistical significance, reported Dr. Garg of the Heart Rhythm Center of Beaumont Hospital in Royal Oak, Mich.
Further, the major bleed subcategory of intracranial bleeds occurred in 10% of patients on warfarin and 4% of those off warfarin, a greater than doubled rate with warfarin, again a difference that approached but did achieve statistical significance. All the intracranial bleeds were fatal.
Dr. Garg also highlighted that these were high-risk patients, with 1.8-year average survival, and a median survival of about 2 years for both patients on warfarin and those off. During follow-up that extended as long as 5 years, 80% of patients died with similar mortality rates in the two treatment subgroups, 82% for those on warfarin and 79% for those who did not receive warfarin.
“We as cardiologists tend to prescribe warfarin” to patients like these, “but obviously we have to rethink this because it seems to harm patients without adding benefit,” commented Dr. Philipp Sommer, an electrophysiologist at the University of Leipzig (Germany).
Dr. Garg had no relevant financial disclosures.
BOSTON – Patients with atrial fibrillation who also require hemodialysis receive no added antistroke benefit from warfarin treatment and may be more likely to have a major bleeding episode while on warfarin, based on a retrospective study of 302 patients at a single U.S. center.
“The safety and effectiveness of warfarin in patients with atrial fibrillation and chronic hemodialysis is questionable,” Dr. Lohit Garg said at the annual scientific sessions of the Heart Rhythm Society.
Dr. Garg noted that about 90% of patients in the review received aspirin, and they would also receive heparin three times a week as part of their hemodialysis protocol. ”It’s a good hypothesis” that aspirin plus heparin during hemodialysis might provide enough anticoagulation, but without warfarin the rate of stroke or transient ischemic attack was “pretty high,” 11%, “higher than [in] the general population, so aspirin and heparin may not be enough,” he said. The thromboembolic event rate with warfarin was 8%, not a statistically significant difference.
Dr. Garg and his associates reviewed patient charts at Beaumont Health System in Royal Oak, Mich., from 2009 to 2012 to find patients on chronic hemodialysis just diagnosed with new-onset atrial fibrillation (AF), and patients with chronic AF newly started on hemodialysis. They identified 724 such patients, and narrowed this down to 302 when they excluded those with valve disease or prosthesis, venous thromboembolic disease, coagulation or bleeding disorder, cancer, renal transplant, and a few other exclusions.
The study group included 119 patients (39%) who received warfarin and 183 (61%) who did not, at the discretion of their treating physicians. Patients averaged 77 years of age, and those who received warfarin and those who didn’t showed roughly similar rates of comorbidities, with no statistically significant differences between the two subgroups.
During an average follow-up of 2 years, the rates of thromboembolic events showed no statistically significant difference between the patients on warfarin and those not receiving the drug. Major bleeds occurred in 22% of the warfarin patients and 14% of those not on warfarin, a relative 53% increased risk with warfarin use that approached but did not reach statistical significance, reported Dr. Garg of the Heart Rhythm Center of Beaumont Hospital in Royal Oak, Mich.
Further, the major bleed subcategory of intracranial bleeds occurred in 10% of patients on warfarin and 4% of those off warfarin, a greater than doubled rate with warfarin, again a difference that approached but did achieve statistical significance. All the intracranial bleeds were fatal.
Dr. Garg also highlighted that these were high-risk patients, with 1.8-year average survival, and a median survival of about 2 years for both patients on warfarin and those off. During follow-up that extended as long as 5 years, 80% of patients died with similar mortality rates in the two treatment subgroups, 82% for those on warfarin and 79% for those who did not receive warfarin.
“We as cardiologists tend to prescribe warfarin” to patients like these, “but obviously we have to rethink this because it seems to harm patients without adding benefit,” commented Dr. Philipp Sommer, an electrophysiologist at the University of Leipzig (Germany).
Dr. Garg had no relevant financial disclosures.
AT HEART RHYTHM 2015
