User login
Step therapy and biologics: An easier road ahead?
Laws recently passed or under consideration in state legislatures may offer some relief to physicians and patients dogged by the “step” or “fail-first” therapy protocols mandated by insurers, but until better clinical evidence is available to support treatment decisions and biosimilars reduce costs, clinicians must strategize to get patients through the step pathways as fast as possible.
Rheumatologists, gastroenterologists, and dermatologists all confront fail-first policies in their practices, particularly when prescribing the biologic agents that have been game changers in treating rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, among other diseases.
In RA, for example, a patient might be required to fail a series of disease-modifying antirheumatic drugs (DMARDs), including methotrexate, before starting a biologic. In Crohn’s disease, patients might have to first fail on steroids and immunosuppressants.
Most clinicians consider cost concerns fair as a basis for insurance decisions. But they can also have strong rationales for making exceptions. This may mean starting patients on a biologic early, particularly those they deem unlikely to respond to first- or second-line treatments – which may be cheaper but are not necessarily safer.
In egregious cases, a patient already stable on a biologic who has changed insurance plans may be forced to go backwards in the treatment pathway, and fail first- and second-line therapies all over again before resuming – a process unlikely to be cost-effective in the long term, and also rife with ethical concerns, say clinicians.
“Making a patient fail to get a less toxic drug sort of violates our ‘do no harm’ principle,” Dr. Stephen B. Hanauer, medical director of the Digestive Health Center at Northwestern University, Chicago, said in an interview.
“I always say that if biologics cost a dollar, we’d be using them for everybody. If you take away the steroids and the immunosuppressants, these are very safe drugs for IBD, far safer than steroids – but steroids are cheap,” Dr. Hanauer said.
And with some debilitating disease presentations, such as severe Crohn’s, “being told that we have to try conventional therapies and the patient has to fail them can mean putting the patient through progression of their disease, and suffering,” Dr. David T. Rubin, codirector of the Digestive Diseases Center at the University of Chicago, said in an interview. “We really struggle with this.”
Dr. Joseph S. Eastern, a dermatologist practicing in Belleville, N.J., said his specialty faces similar challenges with step therapy. “Dermatologists as a group are pretty risk averse. When given the opportunity, we do an excellent job of prescribing conventional medications, ultraviolet therapy, and biologics in the most cost-efficient possible way,” he said in an email.
Yet “third-party payers tell us, for example, that a patient must fail methotrexate before we can use a biologic, when the whole advantage of biologic therapy for many of these patients is the avoidance of organotoxicity and other serious risks.”
As a result, Dr. Eastern said, “I write a lot more vehement letters to payers about the biologics these days.”
Choice vs. cost
Rheumatologists are among the clinicians most affected by fail-first and step therapy mandates, as the diseases they treat – particularly RA – are the most established indications for biologic therapies, and for which the largest number of these are approved.
Though Medicare and Medicaid allow physicians considerable leeway, private insurers often tightly circumscribe the timing and choice of biologics in RA. As insurers’ first-choice biologic drug changes frequently, and varies from plan to plan, a patient who is stable on one agent might be asked to switch to another, a phenomenon known as nonmedical switching.
Insurers are seldom transparent about their reasons for establishing certain biologic drugs as their go-to agents, clinicians say, while making it difficult for physicians to prescribe others. “There’s a tremendous amount of discounting going on that we are oblivious to as physicians. I’ve seen situations where drug A is the first one you have to use this month and the next month, drug C,” said Dr. Norman Gaylis, a rheumatologist practicing in Aventura, Fla.
Attempting to start a patient on a nonpreferential biologic will generate paperwork and delays, Dr. Gaylis said, which can cost patients valuable time. “There’s a window of opportunity to treat these diseases, and by creating a step therapy pathway we’re closing the window at least partially.”
“As an example, rituximab in most payer plans is not tiered as a first-line biologic treatment option despite the fact that there are frequent scenarios where the clinical and serological presentation of a patient would suggest it to be preferable as a first-line treatment choice over an anti-TNF [tumor necrosis factor],” Dr. Gaylis said.
“There is no room for clinical decision making based upon the unique presentation of each different patient when choosing the best treatment option,” he said.
Rheumatologists often become overwhelmed with authorization paperwork, “and still in many instances end up with a denial of their request.”
Dr. Karen Kolba, a rheumatologist in private practice in Santa Maria, Calif., said that she agreed in principle with the way step therapy protocols have been established, and that some of the frustration with step therapy amounts to a tendency among specialist clinicians to bristle at being told what to do.
“Physicians hate protocol,” Dr. Kolba said. “But comparing one protocol to another is the only way we are going to make advances.” It took the rheumatology community about 30 years to come to terms with the use of methotrexate in RA, she noted, and the stepped approach grew naturally from the treatment of methotrexate failures with biologic agents when these first emerged in the late 1990s.
A majority of RA patients started on a stepped approach using DMARDs will respond, Dr. Kolba said, and for those who must move into the biologic realm, the vast majority will succeed on the first anti-TNF agent prescribed. And there is little science to establish that one TNF inhibitor is superior – only that patients can sometimes succeed with one and fail another.
“As far as which biologic to initiate, my personal opinion is I don’t care, and I tell the patients that I don’t mind if the insurer picks out of this category because I’m flipping a coin as well,” she said.
Step mandates become objectionable, Dr. Kolba said, when they are purportedly based in science that doesn’t exist, or when they seem to exist only to wear down the provider.
“With private insurance not only do they have the drug of the year, they’re going to make me battle for every single prescription. When I say I have tried this patient on maximal tolerable doses of all these DMARDs, they ought to believe me. Yet I get six-page forms back saying, ‘Give me the start and stop dates of all the drugs you’ve used.’”
States constrain fail first
For many specialists treating patients with biologics, some of these hurdles are already getting lowered.
Concerns about physician choice, a lack of transparency in insurer decision making, and the ethics of forcing patients to fail have led advocacy groups to press hard in recent years for legislation limiting step therapy – with successes in a dozen states.
While the state legislation is not disease or drug specific, it has important implications for clinicians treating with biologics. “Step therapy in its genesis was a good idea – it’s OK to try to reduce costs in the health care system,” said Patrick Stone, state government relations manager at the National Psoriasis Foundation in Annapolis, Md., a group that works extensively on step therapy issues. “But when these protocols were first crafted, medications like biologics weren’t in use.”
Jeff Okazaki, associate director of the Coalition of State Rheumatology Organizations, a group based in Schaumberg, Ill., said lawmakers are starting to accept that in terms of cost of care, “somebody not being treated appropriately and down the line has organ damage or comorbidity because of incorrect treatment decisions due to step therapy is a higher burden.”
Moreover, he said, “we’d seen protocols requiring five or more steps, and for each step you have to try it at least 90 days.” For a patient with rheumatic or autoimmune disease, “getting through something like that can just be devastating.”
In 2011, Connecticut, Mississippi, and Arkansas became the first states to pass legislation limiting some aspect of step therapy. Since then, nine additional states have passed legislation varying in focus and scope.
In Kentucky, for example, patients cannot be forced by their insurer to remain on an ineffective therapy for more than 30 days, and insurers must respond to physician requests for an override within 2 days. Mississippi allows physicians to override insurer decisions with proof of clinical evidence. In California, legislation passed last year aims to reduce bureaucracy and speed up response to physician requests for overrides.
Mr. Stone and Mr. Okazaki are working in a coalition with other dermatology, rheumatology, and GI groups to push bills in seven more states, including New York, North Carolina, and Ohio.
While all the bills differ in what they attempt to limit, the model legislation has three basic objectives, Mr. Okazaki said. “We want a clear set of clinical guidelines, a quick review process, and overrides that allow for exceptions in cases where patients shouldn’t have to go through step therapy.”
Clinical strategies and research gaps
New legislation undoubtedly will help providers and patients get access to their choice of treatment agents. But so long as biologics are expensive – and it will be a while before the first biosimilar drugs, which will have efficacy and safety similar to their reference biologics, reduce prices in any meaningful way – step therapy will likely remain the norm.
One of the key difficulties providers face when pushing back on an insurer in favor of a biologic drug is insufficient clinical evidence.
With IBD, Dr. Rubin said, “we need a need more longitudinal understanding” and better prognostic indicators “in order to justify spending the extra money or going to one of these therapies.”
Dr. Hanauer said one of the limitations he faces in practice is insufficient clinical evidence for biologics early in the treatment pathway for IBD.
RA “is much more common than Crohn’s disease is. In trials, it’s much easier to recruit hundreds of patients [for an RA trial], while with Crohn’s it’s very hard to enroll more than a couple a year at most sites,” he said. “And as you move earlier in the treatment pathway that becomes somewhat more difficult as well.”
His solution for now, he said, is to follow established step pathways in an accelerated way, for “a rapid transition toward highly effective therapies” without having to face extensive pushback from insurers.
“The idea is to initiate immunosuppressants for any patients with sufficient disease activity to justify steroids,” Dr. Hanauer said. “Their steroids are then tapered, and while on immunosuppressants, patients are in a perfect setup to get combination therapy with an immunosuppressive and a biologic – and that’s a 2- to 3-month transition, not 2-3 years.”
Dr. Kolba said that despite the wide array of options for treating RA, the specialty suffers from a dearth of understanding as to why some patients fail drugs while others succeed, even within the same drug class.
Rheumatologists’ prescribing choices would be highly influenced by better biomarkers, were they to become available, she said. And they’d have far better arguments when confronted with payer pushback.
“We’re all looking for that magic biologic marker to tell me which drug to use,” Dr. Kolba said, “because God knows if I had a blood test that said ‘this is the drug,’ I would go to the mat with the insurer.”
AGA Resource
AGA offers an IBD Clinical Service line to provide GIs with the tools needed to be more efficient, understand quality standards, receive appropriate reimbursements and improve the process of care for their patients with IBD at www.gastro.org/practice/clinical-service-line/ibd-clinical-service-line.
Laws recently passed or under consideration in state legislatures may offer some relief to physicians and patients dogged by the “step” or “fail-first” therapy protocols mandated by insurers, but until better clinical evidence is available to support treatment decisions and biosimilars reduce costs, clinicians must strategize to get patients through the step pathways as fast as possible.
Rheumatologists, gastroenterologists, and dermatologists all confront fail-first policies in their practices, particularly when prescribing the biologic agents that have been game changers in treating rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, among other diseases.
In RA, for example, a patient might be required to fail a series of disease-modifying antirheumatic drugs (DMARDs), including methotrexate, before starting a biologic. In Crohn’s disease, patients might have to first fail on steroids and immunosuppressants.
Most clinicians consider cost concerns fair as a basis for insurance decisions. But they can also have strong rationales for making exceptions. This may mean starting patients on a biologic early, particularly those they deem unlikely to respond to first- or second-line treatments – which may be cheaper but are not necessarily safer.
In egregious cases, a patient already stable on a biologic who has changed insurance plans may be forced to go backwards in the treatment pathway, and fail first- and second-line therapies all over again before resuming – a process unlikely to be cost-effective in the long term, and also rife with ethical concerns, say clinicians.
“Making a patient fail to get a less toxic drug sort of violates our ‘do no harm’ principle,” Dr. Stephen B. Hanauer, medical director of the Digestive Health Center at Northwestern University, Chicago, said in an interview.
“I always say that if biologics cost a dollar, we’d be using them for everybody. If you take away the steroids and the immunosuppressants, these are very safe drugs for IBD, far safer than steroids – but steroids are cheap,” Dr. Hanauer said.
And with some debilitating disease presentations, such as severe Crohn’s, “being told that we have to try conventional therapies and the patient has to fail them can mean putting the patient through progression of their disease, and suffering,” Dr. David T. Rubin, codirector of the Digestive Diseases Center at the University of Chicago, said in an interview. “We really struggle with this.”
Dr. Joseph S. Eastern, a dermatologist practicing in Belleville, N.J., said his specialty faces similar challenges with step therapy. “Dermatologists as a group are pretty risk averse. When given the opportunity, we do an excellent job of prescribing conventional medications, ultraviolet therapy, and biologics in the most cost-efficient possible way,” he said in an email.
Yet “third-party payers tell us, for example, that a patient must fail methotrexate before we can use a biologic, when the whole advantage of biologic therapy for many of these patients is the avoidance of organotoxicity and other serious risks.”
As a result, Dr. Eastern said, “I write a lot more vehement letters to payers about the biologics these days.”
Choice vs. cost
Rheumatologists are among the clinicians most affected by fail-first and step therapy mandates, as the diseases they treat – particularly RA – are the most established indications for biologic therapies, and for which the largest number of these are approved.
Though Medicare and Medicaid allow physicians considerable leeway, private insurers often tightly circumscribe the timing and choice of biologics in RA. As insurers’ first-choice biologic drug changes frequently, and varies from plan to plan, a patient who is stable on one agent might be asked to switch to another, a phenomenon known as nonmedical switching.
Insurers are seldom transparent about their reasons for establishing certain biologic drugs as their go-to agents, clinicians say, while making it difficult for physicians to prescribe others. “There’s a tremendous amount of discounting going on that we are oblivious to as physicians. I’ve seen situations where drug A is the first one you have to use this month and the next month, drug C,” said Dr. Norman Gaylis, a rheumatologist practicing in Aventura, Fla.
Attempting to start a patient on a nonpreferential biologic will generate paperwork and delays, Dr. Gaylis said, which can cost patients valuable time. “There’s a window of opportunity to treat these diseases, and by creating a step therapy pathway we’re closing the window at least partially.”
“As an example, rituximab in most payer plans is not tiered as a first-line biologic treatment option despite the fact that there are frequent scenarios where the clinical and serological presentation of a patient would suggest it to be preferable as a first-line treatment choice over an anti-TNF [tumor necrosis factor],” Dr. Gaylis said.
“There is no room for clinical decision making based upon the unique presentation of each different patient when choosing the best treatment option,” he said.
Rheumatologists often become overwhelmed with authorization paperwork, “and still in many instances end up with a denial of their request.”
Dr. Karen Kolba, a rheumatologist in private practice in Santa Maria, Calif., said that she agreed in principle with the way step therapy protocols have been established, and that some of the frustration with step therapy amounts to a tendency among specialist clinicians to bristle at being told what to do.
“Physicians hate protocol,” Dr. Kolba said. “But comparing one protocol to another is the only way we are going to make advances.” It took the rheumatology community about 30 years to come to terms with the use of methotrexate in RA, she noted, and the stepped approach grew naturally from the treatment of methotrexate failures with biologic agents when these first emerged in the late 1990s.
A majority of RA patients started on a stepped approach using DMARDs will respond, Dr. Kolba said, and for those who must move into the biologic realm, the vast majority will succeed on the first anti-TNF agent prescribed. And there is little science to establish that one TNF inhibitor is superior – only that patients can sometimes succeed with one and fail another.
“As far as which biologic to initiate, my personal opinion is I don’t care, and I tell the patients that I don’t mind if the insurer picks out of this category because I’m flipping a coin as well,” she said.
Step mandates become objectionable, Dr. Kolba said, when they are purportedly based in science that doesn’t exist, or when they seem to exist only to wear down the provider.
“With private insurance not only do they have the drug of the year, they’re going to make me battle for every single prescription. When I say I have tried this patient on maximal tolerable doses of all these DMARDs, they ought to believe me. Yet I get six-page forms back saying, ‘Give me the start and stop dates of all the drugs you’ve used.’”
States constrain fail first
For many specialists treating patients with biologics, some of these hurdles are already getting lowered.
Concerns about physician choice, a lack of transparency in insurer decision making, and the ethics of forcing patients to fail have led advocacy groups to press hard in recent years for legislation limiting step therapy – with successes in a dozen states.
While the state legislation is not disease or drug specific, it has important implications for clinicians treating with biologics. “Step therapy in its genesis was a good idea – it’s OK to try to reduce costs in the health care system,” said Patrick Stone, state government relations manager at the National Psoriasis Foundation in Annapolis, Md., a group that works extensively on step therapy issues. “But when these protocols were first crafted, medications like biologics weren’t in use.”
Jeff Okazaki, associate director of the Coalition of State Rheumatology Organizations, a group based in Schaumberg, Ill., said lawmakers are starting to accept that in terms of cost of care, “somebody not being treated appropriately and down the line has organ damage or comorbidity because of incorrect treatment decisions due to step therapy is a higher burden.”
Moreover, he said, “we’d seen protocols requiring five or more steps, and for each step you have to try it at least 90 days.” For a patient with rheumatic or autoimmune disease, “getting through something like that can just be devastating.”
In 2011, Connecticut, Mississippi, and Arkansas became the first states to pass legislation limiting some aspect of step therapy. Since then, nine additional states have passed legislation varying in focus and scope.
In Kentucky, for example, patients cannot be forced by their insurer to remain on an ineffective therapy for more than 30 days, and insurers must respond to physician requests for an override within 2 days. Mississippi allows physicians to override insurer decisions with proof of clinical evidence. In California, legislation passed last year aims to reduce bureaucracy and speed up response to physician requests for overrides.
Mr. Stone and Mr. Okazaki are working in a coalition with other dermatology, rheumatology, and GI groups to push bills in seven more states, including New York, North Carolina, and Ohio.
While all the bills differ in what they attempt to limit, the model legislation has three basic objectives, Mr. Okazaki said. “We want a clear set of clinical guidelines, a quick review process, and overrides that allow for exceptions in cases where patients shouldn’t have to go through step therapy.”
Clinical strategies and research gaps
New legislation undoubtedly will help providers and patients get access to their choice of treatment agents. But so long as biologics are expensive – and it will be a while before the first biosimilar drugs, which will have efficacy and safety similar to their reference biologics, reduce prices in any meaningful way – step therapy will likely remain the norm.
One of the key difficulties providers face when pushing back on an insurer in favor of a biologic drug is insufficient clinical evidence.
With IBD, Dr. Rubin said, “we need a need more longitudinal understanding” and better prognostic indicators “in order to justify spending the extra money or going to one of these therapies.”
Dr. Hanauer said one of the limitations he faces in practice is insufficient clinical evidence for biologics early in the treatment pathway for IBD.
RA “is much more common than Crohn’s disease is. In trials, it’s much easier to recruit hundreds of patients [for an RA trial], while with Crohn’s it’s very hard to enroll more than a couple a year at most sites,” he said. “And as you move earlier in the treatment pathway that becomes somewhat more difficult as well.”
His solution for now, he said, is to follow established step pathways in an accelerated way, for “a rapid transition toward highly effective therapies” without having to face extensive pushback from insurers.
“The idea is to initiate immunosuppressants for any patients with sufficient disease activity to justify steroids,” Dr. Hanauer said. “Their steroids are then tapered, and while on immunosuppressants, patients are in a perfect setup to get combination therapy with an immunosuppressive and a biologic – and that’s a 2- to 3-month transition, not 2-3 years.”
Dr. Kolba said that despite the wide array of options for treating RA, the specialty suffers from a dearth of understanding as to why some patients fail drugs while others succeed, even within the same drug class.
Rheumatologists’ prescribing choices would be highly influenced by better biomarkers, were they to become available, she said. And they’d have far better arguments when confronted with payer pushback.
“We’re all looking for that magic biologic marker to tell me which drug to use,” Dr. Kolba said, “because God knows if I had a blood test that said ‘this is the drug,’ I would go to the mat with the insurer.”
AGA Resource
AGA offers an IBD Clinical Service line to provide GIs with the tools needed to be more efficient, understand quality standards, receive appropriate reimbursements and improve the process of care for their patients with IBD at www.gastro.org/practice/clinical-service-line/ibd-clinical-service-line.
Laws recently passed or under consideration in state legislatures may offer some relief to physicians and patients dogged by the “step” or “fail-first” therapy protocols mandated by insurers, but until better clinical evidence is available to support treatment decisions and biosimilars reduce costs, clinicians must strategize to get patients through the step pathways as fast as possible.
Rheumatologists, gastroenterologists, and dermatologists all confront fail-first policies in their practices, particularly when prescribing the biologic agents that have been game changers in treating rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, among other diseases.
In RA, for example, a patient might be required to fail a series of disease-modifying antirheumatic drugs (DMARDs), including methotrexate, before starting a biologic. In Crohn’s disease, patients might have to first fail on steroids and immunosuppressants.
Most clinicians consider cost concerns fair as a basis for insurance decisions. But they can also have strong rationales for making exceptions. This may mean starting patients on a biologic early, particularly those they deem unlikely to respond to first- or second-line treatments – which may be cheaper but are not necessarily safer.
In egregious cases, a patient already stable on a biologic who has changed insurance plans may be forced to go backwards in the treatment pathway, and fail first- and second-line therapies all over again before resuming – a process unlikely to be cost-effective in the long term, and also rife with ethical concerns, say clinicians.
“Making a patient fail to get a less toxic drug sort of violates our ‘do no harm’ principle,” Dr. Stephen B. Hanauer, medical director of the Digestive Health Center at Northwestern University, Chicago, said in an interview.
“I always say that if biologics cost a dollar, we’d be using them for everybody. If you take away the steroids and the immunosuppressants, these are very safe drugs for IBD, far safer than steroids – but steroids are cheap,” Dr. Hanauer said.
And with some debilitating disease presentations, such as severe Crohn’s, “being told that we have to try conventional therapies and the patient has to fail them can mean putting the patient through progression of their disease, and suffering,” Dr. David T. Rubin, codirector of the Digestive Diseases Center at the University of Chicago, said in an interview. “We really struggle with this.”
Dr. Joseph S. Eastern, a dermatologist practicing in Belleville, N.J., said his specialty faces similar challenges with step therapy. “Dermatologists as a group are pretty risk averse. When given the opportunity, we do an excellent job of prescribing conventional medications, ultraviolet therapy, and biologics in the most cost-efficient possible way,” he said in an email.
Yet “third-party payers tell us, for example, that a patient must fail methotrexate before we can use a biologic, when the whole advantage of biologic therapy for many of these patients is the avoidance of organotoxicity and other serious risks.”
As a result, Dr. Eastern said, “I write a lot more vehement letters to payers about the biologics these days.”
Choice vs. cost
Rheumatologists are among the clinicians most affected by fail-first and step therapy mandates, as the diseases they treat – particularly RA – are the most established indications for biologic therapies, and for which the largest number of these are approved.
Though Medicare and Medicaid allow physicians considerable leeway, private insurers often tightly circumscribe the timing and choice of biologics in RA. As insurers’ first-choice biologic drug changes frequently, and varies from plan to plan, a patient who is stable on one agent might be asked to switch to another, a phenomenon known as nonmedical switching.
Insurers are seldom transparent about their reasons for establishing certain biologic drugs as their go-to agents, clinicians say, while making it difficult for physicians to prescribe others. “There’s a tremendous amount of discounting going on that we are oblivious to as physicians. I’ve seen situations where drug A is the first one you have to use this month and the next month, drug C,” said Dr. Norman Gaylis, a rheumatologist practicing in Aventura, Fla.
Attempting to start a patient on a nonpreferential biologic will generate paperwork and delays, Dr. Gaylis said, which can cost patients valuable time. “There’s a window of opportunity to treat these diseases, and by creating a step therapy pathway we’re closing the window at least partially.”
“As an example, rituximab in most payer plans is not tiered as a first-line biologic treatment option despite the fact that there are frequent scenarios where the clinical and serological presentation of a patient would suggest it to be preferable as a first-line treatment choice over an anti-TNF [tumor necrosis factor],” Dr. Gaylis said.
“There is no room for clinical decision making based upon the unique presentation of each different patient when choosing the best treatment option,” he said.
Rheumatologists often become overwhelmed with authorization paperwork, “and still in many instances end up with a denial of their request.”
Dr. Karen Kolba, a rheumatologist in private practice in Santa Maria, Calif., said that she agreed in principle with the way step therapy protocols have been established, and that some of the frustration with step therapy amounts to a tendency among specialist clinicians to bristle at being told what to do.
“Physicians hate protocol,” Dr. Kolba said. “But comparing one protocol to another is the only way we are going to make advances.” It took the rheumatology community about 30 years to come to terms with the use of methotrexate in RA, she noted, and the stepped approach grew naturally from the treatment of methotrexate failures with biologic agents when these first emerged in the late 1990s.
A majority of RA patients started on a stepped approach using DMARDs will respond, Dr. Kolba said, and for those who must move into the biologic realm, the vast majority will succeed on the first anti-TNF agent prescribed. And there is little science to establish that one TNF inhibitor is superior – only that patients can sometimes succeed with one and fail another.
“As far as which biologic to initiate, my personal opinion is I don’t care, and I tell the patients that I don’t mind if the insurer picks out of this category because I’m flipping a coin as well,” she said.
Step mandates become objectionable, Dr. Kolba said, when they are purportedly based in science that doesn’t exist, or when they seem to exist only to wear down the provider.
“With private insurance not only do they have the drug of the year, they’re going to make me battle for every single prescription. When I say I have tried this patient on maximal tolerable doses of all these DMARDs, they ought to believe me. Yet I get six-page forms back saying, ‘Give me the start and stop dates of all the drugs you’ve used.’”
States constrain fail first
For many specialists treating patients with biologics, some of these hurdles are already getting lowered.
Concerns about physician choice, a lack of transparency in insurer decision making, and the ethics of forcing patients to fail have led advocacy groups to press hard in recent years for legislation limiting step therapy – with successes in a dozen states.
While the state legislation is not disease or drug specific, it has important implications for clinicians treating with biologics. “Step therapy in its genesis was a good idea – it’s OK to try to reduce costs in the health care system,” said Patrick Stone, state government relations manager at the National Psoriasis Foundation in Annapolis, Md., a group that works extensively on step therapy issues. “But when these protocols were first crafted, medications like biologics weren’t in use.”
Jeff Okazaki, associate director of the Coalition of State Rheumatology Organizations, a group based in Schaumberg, Ill., said lawmakers are starting to accept that in terms of cost of care, “somebody not being treated appropriately and down the line has organ damage or comorbidity because of incorrect treatment decisions due to step therapy is a higher burden.”
Moreover, he said, “we’d seen protocols requiring five or more steps, and for each step you have to try it at least 90 days.” For a patient with rheumatic or autoimmune disease, “getting through something like that can just be devastating.”
In 2011, Connecticut, Mississippi, and Arkansas became the first states to pass legislation limiting some aspect of step therapy. Since then, nine additional states have passed legislation varying in focus and scope.
In Kentucky, for example, patients cannot be forced by their insurer to remain on an ineffective therapy for more than 30 days, and insurers must respond to physician requests for an override within 2 days. Mississippi allows physicians to override insurer decisions with proof of clinical evidence. In California, legislation passed last year aims to reduce bureaucracy and speed up response to physician requests for overrides.
Mr. Stone and Mr. Okazaki are working in a coalition with other dermatology, rheumatology, and GI groups to push bills in seven more states, including New York, North Carolina, and Ohio.
While all the bills differ in what they attempt to limit, the model legislation has three basic objectives, Mr. Okazaki said. “We want a clear set of clinical guidelines, a quick review process, and overrides that allow for exceptions in cases where patients shouldn’t have to go through step therapy.”
Clinical strategies and research gaps
New legislation undoubtedly will help providers and patients get access to their choice of treatment agents. But so long as biologics are expensive – and it will be a while before the first biosimilar drugs, which will have efficacy and safety similar to their reference biologics, reduce prices in any meaningful way – step therapy will likely remain the norm.
One of the key difficulties providers face when pushing back on an insurer in favor of a biologic drug is insufficient clinical evidence.
With IBD, Dr. Rubin said, “we need a need more longitudinal understanding” and better prognostic indicators “in order to justify spending the extra money or going to one of these therapies.”
Dr. Hanauer said one of the limitations he faces in practice is insufficient clinical evidence for biologics early in the treatment pathway for IBD.
RA “is much more common than Crohn’s disease is. In trials, it’s much easier to recruit hundreds of patients [for an RA trial], while with Crohn’s it’s very hard to enroll more than a couple a year at most sites,” he said. “And as you move earlier in the treatment pathway that becomes somewhat more difficult as well.”
His solution for now, he said, is to follow established step pathways in an accelerated way, for “a rapid transition toward highly effective therapies” without having to face extensive pushback from insurers.
“The idea is to initiate immunosuppressants for any patients with sufficient disease activity to justify steroids,” Dr. Hanauer said. “Their steroids are then tapered, and while on immunosuppressants, patients are in a perfect setup to get combination therapy with an immunosuppressive and a biologic – and that’s a 2- to 3-month transition, not 2-3 years.”
Dr. Kolba said that despite the wide array of options for treating RA, the specialty suffers from a dearth of understanding as to why some patients fail drugs while others succeed, even within the same drug class.
Rheumatologists’ prescribing choices would be highly influenced by better biomarkers, were they to become available, she said. And they’d have far better arguments when confronted with payer pushback.
“We’re all looking for that magic biologic marker to tell me which drug to use,” Dr. Kolba said, “because God knows if I had a blood test that said ‘this is the drug,’ I would go to the mat with the insurer.”
AGA Resource
AGA offers an IBD Clinical Service line to provide GIs with the tools needed to be more efficient, understand quality standards, receive appropriate reimbursements and improve the process of care for their patients with IBD at www.gastro.org/practice/clinical-service-line/ibd-clinical-service-line.
Step therapy and biologics: An easier road ahead?
Laws recently passed or under consideration in state legislatures may offer some relief to physicians and patients dogged by the “step” or “fail-first” therapy protocols mandated by insurers, but until better clinical evidence is available to support treatment decisions and biosimilars reduce costs, clinicians must strategize to get patients through the step pathways as fast as possible.
Rheumatologists, gastroenterologists, and dermatologists all confront fail-first policies in their practices, particularly when prescribing the biologic agents that have been game changers in treating rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, among other diseases.
In RA, for example, a patient might be required to fail a series of disease-modifying antirheumatic drugs (DMARDs), including methotrexate, before starting a biologic. In Crohn’s disease, patients might have to first fail on steroids and immunosuppressants.
Most clinicians consider cost concerns fair as a basis for insurance decisions. But they can also have strong rationales for making exceptions. This may mean starting patients on a biologic early, particularly those they deem unlikely to respond to first- or second-line treatments – which may be cheaper but are not necessarily safer.
In egregious cases, a patient already stable on a biologic who has changed insurance plans may be forced to go backwards in the treatment pathway, and fail first- and second-line therapies all over again before resuming – a process unlikely to be cost-effective in the long term, and also rife with ethical concerns, say clinicians.
“Making a patient fail to get a less toxic drug sort of violates our ‘do no harm’ principle,” Dr. Stephen B. Hanauer, medical director of the Digestive Health Center at Northwestern University, Chicago, said in an interview.
“I always say that if biologics cost a dollar, we’d be using them for everybody. If you take away the steroids and the immunosuppressants, these are very safe drugs for IBD, far safer than steroids – but steroids are cheap,” Dr. Hanauer said.
And with some debilitating disease presentations, such as severe Crohn’s, “being told that we have to try conventional therapies and the patient has to fail them can mean putting the patient through progression of their disease, and suffering,” Dr. David T. Rubin, codirector of the Digestive Diseases Center at the University of Chicago, said in an interview. “We really struggle with this.”
Dr. Joseph S. Eastern, a dermatologist practicing in Belleville, N.J., said his specialty faces similar challenges with step therapy. “Dermatologists as a group are pretty risk averse. When given the opportunity, we do an excellent job of prescribing conventional medications, ultraviolet therapy, and biologics in the most cost-efficient possible way,” he said in an email.
Yet “third-party payers tell us, for example, that a patient must fail methotrexate before we can use a biologic, when the whole advantage of biologic therapy for many of these patients is the avoidance of organotoxicity and other serious risks.”
As a result, Dr. Eastern said, “I write a lot more vehement letters to payers about the biologics these days.”
Choice vs. cost
Rheumatologists are among the clinicians most affected by fail-first and step therapy mandates, as the diseases they treat – particularly RA – are the most established indications for biologic therapies, and for which the largest number of these are approved.
Though Medicare and Medicaid allow physicians considerable leeway, private insurers often tightly circumscribe the timing and choice of biologics in RA. As insurers’ first-choice biologic drug changes frequently, and varies from plan to plan, a patient who is stable on one agent might be asked to switch to another, a phenomenon known as nonmedical switching.
Insurers are seldom transparent about their reasons for establishing certain biologic drugs as their go-to agents, clinicians say, while making it difficult for physicians to prescribe others. “There’s a tremendous amount of discounting going on that we are oblivious to as physicians. I’ve seen situations where drug A is the first one you have to use this month and the next month, drug C,” said Dr. Norman Gaylis, a rheumatologist practicing in Aventura, Fla.
Attempting to start a patient on a nonpreferential biologic will generate paperwork and delays, Dr. Gaylis said, which can cost patients valuable time. “There’s a window of opportunity to treat these diseases, and by creating a step therapy pathway we’re closing the window at least partially.”
“As an example, rituximab in most payer plans is not tiered as a first-line biologic treatment option despite the fact that there are frequent scenarios where the clinical and serological presentation of a patient would suggest it to be preferable as a first-line treatment choice over an anti-TNF [tumor necrosis factor],” Dr. Gaylis said.
“There is no room for clinical decision making based upon the unique presentation of each different patient when choosing the best treatment option,” he said.
Rheumatologists often become overwhelmed with authorization paperwork, “and still in many instances end up with a denial of their request.”
Dr. Karen Kolba, a rheumatologist in private practice in Santa Maria, Calif., said that she agreed in principle with the way step therapy protocols have been established, and that some of the frustration with step therapy amounts to a tendency among specialist clinicians to bristle at being told what to do.
“Physicians hate protocol,” Dr. Kolba said. “But comparing one protocol to another is the only way we are going to make advances.” It took the rheumatology community about 30 years to come to terms with the use of methotrexate in RA, she noted, and the stepped approach grew naturally from the treatment of methotrexate failures with biologic agents when these first emerged in the late 1990s.
A majority of RA patients started on a stepped approach using DMARDs will respond, Dr. Kolba said, and for those who must move into the biologic realm, the vast majority will succeed on the first anti-TNF agent prescribed. And there is little science to establish that one TNF inhibitor is superior – only that patients can sometimes succeed with one and fail another.
“As far as which biologic to initiate, my personal opinion is I don’t care, and I tell the patients that I don’t mind if the insurer picks out of this category because I’m flipping a coin as well,” she said.
Step mandates become objectionable, Dr. Kolba said, when they are purportedly based in science that doesn’t exist, or when they seem to exist only to wear down the provider.
“With private insurance not only do they have the drug of the year, they’re going to make me battle for every single prescription. When I say I have tried this patient on maximal tolerable doses of all these DMARDs, they ought to believe me. Yet I get six-page forms back saying, ‘Give me the start and stop dates of all the drugs you’ve used.’”
States constrain fail first
For many specialists treating patients with biologics, some of these hurdles are already getting lowered.
Concerns about physician choice, a lack of transparency in insurer decision making, and the ethics of forcing patients to fail have led advocacy groups to press hard in recent years for legislation limiting step therapy – with successes in a dozen states.
While the state legislation is not disease or drug specific, it has important implications for clinicians treating with biologics. “Step therapy in its genesis was a good idea – it’s OK to try to reduce costs in the health care system,” said Patrick Stone, state government relations manager at the National Psoriasis Foundation in Annapolis, Md., a group that works extensively on step therapy issues. “But when these protocols were first crafted, medications like biologics weren’t in use.”
Jeff Okazaki, associate director of the Coalition of State Rheumatology Organizations, a group based in Schaumberg, Ill., said lawmakers are starting to accept that in terms of cost of care, “somebody not being treated appropriately and down the line has organ damage or comorbidity because of incorrect treatment decisions due to step therapy is a higher burden.”
Moreover, he said, “we’d seen protocols requiring five or more steps, and for each step you have to try it at least 90 days.” For a patient with rheumatic or autoimmune disease, “getting through something like that can just be devastating.”
In 2011, Connecticut, Mississippi, and Arkansas became the first states to pass legislation limiting some aspect of step therapy. Since then, nine additional states have passed legislation varying in focus and scope.
In Kentucky, for example, patients cannot be forced by their insurer to remain on an ineffective therapy for more than 30 days, and insurers must respond to physician requests for an override within 2 days. Mississippi allows physicians to override insurer decisions with proof of clinical evidence. In California, legislation passed last year aims to reduce bureaucracy and speed up response to physician requests for overrides.
Mr. Stone and Mr. Okazaki are working in a coalition with other dermatology, rheumatology, and GI groups to push bills in seven more states, including New York, North Carolina, and Ohio.
While all the bills differ in what they attempt to limit, the model legislation has three basic objectives, Mr. Okazaki said. “We want a clear set of clinical guidelines, a quick review process, and overrides that allow for exceptions in cases where patients shouldn’t have to go through step therapy.”
Clinical strategies and research gaps
New legislation undoubtedly will help providers and patients get access to their choice of treatment agents. But so long as biologics are expensive – and it will be a while before the first biosimilar drugs, which will have efficacy and safety similar to their reference biologics, reduce prices in any meaningful way – step therapy will likely remain the norm.
One of the key difficulties providers face when pushing back on an insurer in favor of a biologic drug is insufficient clinical evidence.
With IBD, Dr. Rubin said, “we need a need more longitudinal understanding” and better prognostic indicators “in order to justify spending the extra money or going to one of these therapies.”
Dr. Hanauer said one of the limitations he faces in practice is insufficient clinical evidence for biologics early in the treatment pathway for IBD.
RA “is much more common than Crohn’s disease is. In trials, it’s much easier to recruit hundreds of patients [for an RA trial], while with Crohn’s it’s very hard to enroll more than a couple a year at most sites,” he said. “And as you move earlier in the treatment pathway that becomes somewhat more difficult as well.”
His solution for now, he said, is to follow established step pathways in an accelerated way, for “a rapid transition toward highly effective therapies” without having to face extensive pushback from insurers.
“The idea is to initiate immunosuppressants for any patients with sufficient disease activity to justify steroids,” Dr. Hanauer said. “Their steroids are then tapered, and while on immunosuppressants, patients are in a perfect setup to get combination therapy with an immunosuppressive and a biologic – and that’s a 2- to 3-month transition, not 2-3 years.”
Dr. Kolba said that despite the wide array of options for treating RA, the specialty suffers from a dearth of understanding as to why some patients fail drugs while others succeed, even within the same drug class.
Rheumatologists’ prescribing choices would be highly influenced by better biomarkers, were they to become available, she said. And they’d have far better arguments when confronted with payer pushback.
“We’re all looking for that magic biologic marker to tell me which drug to use,” Dr. Kolba said, “because God knows if I had a blood test that said ‘this is the drug,’ I would go to the mat with the insurer.”
Laws recently passed or under consideration in state legislatures may offer some relief to physicians and patients dogged by the “step” or “fail-first” therapy protocols mandated by insurers, but until better clinical evidence is available to support treatment decisions and biosimilars reduce costs, clinicians must strategize to get patients through the step pathways as fast as possible.
Rheumatologists, gastroenterologists, and dermatologists all confront fail-first policies in their practices, particularly when prescribing the biologic agents that have been game changers in treating rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, among other diseases.
In RA, for example, a patient might be required to fail a series of disease-modifying antirheumatic drugs (DMARDs), including methotrexate, before starting a biologic. In Crohn’s disease, patients might have to first fail on steroids and immunosuppressants.
Most clinicians consider cost concerns fair as a basis for insurance decisions. But they can also have strong rationales for making exceptions. This may mean starting patients on a biologic early, particularly those they deem unlikely to respond to first- or second-line treatments – which may be cheaper but are not necessarily safer.
In egregious cases, a patient already stable on a biologic who has changed insurance plans may be forced to go backwards in the treatment pathway, and fail first- and second-line therapies all over again before resuming – a process unlikely to be cost-effective in the long term, and also rife with ethical concerns, say clinicians.
“Making a patient fail to get a less toxic drug sort of violates our ‘do no harm’ principle,” Dr. Stephen B. Hanauer, medical director of the Digestive Health Center at Northwestern University, Chicago, said in an interview.
“I always say that if biologics cost a dollar, we’d be using them for everybody. If you take away the steroids and the immunosuppressants, these are very safe drugs for IBD, far safer than steroids – but steroids are cheap,” Dr. Hanauer said.
And with some debilitating disease presentations, such as severe Crohn’s, “being told that we have to try conventional therapies and the patient has to fail them can mean putting the patient through progression of their disease, and suffering,” Dr. David T. Rubin, codirector of the Digestive Diseases Center at the University of Chicago, said in an interview. “We really struggle with this.”
Dr. Joseph S. Eastern, a dermatologist practicing in Belleville, N.J., said his specialty faces similar challenges with step therapy. “Dermatologists as a group are pretty risk averse. When given the opportunity, we do an excellent job of prescribing conventional medications, ultraviolet therapy, and biologics in the most cost-efficient possible way,” he said in an email.
Yet “third-party payers tell us, for example, that a patient must fail methotrexate before we can use a biologic, when the whole advantage of biologic therapy for many of these patients is the avoidance of organotoxicity and other serious risks.”
As a result, Dr. Eastern said, “I write a lot more vehement letters to payers about the biologics these days.”
Choice vs. cost
Rheumatologists are among the clinicians most affected by fail-first and step therapy mandates, as the diseases they treat – particularly RA – are the most established indications for biologic therapies, and for which the largest number of these are approved.
Though Medicare and Medicaid allow physicians considerable leeway, private insurers often tightly circumscribe the timing and choice of biologics in RA. As insurers’ first-choice biologic drug changes frequently, and varies from plan to plan, a patient who is stable on one agent might be asked to switch to another, a phenomenon known as nonmedical switching.
Insurers are seldom transparent about their reasons for establishing certain biologic drugs as their go-to agents, clinicians say, while making it difficult for physicians to prescribe others. “There’s a tremendous amount of discounting going on that we are oblivious to as physicians. I’ve seen situations where drug A is the first one you have to use this month and the next month, drug C,” said Dr. Norman Gaylis, a rheumatologist practicing in Aventura, Fla.
Attempting to start a patient on a nonpreferential biologic will generate paperwork and delays, Dr. Gaylis said, which can cost patients valuable time. “There’s a window of opportunity to treat these diseases, and by creating a step therapy pathway we’re closing the window at least partially.”
“As an example, rituximab in most payer plans is not tiered as a first-line biologic treatment option despite the fact that there are frequent scenarios where the clinical and serological presentation of a patient would suggest it to be preferable as a first-line treatment choice over an anti-TNF [tumor necrosis factor],” Dr. Gaylis said.
“There is no room for clinical decision making based upon the unique presentation of each different patient when choosing the best treatment option,” he said.
Rheumatologists often become overwhelmed with authorization paperwork, “and still in many instances end up with a denial of their request.”
Dr. Karen Kolba, a rheumatologist in private practice in Santa Maria, Calif., said that she agreed in principle with the way step therapy protocols have been established, and that some of the frustration with step therapy amounts to a tendency among specialist clinicians to bristle at being told what to do.
“Physicians hate protocol,” Dr. Kolba said. “But comparing one protocol to another is the only way we are going to make advances.” It took the rheumatology community about 30 years to come to terms with the use of methotrexate in RA, she noted, and the stepped approach grew naturally from the treatment of methotrexate failures with biologic agents when these first emerged in the late 1990s.
A majority of RA patients started on a stepped approach using DMARDs will respond, Dr. Kolba said, and for those who must move into the biologic realm, the vast majority will succeed on the first anti-TNF agent prescribed. And there is little science to establish that one TNF inhibitor is superior – only that patients can sometimes succeed with one and fail another.
“As far as which biologic to initiate, my personal opinion is I don’t care, and I tell the patients that I don’t mind if the insurer picks out of this category because I’m flipping a coin as well,” she said.
Step mandates become objectionable, Dr. Kolba said, when they are purportedly based in science that doesn’t exist, or when they seem to exist only to wear down the provider.
“With private insurance not only do they have the drug of the year, they’re going to make me battle for every single prescription. When I say I have tried this patient on maximal tolerable doses of all these DMARDs, they ought to believe me. Yet I get six-page forms back saying, ‘Give me the start and stop dates of all the drugs you’ve used.’”
States constrain fail first
For many specialists treating patients with biologics, some of these hurdles are already getting lowered.
Concerns about physician choice, a lack of transparency in insurer decision making, and the ethics of forcing patients to fail have led advocacy groups to press hard in recent years for legislation limiting step therapy – with successes in a dozen states.
While the state legislation is not disease or drug specific, it has important implications for clinicians treating with biologics. “Step therapy in its genesis was a good idea – it’s OK to try to reduce costs in the health care system,” said Patrick Stone, state government relations manager at the National Psoriasis Foundation in Annapolis, Md., a group that works extensively on step therapy issues. “But when these protocols were first crafted, medications like biologics weren’t in use.”
Jeff Okazaki, associate director of the Coalition of State Rheumatology Organizations, a group based in Schaumberg, Ill., said lawmakers are starting to accept that in terms of cost of care, “somebody not being treated appropriately and down the line has organ damage or comorbidity because of incorrect treatment decisions due to step therapy is a higher burden.”
Moreover, he said, “we’d seen protocols requiring five or more steps, and for each step you have to try it at least 90 days.” For a patient with rheumatic or autoimmune disease, “getting through something like that can just be devastating.”
In 2011, Connecticut, Mississippi, and Arkansas became the first states to pass legislation limiting some aspect of step therapy. Since then, nine additional states have passed legislation varying in focus and scope.
In Kentucky, for example, patients cannot be forced by their insurer to remain on an ineffective therapy for more than 30 days, and insurers must respond to physician requests for an override within 2 days. Mississippi allows physicians to override insurer decisions with proof of clinical evidence. In California, legislation passed last year aims to reduce bureaucracy and speed up response to physician requests for overrides.
Mr. Stone and Mr. Okazaki are working in a coalition with other dermatology, rheumatology, and GI groups to push bills in seven more states, including New York, North Carolina, and Ohio.
While all the bills differ in what they attempt to limit, the model legislation has three basic objectives, Mr. Okazaki said. “We want a clear set of clinical guidelines, a quick review process, and overrides that allow for exceptions in cases where patients shouldn’t have to go through step therapy.”
Clinical strategies and research gaps
New legislation undoubtedly will help providers and patients get access to their choice of treatment agents. But so long as biologics are expensive – and it will be a while before the first biosimilar drugs, which will have efficacy and safety similar to their reference biologics, reduce prices in any meaningful way – step therapy will likely remain the norm.
One of the key difficulties providers face when pushing back on an insurer in favor of a biologic drug is insufficient clinical evidence.
With IBD, Dr. Rubin said, “we need a need more longitudinal understanding” and better prognostic indicators “in order to justify spending the extra money or going to one of these therapies.”
Dr. Hanauer said one of the limitations he faces in practice is insufficient clinical evidence for biologics early in the treatment pathway for IBD.
RA “is much more common than Crohn’s disease is. In trials, it’s much easier to recruit hundreds of patients [for an RA trial], while with Crohn’s it’s very hard to enroll more than a couple a year at most sites,” he said. “And as you move earlier in the treatment pathway that becomes somewhat more difficult as well.”
His solution for now, he said, is to follow established step pathways in an accelerated way, for “a rapid transition toward highly effective therapies” without having to face extensive pushback from insurers.
“The idea is to initiate immunosuppressants for any patients with sufficient disease activity to justify steroids,” Dr. Hanauer said. “Their steroids are then tapered, and while on immunosuppressants, patients are in a perfect setup to get combination therapy with an immunosuppressive and a biologic – and that’s a 2- to 3-month transition, not 2-3 years.”
Dr. Kolba said that despite the wide array of options for treating RA, the specialty suffers from a dearth of understanding as to why some patients fail drugs while others succeed, even within the same drug class.
Rheumatologists’ prescribing choices would be highly influenced by better biomarkers, were they to become available, she said. And they’d have far better arguments when confronted with payer pushback.
“We’re all looking for that magic biologic marker to tell me which drug to use,” Dr. Kolba said, “because God knows if I had a blood test that said ‘this is the drug,’ I would go to the mat with the insurer.”
Laws recently passed or under consideration in state legislatures may offer some relief to physicians and patients dogged by the “step” or “fail-first” therapy protocols mandated by insurers, but until better clinical evidence is available to support treatment decisions and biosimilars reduce costs, clinicians must strategize to get patients through the step pathways as fast as possible.
Rheumatologists, gastroenterologists, and dermatologists all confront fail-first policies in their practices, particularly when prescribing the biologic agents that have been game changers in treating rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, among other diseases.
In RA, for example, a patient might be required to fail a series of disease-modifying antirheumatic drugs (DMARDs), including methotrexate, before starting a biologic. In Crohn’s disease, patients might have to first fail on steroids and immunosuppressants.
Most clinicians consider cost concerns fair as a basis for insurance decisions. But they can also have strong rationales for making exceptions. This may mean starting patients on a biologic early, particularly those they deem unlikely to respond to first- or second-line treatments – which may be cheaper but are not necessarily safer.
In egregious cases, a patient already stable on a biologic who has changed insurance plans may be forced to go backwards in the treatment pathway, and fail first- and second-line therapies all over again before resuming – a process unlikely to be cost-effective in the long term, and also rife with ethical concerns, say clinicians.
“Making a patient fail to get a less toxic drug sort of violates our ‘do no harm’ principle,” Dr. Stephen B. Hanauer, medical director of the Digestive Health Center at Northwestern University, Chicago, said in an interview.
“I always say that if biologics cost a dollar, we’d be using them for everybody. If you take away the steroids and the immunosuppressants, these are very safe drugs for IBD, far safer than steroids – but steroids are cheap,” Dr. Hanauer said.
And with some debilitating disease presentations, such as severe Crohn’s, “being told that we have to try conventional therapies and the patient has to fail them can mean putting the patient through progression of their disease, and suffering,” Dr. David T. Rubin, codirector of the Digestive Diseases Center at the University of Chicago, said in an interview. “We really struggle with this.”
Dr. Joseph S. Eastern, a dermatologist practicing in Belleville, N.J., said his specialty faces similar challenges with step therapy. “Dermatologists as a group are pretty risk averse. When given the opportunity, we do an excellent job of prescribing conventional medications, ultraviolet therapy, and biologics in the most cost-efficient possible way,” he said in an email.
Yet “third-party payers tell us, for example, that a patient must fail methotrexate before we can use a biologic, when the whole advantage of biologic therapy for many of these patients is the avoidance of organotoxicity and other serious risks.”
As a result, Dr. Eastern said, “I write a lot more vehement letters to payers about the biologics these days.”
Choice vs. cost
Rheumatologists are among the clinicians most affected by fail-first and step therapy mandates, as the diseases they treat – particularly RA – are the most established indications for biologic therapies, and for which the largest number of these are approved.
Though Medicare and Medicaid allow physicians considerable leeway, private insurers often tightly circumscribe the timing and choice of biologics in RA. As insurers’ first-choice biologic drug changes frequently, and varies from plan to plan, a patient who is stable on one agent might be asked to switch to another, a phenomenon known as nonmedical switching.
Insurers are seldom transparent about their reasons for establishing certain biologic drugs as their go-to agents, clinicians say, while making it difficult for physicians to prescribe others. “There’s a tremendous amount of discounting going on that we are oblivious to as physicians. I’ve seen situations where drug A is the first one you have to use this month and the next month, drug C,” said Dr. Norman Gaylis, a rheumatologist practicing in Aventura, Fla.
Attempting to start a patient on a nonpreferential biologic will generate paperwork and delays, Dr. Gaylis said, which can cost patients valuable time. “There’s a window of opportunity to treat these diseases, and by creating a step therapy pathway we’re closing the window at least partially.”
“As an example, rituximab in most payer plans is not tiered as a first-line biologic treatment option despite the fact that there are frequent scenarios where the clinical and serological presentation of a patient would suggest it to be preferable as a first-line treatment choice over an anti-TNF [tumor necrosis factor],” Dr. Gaylis said.
“There is no room for clinical decision making based upon the unique presentation of each different patient when choosing the best treatment option,” he said.
Rheumatologists often become overwhelmed with authorization paperwork, “and still in many instances end up with a denial of their request.”
Dr. Karen Kolba, a rheumatologist in private practice in Santa Maria, Calif., said that she agreed in principle with the way step therapy protocols have been established, and that some of the frustration with step therapy amounts to a tendency among specialist clinicians to bristle at being told what to do.
“Physicians hate protocol,” Dr. Kolba said. “But comparing one protocol to another is the only way we are going to make advances.” It took the rheumatology community about 30 years to come to terms with the use of methotrexate in RA, she noted, and the stepped approach grew naturally from the treatment of methotrexate failures with biologic agents when these first emerged in the late 1990s.
A majority of RA patients started on a stepped approach using DMARDs will respond, Dr. Kolba said, and for those who must move into the biologic realm, the vast majority will succeed on the first anti-TNF agent prescribed. And there is little science to establish that one TNF inhibitor is superior – only that patients can sometimes succeed with one and fail another.
“As far as which biologic to initiate, my personal opinion is I don’t care, and I tell the patients that I don’t mind if the insurer picks out of this category because I’m flipping a coin as well,” she said.
Step mandates become objectionable, Dr. Kolba said, when they are purportedly based in science that doesn’t exist, or when they seem to exist only to wear down the provider.
“With private insurance not only do they have the drug of the year, they’re going to make me battle for every single prescription. When I say I have tried this patient on maximal tolerable doses of all these DMARDs, they ought to believe me. Yet I get six-page forms back saying, ‘Give me the start and stop dates of all the drugs you’ve used.’”
States constrain fail first
For many specialists treating patients with biologics, some of these hurdles are already getting lowered.
Concerns about physician choice, a lack of transparency in insurer decision making, and the ethics of forcing patients to fail have led advocacy groups to press hard in recent years for legislation limiting step therapy – with successes in a dozen states.
While the state legislation is not disease or drug specific, it has important implications for clinicians treating with biologics. “Step therapy in its genesis was a good idea – it’s OK to try to reduce costs in the health care system,” said Patrick Stone, state government relations manager at the National Psoriasis Foundation in Annapolis, Md., a group that works extensively on step therapy issues. “But when these protocols were first crafted, medications like biologics weren’t in use.”
Jeff Okazaki, associate director of the Coalition of State Rheumatology Organizations, a group based in Schaumberg, Ill., said lawmakers are starting to accept that in terms of cost of care, “somebody not being treated appropriately and down the line has organ damage or comorbidity because of incorrect treatment decisions due to step therapy is a higher burden.”
Moreover, he said, “we’d seen protocols requiring five or more steps, and for each step you have to try it at least 90 days.” For a patient with rheumatic or autoimmune disease, “getting through something like that can just be devastating.”
In 2011, Connecticut, Mississippi, and Arkansas became the first states to pass legislation limiting some aspect of step therapy. Since then, nine additional states have passed legislation varying in focus and scope.
In Kentucky, for example, patients cannot be forced by their insurer to remain on an ineffective therapy for more than 30 days, and insurers must respond to physician requests for an override within 2 days. Mississippi allows physicians to override insurer decisions with proof of clinical evidence. In California, legislation passed last year aims to reduce bureaucracy and speed up response to physician requests for overrides.
Mr. Stone and Mr. Okazaki are working in a coalition with other dermatology, rheumatology, and GI groups to push bills in seven more states, including New York, North Carolina, and Ohio.
While all the bills differ in what they attempt to limit, the model legislation has three basic objectives, Mr. Okazaki said. “We want a clear set of clinical guidelines, a quick review process, and overrides that allow for exceptions in cases where patients shouldn’t have to go through step therapy.”
Clinical strategies and research gaps
New legislation undoubtedly will help providers and patients get access to their choice of treatment agents. But so long as biologics are expensive – and it will be a while before the first biosimilar drugs, which will have efficacy and safety similar to their reference biologics, reduce prices in any meaningful way – step therapy will likely remain the norm.
One of the key difficulties providers face when pushing back on an insurer in favor of a biologic drug is insufficient clinical evidence.
With IBD, Dr. Rubin said, “we need a need more longitudinal understanding” and better prognostic indicators “in order to justify spending the extra money or going to one of these therapies.”
Dr. Hanauer said one of the limitations he faces in practice is insufficient clinical evidence for biologics early in the treatment pathway for IBD.
RA “is much more common than Crohn’s disease is. In trials, it’s much easier to recruit hundreds of patients [for an RA trial], while with Crohn’s it’s very hard to enroll more than a couple a year at most sites,” he said. “And as you move earlier in the treatment pathway that becomes somewhat more difficult as well.”
His solution for now, he said, is to follow established step pathways in an accelerated way, for “a rapid transition toward highly effective therapies” without having to face extensive pushback from insurers.
“The idea is to initiate immunosuppressants for any patients with sufficient disease activity to justify steroids,” Dr. Hanauer said. “Their steroids are then tapered, and while on immunosuppressants, patients are in a perfect setup to get combination therapy with an immunosuppressive and a biologic – and that’s a 2- to 3-month transition, not 2-3 years.”
Dr. Kolba said that despite the wide array of options for treating RA, the specialty suffers from a dearth of understanding as to why some patients fail drugs while others succeed, even within the same drug class.
Rheumatologists’ prescribing choices would be highly influenced by better biomarkers, were they to become available, she said. And they’d have far better arguments when confronted with payer pushback.
“We’re all looking for that magic biologic marker to tell me which drug to use,” Dr. Kolba said, “because God knows if I had a blood test that said ‘this is the drug,’ I would go to the mat with the insurer.”
Men seen as main source of TB transmission
More than half of tuberculosis infections among men, women, and children were seen to derive from contacts with adult men, according to findings from research teams working in the United Kingdom, Zambia, and South Africa.
Understanding TB infection incidence by age and sex of source cases, and where and how often contacts occur, is critical to controlling transmission and directing prevention and treatment efforts. For this study, published online in the American Journal of Epidemiology (Am J Epidemiol. 2015 Dec 8. doi: 10.1093/aje/kwv160), researchers compared TB prevalence data in adults from a recent study in South Africa and Zambia and from an earlier, related study in children with data on daily contact patterns gathered through interviews with more than 3,500 adults 18 and older (53% female).
Close contacts were defined as face-to-face conversations, while casual contacts were defined as sharing indoor space, a potentially important source of TB transmission. In the interviews, adults reported an average of 4.9 close contacts and 10.4 casual contacts daily. They also reported the age groups and sexes with which their contacts occurred.
The authors of the study, led by Dr. Peter J. Dodd of the University of Sheffield (U.K.), said the finding on adult males as the likely drivers of TB transmission in both genders was surprising, because the study also revealed that daily close contacts occurred preferentially among age groups and among members of the same sex.
More than 63% of women’s close contacts and 61% of men’s were among members of the same sex. Adults averaged 0.8 close contacts per day with children under 12, though women had a slightly higher rate of contact than men. Among adults, estimated infections from contact with adult men was 57.3% in South Africa and 65.7% in Zambia. Estimated transmission from contact with men was 50% or higher in all age groups, in both sexes, and in both countries, except in girls 12 and younger and boys 4 and younger in South Africa.
“We noticed in the study that there was preferential mixing by gender,” Dr. Dodd said in an interview. “If there was the same amount of TB in men and women, you’d have expected women to be responsible for the majority of transmission to women and vice versa. But in fact there’s so much more TB in men, that they’re still responsible for the majority of transmission in women.”
Young children’s high proportion of TB infection attributable to contact with men was surprising, they noted, because their contact rates with women were higher. This suggests “that even in this age group, the higher prevalence in males tended to outweigh the higher contact rates between young children and women,” the researchers wrote in their analysis.
Prevalence of TB was markedly higher in men than women (0.9% vs. 0.4% in Zambia, and 3% vs. 2% in South Africa). While the reasons for more TB in men are not well understood, these likely include both biological and social factors, including time before seeking care, and access to care. If men are slower to report or get diagnosed, because of work or other considerations, they will have higher prevalence of infectious TB disease, Dr. Dodd said. Preferential mixing by gender means that men are also more likely to be exposed to infectious TB by other men.
The study also found that incidence of infection was between 1.5 and 6 times higher in adults than was measured in children. “Adults are likely to have higher rates of exposure to TB, because adults on average have more contact with other adults than they do with children – and it’s the adults who tend to have infectious TB disease,” Dr. Dodd said.
Tuberculosis infection incidence based on surveys in children might underestimate true incidence in adults in TB-endemic settings, the researchers cautioned in their analysis.
“For hyperendemic communities in South Africa, which may have an incidence of M. tuberculosis infection in children as high as 4% per year, our findings imply that incidence rates in never-infected adults may be as high as 10% per year, rates which have rarely been seen outside institutional settings.”
Care and control of tuberculosis in males, the researchers concluded, “is critical to protecting men, women, and children from tuberculosis.”
Individual researchers were funded by the Bill and Melinda Gates Foundation, the Medical Research Council (U.K.), and the Wellcome Trust. None of the researchers reported conflicts of interest.
More than half of tuberculosis infections among men, women, and children were seen to derive from contacts with adult men, according to findings from research teams working in the United Kingdom, Zambia, and South Africa.
Understanding TB infection incidence by age and sex of source cases, and where and how often contacts occur, is critical to controlling transmission and directing prevention and treatment efforts. For this study, published online in the American Journal of Epidemiology (Am J Epidemiol. 2015 Dec 8. doi: 10.1093/aje/kwv160), researchers compared TB prevalence data in adults from a recent study in South Africa and Zambia and from an earlier, related study in children with data on daily contact patterns gathered through interviews with more than 3,500 adults 18 and older (53% female).
Close contacts were defined as face-to-face conversations, while casual contacts were defined as sharing indoor space, a potentially important source of TB transmission. In the interviews, adults reported an average of 4.9 close contacts and 10.4 casual contacts daily. They also reported the age groups and sexes with which their contacts occurred.
The authors of the study, led by Dr. Peter J. Dodd of the University of Sheffield (U.K.), said the finding on adult males as the likely drivers of TB transmission in both genders was surprising, because the study also revealed that daily close contacts occurred preferentially among age groups and among members of the same sex.
More than 63% of women’s close contacts and 61% of men’s were among members of the same sex. Adults averaged 0.8 close contacts per day with children under 12, though women had a slightly higher rate of contact than men. Among adults, estimated infections from contact with adult men was 57.3% in South Africa and 65.7% in Zambia. Estimated transmission from contact with men was 50% or higher in all age groups, in both sexes, and in both countries, except in girls 12 and younger and boys 4 and younger in South Africa.
“We noticed in the study that there was preferential mixing by gender,” Dr. Dodd said in an interview. “If there was the same amount of TB in men and women, you’d have expected women to be responsible for the majority of transmission to women and vice versa. But in fact there’s so much more TB in men, that they’re still responsible for the majority of transmission in women.”
Young children’s high proportion of TB infection attributable to contact with men was surprising, they noted, because their contact rates with women were higher. This suggests “that even in this age group, the higher prevalence in males tended to outweigh the higher contact rates between young children and women,” the researchers wrote in their analysis.
Prevalence of TB was markedly higher in men than women (0.9% vs. 0.4% in Zambia, and 3% vs. 2% in South Africa). While the reasons for more TB in men are not well understood, these likely include both biological and social factors, including time before seeking care, and access to care. If men are slower to report or get diagnosed, because of work or other considerations, they will have higher prevalence of infectious TB disease, Dr. Dodd said. Preferential mixing by gender means that men are also more likely to be exposed to infectious TB by other men.
The study also found that incidence of infection was between 1.5 and 6 times higher in adults than was measured in children. “Adults are likely to have higher rates of exposure to TB, because adults on average have more contact with other adults than they do with children – and it’s the adults who tend to have infectious TB disease,” Dr. Dodd said.
Tuberculosis infection incidence based on surveys in children might underestimate true incidence in adults in TB-endemic settings, the researchers cautioned in their analysis.
“For hyperendemic communities in South Africa, which may have an incidence of M. tuberculosis infection in children as high as 4% per year, our findings imply that incidence rates in never-infected adults may be as high as 10% per year, rates which have rarely been seen outside institutional settings.”
Care and control of tuberculosis in males, the researchers concluded, “is critical to protecting men, women, and children from tuberculosis.”
Individual researchers were funded by the Bill and Melinda Gates Foundation, the Medical Research Council (U.K.), and the Wellcome Trust. None of the researchers reported conflicts of interest.
More than half of tuberculosis infections among men, women, and children were seen to derive from contacts with adult men, according to findings from research teams working in the United Kingdom, Zambia, and South Africa.
Understanding TB infection incidence by age and sex of source cases, and where and how often contacts occur, is critical to controlling transmission and directing prevention and treatment efforts. For this study, published online in the American Journal of Epidemiology (Am J Epidemiol. 2015 Dec 8. doi: 10.1093/aje/kwv160), researchers compared TB prevalence data in adults from a recent study in South Africa and Zambia and from an earlier, related study in children with data on daily contact patterns gathered through interviews with more than 3,500 adults 18 and older (53% female).
Close contacts were defined as face-to-face conversations, while casual contacts were defined as sharing indoor space, a potentially important source of TB transmission. In the interviews, adults reported an average of 4.9 close contacts and 10.4 casual contacts daily. They also reported the age groups and sexes with which their contacts occurred.
The authors of the study, led by Dr. Peter J. Dodd of the University of Sheffield (U.K.), said the finding on adult males as the likely drivers of TB transmission in both genders was surprising, because the study also revealed that daily close contacts occurred preferentially among age groups and among members of the same sex.
More than 63% of women’s close contacts and 61% of men’s were among members of the same sex. Adults averaged 0.8 close contacts per day with children under 12, though women had a slightly higher rate of contact than men. Among adults, estimated infections from contact with adult men was 57.3% in South Africa and 65.7% in Zambia. Estimated transmission from contact with men was 50% or higher in all age groups, in both sexes, and in both countries, except in girls 12 and younger and boys 4 and younger in South Africa.
“We noticed in the study that there was preferential mixing by gender,” Dr. Dodd said in an interview. “If there was the same amount of TB in men and women, you’d have expected women to be responsible for the majority of transmission to women and vice versa. But in fact there’s so much more TB in men, that they’re still responsible for the majority of transmission in women.”
Young children’s high proportion of TB infection attributable to contact with men was surprising, they noted, because their contact rates with women were higher. This suggests “that even in this age group, the higher prevalence in males tended to outweigh the higher contact rates between young children and women,” the researchers wrote in their analysis.
Prevalence of TB was markedly higher in men than women (0.9% vs. 0.4% in Zambia, and 3% vs. 2% in South Africa). While the reasons for more TB in men are not well understood, these likely include both biological and social factors, including time before seeking care, and access to care. If men are slower to report or get diagnosed, because of work or other considerations, they will have higher prevalence of infectious TB disease, Dr. Dodd said. Preferential mixing by gender means that men are also more likely to be exposed to infectious TB by other men.
The study also found that incidence of infection was between 1.5 and 6 times higher in adults than was measured in children. “Adults are likely to have higher rates of exposure to TB, because adults on average have more contact with other adults than they do with children – and it’s the adults who tend to have infectious TB disease,” Dr. Dodd said.
Tuberculosis infection incidence based on surveys in children might underestimate true incidence in adults in TB-endemic settings, the researchers cautioned in their analysis.
“For hyperendemic communities in South Africa, which may have an incidence of M. tuberculosis infection in children as high as 4% per year, our findings imply that incidence rates in never-infected adults may be as high as 10% per year, rates which have rarely been seen outside institutional settings.”
Care and control of tuberculosis in males, the researchers concluded, “is critical to protecting men, women, and children from tuberculosis.”
Individual researchers were funded by the Bill and Melinda Gates Foundation, the Medical Research Council (U.K.), and the Wellcome Trust. None of the researchers reported conflicts of interest.
FROM THE AMERICAN JOURNAL OF EPIDEMIOLOGY
Key clinical point: More than half of TB infections among men, women, and children were attributable to contact with adult men in 2 African cohorts.
Major finding: Estimated overall adult infections attributable to contact with adult men was 57.3% in South Africa and 65.7% in Zambia, and more than 50% overall for all ages including children, with estimated incidence in adults 1.5-6 times higher than that in children.
Data source: Interviews with 3,528 adults on daily close and casual contacts conducted in 24 South African and Zambian communities in 2011, compared with recent empirical incidence data by age group and sex for the same regions.
Disclosures: Individual researchers were funded by the Bill and Melinda Gates Foundation, the Medical Research Council (U.K.), and the Wellcome Trust. None reported conflicts of interest.
Minority of U.S. hospitals mandate flu vaccination
Less than 50% of U.S. hospitals require health care workers to receive annual flu shots, according to a survey study with responses from nearly 500 facilities.
The study, published online in Infection Control & Hospital Epidemiology (2015 Nov 27. doi: 10.1017/ice.2015.277), also found that only 1.3% of U.S. Veterans Affairs hospitals mandate flu shots, despite no law preventing them from doing so.
Dr. M. Todd Greene of the University of Michigan, Ann Arbor, and the Veterans Affairs/University of Michigan Patient Safety Enhancement Program, led the study, which asked hospital infection specialists to report on their institutions’ policies regarding annual vaccines, the stated reasons behind these policies, and other efforts to promote vaccination or discourage nonvaccination in 2013. Only 42.7% of respondents from 386 non-VA hospitals said their institutions required universal vaccination of personnel. However, many reported policies promoting uptake and/or mandating declination forms and face masks for personnel who opted out.
Among non-VA hospitals without mandatory vaccination, 22% said their administrations were unwilling to require it, while another 22% said vaccination was “strongly recommended” or otherwise promoted, and 21% said face masks and signed declination forms were mandatory for nonvaccinated personnel. Union concerns were cited by 8% as a reason vaccination was not required. In the VA system, meanwhile, 57% of hospitals without mandatory vaccination cited federal agency status as a reason, and more than a quarter cited union issues.
Dr. Greene and colleagues noted that while the VA does not have a national vaccination requirement, individual hospitals are free to determine their own policies. The Veterans Hospital Administration estimates vaccine uptake among workers at its hospitals to be only 55% in recent flu seasons, while a recent study by the Centers for Disease Control and Prevention found that overall about 77% of U.S. health care workers in diverse clinical settings received flu shots in 2014-2015, and that those settings with vaccination requirements saw 96% of personnel covered.
Dr. Greene and colleagues’ study was funded by the Blue Cross Blue Shield of Michigan Foundation, the Department of Veterans Affairs, and the National Center for Patient Safety. None of its authors disclosed conflicts of interest.
Less than 50% of U.S. hospitals require health care workers to receive annual flu shots, according to a survey study with responses from nearly 500 facilities.
The study, published online in Infection Control & Hospital Epidemiology (2015 Nov 27. doi: 10.1017/ice.2015.277), also found that only 1.3% of U.S. Veterans Affairs hospitals mandate flu shots, despite no law preventing them from doing so.
Dr. M. Todd Greene of the University of Michigan, Ann Arbor, and the Veterans Affairs/University of Michigan Patient Safety Enhancement Program, led the study, which asked hospital infection specialists to report on their institutions’ policies regarding annual vaccines, the stated reasons behind these policies, and other efforts to promote vaccination or discourage nonvaccination in 2013. Only 42.7% of respondents from 386 non-VA hospitals said their institutions required universal vaccination of personnel. However, many reported policies promoting uptake and/or mandating declination forms and face masks for personnel who opted out.
Among non-VA hospitals without mandatory vaccination, 22% said their administrations were unwilling to require it, while another 22% said vaccination was “strongly recommended” or otherwise promoted, and 21% said face masks and signed declination forms were mandatory for nonvaccinated personnel. Union concerns were cited by 8% as a reason vaccination was not required. In the VA system, meanwhile, 57% of hospitals without mandatory vaccination cited federal agency status as a reason, and more than a quarter cited union issues.
Dr. Greene and colleagues noted that while the VA does not have a national vaccination requirement, individual hospitals are free to determine their own policies. The Veterans Hospital Administration estimates vaccine uptake among workers at its hospitals to be only 55% in recent flu seasons, while a recent study by the Centers for Disease Control and Prevention found that overall about 77% of U.S. health care workers in diverse clinical settings received flu shots in 2014-2015, and that those settings with vaccination requirements saw 96% of personnel covered.
Dr. Greene and colleagues’ study was funded by the Blue Cross Blue Shield of Michigan Foundation, the Department of Veterans Affairs, and the National Center for Patient Safety. None of its authors disclosed conflicts of interest.
Less than 50% of U.S. hospitals require health care workers to receive annual flu shots, according to a survey study with responses from nearly 500 facilities.
The study, published online in Infection Control & Hospital Epidemiology (2015 Nov 27. doi: 10.1017/ice.2015.277), also found that only 1.3% of U.S. Veterans Affairs hospitals mandate flu shots, despite no law preventing them from doing so.
Dr. M. Todd Greene of the University of Michigan, Ann Arbor, and the Veterans Affairs/University of Michigan Patient Safety Enhancement Program, led the study, which asked hospital infection specialists to report on their institutions’ policies regarding annual vaccines, the stated reasons behind these policies, and other efforts to promote vaccination or discourage nonvaccination in 2013. Only 42.7% of respondents from 386 non-VA hospitals said their institutions required universal vaccination of personnel. However, many reported policies promoting uptake and/or mandating declination forms and face masks for personnel who opted out.
Among non-VA hospitals without mandatory vaccination, 22% said their administrations were unwilling to require it, while another 22% said vaccination was “strongly recommended” or otherwise promoted, and 21% said face masks and signed declination forms were mandatory for nonvaccinated personnel. Union concerns were cited by 8% as a reason vaccination was not required. In the VA system, meanwhile, 57% of hospitals without mandatory vaccination cited federal agency status as a reason, and more than a quarter cited union issues.
Dr. Greene and colleagues noted that while the VA does not have a national vaccination requirement, individual hospitals are free to determine their own policies. The Veterans Hospital Administration estimates vaccine uptake among workers at its hospitals to be only 55% in recent flu seasons, while a recent study by the Centers for Disease Control and Prevention found that overall about 77% of U.S. health care workers in diverse clinical settings received flu shots in 2014-2015, and that those settings with vaccination requirements saw 96% of personnel covered.
Dr. Greene and colleagues’ study was funded by the Blue Cross Blue Shield of Michigan Foundation, the Department of Veterans Affairs, and the National Center for Patient Safety. None of its authors disclosed conflicts of interest.
FROM INFECTION CONTROL & HOSPITAL EPIDEMIOLOGY
Key clinical point: Despite evidence that mandatory influenza vaccination policies result in high coverage, fewer than half of U.S. hospitals, and very few VA hospitals, require workers to be vaccinated.
Major finding: 42.7% of non-VA hospitals and only 1.3% of VA hospitals required all health care workers to receive flu shots in 2013.
Data source: A survey of infection control specialists at 571 non-VA hospitals (71% responding, n = 403) and 126 VA hospitals (63% responding, n = 80) in 2013.
Disclosures: Blue Cross Blue Shield of Michigan Foundation, the Department of Veterans Affairs, and the National Center for Patient Safety funded the study, and authors reported no conflicts of interest.
Chagas disease: Neither foreign nor untreatable
Chagas disease is a vector-borne parasitic disease, endemic to the Americas, that remains as little recognized by U.S. patients and practitioners as the obscure winged insects that transmit it.
Transmission occurs when triatomine bugs, commonly called “kissing bugs,” pierce the skin to feed and leave behind parasite-infected feces that can enter the bloodstream; pregnant women can also transmit Chagas to their newborns.
About a third of patients infected with Trypanosoma cruzi, the protozoan parasite that causes Chagas, will develop cardiac abnormalities such as cardiomyopathy, arrhythmias, and heart failure – often decades after becoming infected. In the United States, where blood banks began screening for Chagas in 2007, patients without symptoms are likely to learn they are positive only after donating blood.
Conventional wisdom has long maintained that Chagas is limited to Central and South America. But immigration from Chagas-endemic countries, such as El Salvador, Mexico, and Bolivia, means more people are living with the disease in the United States.
“One percent of the Latin American immigrant population we screen [in Los Angeles] has Chagas,” said Dr. Sheba K. Meymandi, cardiologist and director of Center of Excellence for Chagas Disease at Olive View–UCLA Medical Center in Los Angeles, who also works with the city’s health department to detect Chagas. “That’s huge.”
Meanwhile, blood banks are discovering more cases among people without ties to Latin America, and species of kissing bugs native to the southern United States are increasingly recognized as a non-negligible source of Chagas transmission. Of 39 Chagas cases reported to Texas health authorities in 2013 and 2014, 12 were thought to be locally acquired.
Dr. Heather Yun, an infectious disease specialist at the San Antonio Military Medical Center, said risk factors for local transmission are not well established, but “we think people who are living in poverty in substandard housing, people who spend a lot of time outdoors, especially at night, and people involved with direct blood contact with wild game in Southern parts of the United States” may be at higher risk.
A U.S. disease
Evidence is amassing quickly that Chagas is a U.S. disease. But U.S. clinicians still lag in their knowledge of it, say physicians treating Chagas cases. “In medical school we get a 2-hour lecture on it, and it’s always been presented as an exotic disease and one you don’t treat,” Dr. Meymandi said.
The persistent perception of Chagas as a foreign disease means clinicians are inclined to dismiss positive results from a blood screening, particularly from someone who is not from Latin America. Yet cardiologists, ID practitioners, obstetricians, and primary care physicians all need to be aware that cases do occur in the United States and are potentially treatable.
Dr. Laila Woc-Colburn, an infectious disease and tropical medicine specialist at Baylor College of Medicine in Houston, said many people with Chagas never make it to an infectious disease specialist or cardiologist for a work-up. “When you test positive on serology [after a blood donation], you get a letter recommending you consult your physician. Most will go to their primary care doctors, who might say ‘this isn’t a disease in the United States.’ In Houston, that is often the case.”
Dr. Meymandi, who has treated hundreds of patients with Chagas with and without cardiac involvement, said any physician with a potential Chagas case must act. “If you get someone that’s positive, it’s your duty as a physician to confirm the positivity with CDC,” she said.
Dr. Yun concurred. “The most important message is, do something,” she said. “Don’t just assume it’s a false positive.”
Diagnosis is not simple and requires testing beyond the initial ELISA assay used in blood-bank screening. Confirmatory tests must be carried out in coordination with the Centers for Disease Control and Prevention. Also, with no agents approved by the Food and Drug Administration to treat Chagas, treatment is available only through the CDC’s investigational drugs protocol. Both drugs used in Chagas, benznidazole and nifurtimox, come with serious adverse effects that must be closely monitored.
“It’s time consuming, filling out the forms, getting the consent, tracking and sending back lab results to CDC in order to get drugs – it’s not like you can just write a prescription,” Dr. Meymandi said. But, “if you don’t know how to treat the patient or don’t have time, find someone like me,” she noted, adding that she is available to counsel any physician daunted by a potential Chagas case.
Treatment options
No formal clinical algorithm exists for Chagas, but Dr. Meymandi, Dr. Yun, and Dr. Woc-Colburn all pointed to a 2007 JAMA article, which describes diagnosis and treatment protocols, as an important reference for clinicians to start with. It’s “the best approximation of a clinical guideline we have,” Dr. Yun said (JAMA. 2007;298[18]:2171-81. doi:10.1001/jama.298.18.2171).
Dr. Meymandi, who has treated more Chagas patients than has any other U.S. clinician, said that treatment has changed somewhat since the JAMA article was published. In 2007, she said, nifurtimox was the main drug available through CDC, while benznidazole, which is somewhat better tolerated and has shorter treatment duration, has since become the first-line agent.
“We’ve lowered the dose of benznidazole, maxing out at 400 mg/day to decrease the toxicity,” she said. Also, treatment is now being extended to some patients aged 60 years and older.
The decision to treat or not treat, clinicians say, depends on the patient’s age, disease progression, comorbidities and potential serious drug interactions, and willingness to tolerate side effects that, with nifurtimox especially, can include skin sloughing, rash, and psychological and neurologic symptoms including depression and peripheral neuropathy.
“If you don’t have side effects, you’re not taking the drugs,” Dr. Meymandi said. Dr. Woc-Colburn noted that polypharmacy was a major consideration when treating older adults for Chagas. “If I have a patient who has diabetes, obesity, [and] end-stage renal disease, it’s not going to be ideal to give [benznidazole].”
Recent, highly anticipated results from BENEFIT, a large randomized trial (n = 2,854) showed that benznidazole reduced parasite load but was not helpful in halting cardiac damage at 5 years’ follow-up in patients with established Chagas cardiomyopathy (N Engl J Med. 2015 Oct;373:1295-306. doi:10.1056/NEJMoa1507574).
Dr. Meymandi, whose earlier research established that Chagas cardiomyopathy carries significantly higher morbidity and mortality than does non–Chagas cardiomyopathy (Circulation. 2012;126:A18171), said that the BENEFIT results underscore the need for physicians to be bullish in their approach to treating Chagas soon after diagnosis.
“It doesn’t matter if they’re symptomatic or asymptomatic. You can’t wait till they progress to treat. If you wait for the progression of disease you’ve lost the battle. You can’t wait and follow conservatively until you see the complications, because once those complications have started the parasitic load is too high for you to have an impact,” she said.
Dr. Yun said that given the toxicity of current treatment, she hoped to see more studies show clearer evidence of clinical benefit, “either reductions in mortality or reductions in end organ disease.” Most studies “have focused on clearance of parasite, which is important, but it’s not as important decreasing the risk of death or cardiomyopathy or heart failure.”
Rick Tarleton, Ph.D., a biologist the University of Georgia, in Athens, who has worked on Chagas for more than 30 years, said that because Chagas pathology is directly tied to parasite load – and not, as people have suggested in the past, an autoimmune reaction resulting from parasite exposure – drug treatment may prove to be worthwhile even in patients with significant cardiac involvement.
“You get rid of the parasite, you get rid of the progression of the disease,” Dr. Tarleton said. Even the findings from the BENEFIT trial, he said, did not lead him to conclude that treatment in people with established cardiac disease was futile.
“If you’re treating people who are already chronically infected and showing symptoms, the question is not have you reversed the damage, it’s have you stopped accumulating damage,” he noted. “And a 5-year follow-up is probably not long enough to know whether you’ve stopped accumulating.”
“We have drugs, they’re not great, they do have side effects, they don’t always work,” Dr. Tarleton said. “But they’re better than nothing. And they ought to be more widely used.”
Dr. Meymandi said that current supplies of benznidazole at CDC are low and that a dozen patients at her clinic are awaiting treatment. Meanwhile, access may soon be complicated further by the announcement, this month, that KaloBios Pharmaceuticals had bought the rights to seek FDA approval of benznidazole and market it in the United States.
The same company’s CEO came under fire in recent months for acquiring rights to an inexpensive drug to treat toxoplasmosis in AIDS patients, then announcing a price increase from $13.50 to $750 a pill.
“Everyone’s really concerned,” Dr. Meymandi said, “because Chagas is a disease of the poor.”
Chagas disease is a vector-borne parasitic disease, endemic to the Americas, that remains as little recognized by U.S. patients and practitioners as the obscure winged insects that transmit it.
Transmission occurs when triatomine bugs, commonly called “kissing bugs,” pierce the skin to feed and leave behind parasite-infected feces that can enter the bloodstream; pregnant women can also transmit Chagas to their newborns.
About a third of patients infected with Trypanosoma cruzi, the protozoan parasite that causes Chagas, will develop cardiac abnormalities such as cardiomyopathy, arrhythmias, and heart failure – often decades after becoming infected. In the United States, where blood banks began screening for Chagas in 2007, patients without symptoms are likely to learn they are positive only after donating blood.
Conventional wisdom has long maintained that Chagas is limited to Central and South America. But immigration from Chagas-endemic countries, such as El Salvador, Mexico, and Bolivia, means more people are living with the disease in the United States.
“One percent of the Latin American immigrant population we screen [in Los Angeles] has Chagas,” said Dr. Sheba K. Meymandi, cardiologist and director of Center of Excellence for Chagas Disease at Olive View–UCLA Medical Center in Los Angeles, who also works with the city’s health department to detect Chagas. “That’s huge.”
Meanwhile, blood banks are discovering more cases among people without ties to Latin America, and species of kissing bugs native to the southern United States are increasingly recognized as a non-negligible source of Chagas transmission. Of 39 Chagas cases reported to Texas health authorities in 2013 and 2014, 12 were thought to be locally acquired.
Dr. Heather Yun, an infectious disease specialist at the San Antonio Military Medical Center, said risk factors for local transmission are not well established, but “we think people who are living in poverty in substandard housing, people who spend a lot of time outdoors, especially at night, and people involved with direct blood contact with wild game in Southern parts of the United States” may be at higher risk.
A U.S. disease
Evidence is amassing quickly that Chagas is a U.S. disease. But U.S. clinicians still lag in their knowledge of it, say physicians treating Chagas cases. “In medical school we get a 2-hour lecture on it, and it’s always been presented as an exotic disease and one you don’t treat,” Dr. Meymandi said.
The persistent perception of Chagas as a foreign disease means clinicians are inclined to dismiss positive results from a blood screening, particularly from someone who is not from Latin America. Yet cardiologists, ID practitioners, obstetricians, and primary care physicians all need to be aware that cases do occur in the United States and are potentially treatable.
Dr. Laila Woc-Colburn, an infectious disease and tropical medicine specialist at Baylor College of Medicine in Houston, said many people with Chagas never make it to an infectious disease specialist or cardiologist for a work-up. “When you test positive on serology [after a blood donation], you get a letter recommending you consult your physician. Most will go to their primary care doctors, who might say ‘this isn’t a disease in the United States.’ In Houston, that is often the case.”
Dr. Meymandi, who has treated hundreds of patients with Chagas with and without cardiac involvement, said any physician with a potential Chagas case must act. “If you get someone that’s positive, it’s your duty as a physician to confirm the positivity with CDC,” she said.
Dr. Yun concurred. “The most important message is, do something,” she said. “Don’t just assume it’s a false positive.”
Diagnosis is not simple and requires testing beyond the initial ELISA assay used in blood-bank screening. Confirmatory tests must be carried out in coordination with the Centers for Disease Control and Prevention. Also, with no agents approved by the Food and Drug Administration to treat Chagas, treatment is available only through the CDC’s investigational drugs protocol. Both drugs used in Chagas, benznidazole and nifurtimox, come with serious adverse effects that must be closely monitored.
“It’s time consuming, filling out the forms, getting the consent, tracking and sending back lab results to CDC in order to get drugs – it’s not like you can just write a prescription,” Dr. Meymandi said. But, “if you don’t know how to treat the patient or don’t have time, find someone like me,” she noted, adding that she is available to counsel any physician daunted by a potential Chagas case.
Treatment options
No formal clinical algorithm exists for Chagas, but Dr. Meymandi, Dr. Yun, and Dr. Woc-Colburn all pointed to a 2007 JAMA article, which describes diagnosis and treatment protocols, as an important reference for clinicians to start with. It’s “the best approximation of a clinical guideline we have,” Dr. Yun said (JAMA. 2007;298[18]:2171-81. doi:10.1001/jama.298.18.2171).
Dr. Meymandi, who has treated more Chagas patients than has any other U.S. clinician, said that treatment has changed somewhat since the JAMA article was published. In 2007, she said, nifurtimox was the main drug available through CDC, while benznidazole, which is somewhat better tolerated and has shorter treatment duration, has since become the first-line agent.
“We’ve lowered the dose of benznidazole, maxing out at 400 mg/day to decrease the toxicity,” she said. Also, treatment is now being extended to some patients aged 60 years and older.
The decision to treat or not treat, clinicians say, depends on the patient’s age, disease progression, comorbidities and potential serious drug interactions, and willingness to tolerate side effects that, with nifurtimox especially, can include skin sloughing, rash, and psychological and neurologic symptoms including depression and peripheral neuropathy.
“If you don’t have side effects, you’re not taking the drugs,” Dr. Meymandi said. Dr. Woc-Colburn noted that polypharmacy was a major consideration when treating older adults for Chagas. “If I have a patient who has diabetes, obesity, [and] end-stage renal disease, it’s not going to be ideal to give [benznidazole].”
Recent, highly anticipated results from BENEFIT, a large randomized trial (n = 2,854) showed that benznidazole reduced parasite load but was not helpful in halting cardiac damage at 5 years’ follow-up in patients with established Chagas cardiomyopathy (N Engl J Med. 2015 Oct;373:1295-306. doi:10.1056/NEJMoa1507574).
Dr. Meymandi, whose earlier research established that Chagas cardiomyopathy carries significantly higher morbidity and mortality than does non–Chagas cardiomyopathy (Circulation. 2012;126:A18171), said that the BENEFIT results underscore the need for physicians to be bullish in their approach to treating Chagas soon after diagnosis.
“It doesn’t matter if they’re symptomatic or asymptomatic. You can’t wait till they progress to treat. If you wait for the progression of disease you’ve lost the battle. You can’t wait and follow conservatively until you see the complications, because once those complications have started the parasitic load is too high for you to have an impact,” she said.
Dr. Yun said that given the toxicity of current treatment, she hoped to see more studies show clearer evidence of clinical benefit, “either reductions in mortality or reductions in end organ disease.” Most studies “have focused on clearance of parasite, which is important, but it’s not as important decreasing the risk of death or cardiomyopathy or heart failure.”
Rick Tarleton, Ph.D., a biologist the University of Georgia, in Athens, who has worked on Chagas for more than 30 years, said that because Chagas pathology is directly tied to parasite load – and not, as people have suggested in the past, an autoimmune reaction resulting from parasite exposure – drug treatment may prove to be worthwhile even in patients with significant cardiac involvement.
“You get rid of the parasite, you get rid of the progression of the disease,” Dr. Tarleton said. Even the findings from the BENEFIT trial, he said, did not lead him to conclude that treatment in people with established cardiac disease was futile.
“If you’re treating people who are already chronically infected and showing symptoms, the question is not have you reversed the damage, it’s have you stopped accumulating damage,” he noted. “And a 5-year follow-up is probably not long enough to know whether you’ve stopped accumulating.”
“We have drugs, they’re not great, they do have side effects, they don’t always work,” Dr. Tarleton said. “But they’re better than nothing. And they ought to be more widely used.”
Dr. Meymandi said that current supplies of benznidazole at CDC are low and that a dozen patients at her clinic are awaiting treatment. Meanwhile, access may soon be complicated further by the announcement, this month, that KaloBios Pharmaceuticals had bought the rights to seek FDA approval of benznidazole and market it in the United States.
The same company’s CEO came under fire in recent months for acquiring rights to an inexpensive drug to treat toxoplasmosis in AIDS patients, then announcing a price increase from $13.50 to $750 a pill.
“Everyone’s really concerned,” Dr. Meymandi said, “because Chagas is a disease of the poor.”
Chagas disease is a vector-borne parasitic disease, endemic to the Americas, that remains as little recognized by U.S. patients and practitioners as the obscure winged insects that transmit it.
Transmission occurs when triatomine bugs, commonly called “kissing bugs,” pierce the skin to feed and leave behind parasite-infected feces that can enter the bloodstream; pregnant women can also transmit Chagas to their newborns.
About a third of patients infected with Trypanosoma cruzi, the protozoan parasite that causes Chagas, will develop cardiac abnormalities such as cardiomyopathy, arrhythmias, and heart failure – often decades after becoming infected. In the United States, where blood banks began screening for Chagas in 2007, patients without symptoms are likely to learn they are positive only after donating blood.
Conventional wisdom has long maintained that Chagas is limited to Central and South America. But immigration from Chagas-endemic countries, such as El Salvador, Mexico, and Bolivia, means more people are living with the disease in the United States.
“One percent of the Latin American immigrant population we screen [in Los Angeles] has Chagas,” said Dr. Sheba K. Meymandi, cardiologist and director of Center of Excellence for Chagas Disease at Olive View–UCLA Medical Center in Los Angeles, who also works with the city’s health department to detect Chagas. “That’s huge.”
Meanwhile, blood banks are discovering more cases among people without ties to Latin America, and species of kissing bugs native to the southern United States are increasingly recognized as a non-negligible source of Chagas transmission. Of 39 Chagas cases reported to Texas health authorities in 2013 and 2014, 12 were thought to be locally acquired.
Dr. Heather Yun, an infectious disease specialist at the San Antonio Military Medical Center, said risk factors for local transmission are not well established, but “we think people who are living in poverty in substandard housing, people who spend a lot of time outdoors, especially at night, and people involved with direct blood contact with wild game in Southern parts of the United States” may be at higher risk.
A U.S. disease
Evidence is amassing quickly that Chagas is a U.S. disease. But U.S. clinicians still lag in their knowledge of it, say physicians treating Chagas cases. “In medical school we get a 2-hour lecture on it, and it’s always been presented as an exotic disease and one you don’t treat,” Dr. Meymandi said.
The persistent perception of Chagas as a foreign disease means clinicians are inclined to dismiss positive results from a blood screening, particularly from someone who is not from Latin America. Yet cardiologists, ID practitioners, obstetricians, and primary care physicians all need to be aware that cases do occur in the United States and are potentially treatable.
Dr. Laila Woc-Colburn, an infectious disease and tropical medicine specialist at Baylor College of Medicine in Houston, said many people with Chagas never make it to an infectious disease specialist or cardiologist for a work-up. “When you test positive on serology [after a blood donation], you get a letter recommending you consult your physician. Most will go to their primary care doctors, who might say ‘this isn’t a disease in the United States.’ In Houston, that is often the case.”
Dr. Meymandi, who has treated hundreds of patients with Chagas with and without cardiac involvement, said any physician with a potential Chagas case must act. “If you get someone that’s positive, it’s your duty as a physician to confirm the positivity with CDC,” she said.
Dr. Yun concurred. “The most important message is, do something,” she said. “Don’t just assume it’s a false positive.”
Diagnosis is not simple and requires testing beyond the initial ELISA assay used in blood-bank screening. Confirmatory tests must be carried out in coordination with the Centers for Disease Control and Prevention. Also, with no agents approved by the Food and Drug Administration to treat Chagas, treatment is available only through the CDC’s investigational drugs protocol. Both drugs used in Chagas, benznidazole and nifurtimox, come with serious adverse effects that must be closely monitored.
“It’s time consuming, filling out the forms, getting the consent, tracking and sending back lab results to CDC in order to get drugs – it’s not like you can just write a prescription,” Dr. Meymandi said. But, “if you don’t know how to treat the patient or don’t have time, find someone like me,” she noted, adding that she is available to counsel any physician daunted by a potential Chagas case.
Treatment options
No formal clinical algorithm exists for Chagas, but Dr. Meymandi, Dr. Yun, and Dr. Woc-Colburn all pointed to a 2007 JAMA article, which describes diagnosis and treatment protocols, as an important reference for clinicians to start with. It’s “the best approximation of a clinical guideline we have,” Dr. Yun said (JAMA. 2007;298[18]:2171-81. doi:10.1001/jama.298.18.2171).
Dr. Meymandi, who has treated more Chagas patients than has any other U.S. clinician, said that treatment has changed somewhat since the JAMA article was published. In 2007, she said, nifurtimox was the main drug available through CDC, while benznidazole, which is somewhat better tolerated and has shorter treatment duration, has since become the first-line agent.
“We’ve lowered the dose of benznidazole, maxing out at 400 mg/day to decrease the toxicity,” she said. Also, treatment is now being extended to some patients aged 60 years and older.
The decision to treat or not treat, clinicians say, depends on the patient’s age, disease progression, comorbidities and potential serious drug interactions, and willingness to tolerate side effects that, with nifurtimox especially, can include skin sloughing, rash, and psychological and neurologic symptoms including depression and peripheral neuropathy.
“If you don’t have side effects, you’re not taking the drugs,” Dr. Meymandi said. Dr. Woc-Colburn noted that polypharmacy was a major consideration when treating older adults for Chagas. “If I have a patient who has diabetes, obesity, [and] end-stage renal disease, it’s not going to be ideal to give [benznidazole].”
Recent, highly anticipated results from BENEFIT, a large randomized trial (n = 2,854) showed that benznidazole reduced parasite load but was not helpful in halting cardiac damage at 5 years’ follow-up in patients with established Chagas cardiomyopathy (N Engl J Med. 2015 Oct;373:1295-306. doi:10.1056/NEJMoa1507574).
Dr. Meymandi, whose earlier research established that Chagas cardiomyopathy carries significantly higher morbidity and mortality than does non–Chagas cardiomyopathy (Circulation. 2012;126:A18171), said that the BENEFIT results underscore the need for physicians to be bullish in their approach to treating Chagas soon after diagnosis.
“It doesn’t matter if they’re symptomatic or asymptomatic. You can’t wait till they progress to treat. If you wait for the progression of disease you’ve lost the battle. You can’t wait and follow conservatively until you see the complications, because once those complications have started the parasitic load is too high for you to have an impact,” she said.
Dr. Yun said that given the toxicity of current treatment, she hoped to see more studies show clearer evidence of clinical benefit, “either reductions in mortality or reductions in end organ disease.” Most studies “have focused on clearance of parasite, which is important, but it’s not as important decreasing the risk of death or cardiomyopathy or heart failure.”
Rick Tarleton, Ph.D., a biologist the University of Georgia, in Athens, who has worked on Chagas for more than 30 years, said that because Chagas pathology is directly tied to parasite load – and not, as people have suggested in the past, an autoimmune reaction resulting from parasite exposure – drug treatment may prove to be worthwhile even in patients with significant cardiac involvement.
“You get rid of the parasite, you get rid of the progression of the disease,” Dr. Tarleton said. Even the findings from the BENEFIT trial, he said, did not lead him to conclude that treatment in people with established cardiac disease was futile.
“If you’re treating people who are already chronically infected and showing symptoms, the question is not have you reversed the damage, it’s have you stopped accumulating damage,” he noted. “And a 5-year follow-up is probably not long enough to know whether you’ve stopped accumulating.”
“We have drugs, they’re not great, they do have side effects, they don’t always work,” Dr. Tarleton said. “But they’re better than nothing. And they ought to be more widely used.”
Dr. Meymandi said that current supplies of benznidazole at CDC are low and that a dozen patients at her clinic are awaiting treatment. Meanwhile, access may soon be complicated further by the announcement, this month, that KaloBios Pharmaceuticals had bought the rights to seek FDA approval of benznidazole and market it in the United States.
The same company’s CEO came under fire in recent months for acquiring rights to an inexpensive drug to treat toxoplasmosis in AIDS patients, then announcing a price increase from $13.50 to $750 a pill.
“Everyone’s really concerned,” Dr. Meymandi said, “because Chagas is a disease of the poor.”
Psychoeducation program for military families improves function, reduces symptoms
SAN ANTONIO– As foreign wars wind down, and more families of military members and veterans receive care in civilian settings, an intervention used successfully on military bases to help families reduce risk of serious psychological disorders is being extended to civilian practices.
In the past decade, some 650,000 military and veteran family members have gone through Families Overcoming Under Stress, or FOCUS, a group of family-based interventions developed by a team led by psychiatrist Dr. Patricia E. Lester, director of the Nathanson Family Resilience Center at UCLA Health in Los Angeles.
Dr. Lester and her UCLA colleagues first adapted FOCUS at Marine Corps Base Camp Pendleton, San Diego, in 2006. Two years later, they implemented the program for the U.S. Navy Bureau of Medicine and Surgery at 22 Navy, Marine, Army, and Air Force installations in the United States and overseas. Now, with as many as 70% of active-duty military members living in civilian communities and about half of military-affiliated children getting health care in the civilian system, the program is being adapted to follow veterans’ families as they transition home.
The UCLA FOCUS team also is training community providers and extending technology platforms “to deliver our programs, monitor them, and put them in the hands of people where they live,” Dr. Lester said at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
New research from a longitudinal observational study assessing more than 2,600 families with children who participated in the program in the United States and Japan on military bases, published recently online, shows that the intervention has been well received, with about 70% of families completing it. In addition, its positive impact on psychological health outcomes for parents and children was sustained (J Am Acad Child Adolesc Psychiatry. 2015 [doi: http://dx.doi.org/10.1016/j.jaac.2015.10.009]).
“Consistently what we’ve found is that doing a preventive educational program early on is an opportunity to engage families before they may need mental health treatment – reducing anxiety, depression, and [posttraumatic stress disorder] in adults, strengthening family functioning, and improving internalizing and externalizing symptoms in kids,” Dr. Lester said.
The latest research is based on a secondary analysis of FOCUS data collected between 2008 and 2013. Significant improvements for parental anxiety, posttraumatic stress, and depression symptoms occurred in service member and civilian parents, and child anxiety symptoms improved in boys and girls. Importantly, those reductions were maintained 6 months after the intervention ended.
Roots of intervention
The model for FOCUS derives from two civilian interventions developed over the past 15 years, one of them for families in which a parent is depressed, and another for those in which a parent is medically ill. FOCUS also incorporated elements of a third intervention used with families living in postwar Bosnia-Herzegovina and in New York City after the terrorist attacks of Sept.11, 2001.
“We know from decades of developmental literature that if a parent is not doing well in terms of depression, anxiety, or PTSD, it represents an ongoing risk for children,” Dr. Lester said. In military and veteran populations, “family approaches are critical.”
About a third of combat service members and veterans are estimated to have depression, PTSD, or a traumatic brain injury – and an emerging body of research is showing that their children are at elevated risk for social, academic, and emotional problems.
The FOCUS program, which generally lasts 8 sessions over 6-8 weeks, starts with real-time web-based screening of psychological health measures, using a set of standardized behavioral health, family adjustment, and coping assessments to assess risk and customize the intervention. “We sit down with the family; we identify their strengths and where they may be having difficulties,” Dr. Lester said.
About a quarter of the parents in Dr. Lester’s study had clinically meaningful anxiety or depression symptoms at intake, with civilian spouses reporting slightly more than military members. Also, some 31% of civilian spouses had PTSD symptoms at baseline, compared with 26% of military members – an unexpected finding, Dr. Lester said. Among children, 35% of boys and 25% of girls had social difficulties at baseline.
Location of intervention is key
Rolling FOCUS out on military installations required attention to military family culture. A voluntary program, it was implemented to service members as a form of training, rather than counseling or a mental health intervention, though part of its objective was to help to bridge gaps to mental health treatment for those who needed it.
Importantly, the intervention was delivered in community centers or retail spaces in lieu of mental health facilities on bases. “Military families may be reluctant to come for behavioral health services because of stigma or concern about their job – the same barriers we see in civilian communities but amplified, because the risks are quite concrete,” Dr. Lester said.
Having the command structure embrace the program went a long way toward broadening adoption. “It was really important to get commanders to support the program and even to share that they have participated with their own children,” she said.
In the program, initial screening is followed by informational sessions with the UCLA-trained providers on the impact of military-related stressors on children, parents, and families.
In subsequent sessions, families start building a graphic family narrative timeline, with children over 6 and parents contributing their individual interpretations of past events – moves, deployments, life changes. On the military installations, the timelines are drawn on paper; many families in civilian settings, meanwhile, have worked remotely from their homes with providers at UCLA to create timelines on the computer.
“Then we do individual and family-level cognitive-behavioral skill building, such as emotional regulation, goal setting and problem solving,” Dr. Lester said. “We also help parents and children recognize and manage deployment reminders – including trauma and loss reminders,” she said. Family members work together to articulate their collective goals.
Benefits are sustained
Dr. Lester’s study looked at 3,499 parents and 3,810 children (average age, 7) who participated. Families averaged 4.5 deployments before taking part in the program.
At exit, percentages of clinically meaningful anxiety and depression symptoms decreased from approximately 23% of all parents at intake to about 11%, and remained similarly low at 1 month and 6 months after program completion (range of adjusted odds ratios: 0.29-0.36).
Both civilian and service member parents reported clinically meaningful and statistically significant decreases in PTSD symptoms, which was notable because the intervention was not designed as a clinical treatment program but rather a psychoeducation program.
Children older than 8 years saw significant improvements in self-reported anxiety symptoms, with prevalence from 14.5% at intake to 11.8% at follow up.
Transitioning with families
After its initial adaptation from civilian interventions, then its broad application and scaling up over a decade in military settings, FOCUS must now transition to communities where military and veteran families live.
Between 3 and 4 million military-connected children live in the United States, with about 2 million in families that have transitioned out of active-duty military. “In the population that we serve, the average 10-year-old kid has been through at least four deployments, two of them combat related,” with many individual and community level exposures to trauma and loss, Dr. Lester explained.
A parent’s leaving active duty does not necessarily change risk for families, she said in an interview. “Our observation is that there’s a lot of reactivity and reminders in these families that persist – when somebody comes back highly activated, when there are threats of separation, and fear and danger, and if you do have underlying PTSD risk, that reactivity can be reactivated even after transition to civilian life.”
Teams at UCLA work to train providers in the FOCUS interventions and certify them in the different models for couples or families with children. The UCLA team will travel to conduct training, or practitioners can train at UCLA.
“We’re taking these components that have been most effective and continuing to refine them and integrate them into systems so that they reach people where they’re living,” Dr. Lester said, adding that she would encourage any clinician working with military families to get in touch via the program’s website.
She said some of the lessons learned from adapting to a military setting apply in civilian contexts as well – including the emphasis of the program as training, rather than diagnosis and treatment.
“I don’t think it reduces the impact or relevance of the intervention to have [FOCUS] inside a traditional mental health setting,” she said. “But in settings where it is essential to reach out and engage people who might not be coming into the clinic, it is important to highlight that this is an educational preventive program.”
Dr. Lester’s group is now conducting a research study of one FOCUS early childhood intervention in community settings.
Like military families, civilian families also embrace the concept of preparedness, she said. “They want to feel they have the skills to navigate whatever challenges come their way.”
SAN ANTONIO– As foreign wars wind down, and more families of military members and veterans receive care in civilian settings, an intervention used successfully on military bases to help families reduce risk of serious psychological disorders is being extended to civilian practices.
In the past decade, some 650,000 military and veteran family members have gone through Families Overcoming Under Stress, or FOCUS, a group of family-based interventions developed by a team led by psychiatrist Dr. Patricia E. Lester, director of the Nathanson Family Resilience Center at UCLA Health in Los Angeles.
Dr. Lester and her UCLA colleagues first adapted FOCUS at Marine Corps Base Camp Pendleton, San Diego, in 2006. Two years later, they implemented the program for the U.S. Navy Bureau of Medicine and Surgery at 22 Navy, Marine, Army, and Air Force installations in the United States and overseas. Now, with as many as 70% of active-duty military members living in civilian communities and about half of military-affiliated children getting health care in the civilian system, the program is being adapted to follow veterans’ families as they transition home.
The UCLA FOCUS team also is training community providers and extending technology platforms “to deliver our programs, monitor them, and put them in the hands of people where they live,” Dr. Lester said at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
New research from a longitudinal observational study assessing more than 2,600 families with children who participated in the program in the United States and Japan on military bases, published recently online, shows that the intervention has been well received, with about 70% of families completing it. In addition, its positive impact on psychological health outcomes for parents and children was sustained (J Am Acad Child Adolesc Psychiatry. 2015 [doi: http://dx.doi.org/10.1016/j.jaac.2015.10.009]).
“Consistently what we’ve found is that doing a preventive educational program early on is an opportunity to engage families before they may need mental health treatment – reducing anxiety, depression, and [posttraumatic stress disorder] in adults, strengthening family functioning, and improving internalizing and externalizing symptoms in kids,” Dr. Lester said.
The latest research is based on a secondary analysis of FOCUS data collected between 2008 and 2013. Significant improvements for parental anxiety, posttraumatic stress, and depression symptoms occurred in service member and civilian parents, and child anxiety symptoms improved in boys and girls. Importantly, those reductions were maintained 6 months after the intervention ended.
Roots of intervention
The model for FOCUS derives from two civilian interventions developed over the past 15 years, one of them for families in which a parent is depressed, and another for those in which a parent is medically ill. FOCUS also incorporated elements of a third intervention used with families living in postwar Bosnia-Herzegovina and in New York City after the terrorist attacks of Sept.11, 2001.
“We know from decades of developmental literature that if a parent is not doing well in terms of depression, anxiety, or PTSD, it represents an ongoing risk for children,” Dr. Lester said. In military and veteran populations, “family approaches are critical.”
About a third of combat service members and veterans are estimated to have depression, PTSD, or a traumatic brain injury – and an emerging body of research is showing that their children are at elevated risk for social, academic, and emotional problems.
The FOCUS program, which generally lasts 8 sessions over 6-8 weeks, starts with real-time web-based screening of psychological health measures, using a set of standardized behavioral health, family adjustment, and coping assessments to assess risk and customize the intervention. “We sit down with the family; we identify their strengths and where they may be having difficulties,” Dr. Lester said.
About a quarter of the parents in Dr. Lester’s study had clinically meaningful anxiety or depression symptoms at intake, with civilian spouses reporting slightly more than military members. Also, some 31% of civilian spouses had PTSD symptoms at baseline, compared with 26% of military members – an unexpected finding, Dr. Lester said. Among children, 35% of boys and 25% of girls had social difficulties at baseline.
Location of intervention is key
Rolling FOCUS out on military installations required attention to military family culture. A voluntary program, it was implemented to service members as a form of training, rather than counseling or a mental health intervention, though part of its objective was to help to bridge gaps to mental health treatment for those who needed it.
Importantly, the intervention was delivered in community centers or retail spaces in lieu of mental health facilities on bases. “Military families may be reluctant to come for behavioral health services because of stigma or concern about their job – the same barriers we see in civilian communities but amplified, because the risks are quite concrete,” Dr. Lester said.
Having the command structure embrace the program went a long way toward broadening adoption. “It was really important to get commanders to support the program and even to share that they have participated with their own children,” she said.
In the program, initial screening is followed by informational sessions with the UCLA-trained providers on the impact of military-related stressors on children, parents, and families.
In subsequent sessions, families start building a graphic family narrative timeline, with children over 6 and parents contributing their individual interpretations of past events – moves, deployments, life changes. On the military installations, the timelines are drawn on paper; many families in civilian settings, meanwhile, have worked remotely from their homes with providers at UCLA to create timelines on the computer.
“Then we do individual and family-level cognitive-behavioral skill building, such as emotional regulation, goal setting and problem solving,” Dr. Lester said. “We also help parents and children recognize and manage deployment reminders – including trauma and loss reminders,” she said. Family members work together to articulate their collective goals.
Benefits are sustained
Dr. Lester’s study looked at 3,499 parents and 3,810 children (average age, 7) who participated. Families averaged 4.5 deployments before taking part in the program.
At exit, percentages of clinically meaningful anxiety and depression symptoms decreased from approximately 23% of all parents at intake to about 11%, and remained similarly low at 1 month and 6 months after program completion (range of adjusted odds ratios: 0.29-0.36).
Both civilian and service member parents reported clinically meaningful and statistically significant decreases in PTSD symptoms, which was notable because the intervention was not designed as a clinical treatment program but rather a psychoeducation program.
Children older than 8 years saw significant improvements in self-reported anxiety symptoms, with prevalence from 14.5% at intake to 11.8% at follow up.
Transitioning with families
After its initial adaptation from civilian interventions, then its broad application and scaling up over a decade in military settings, FOCUS must now transition to communities where military and veteran families live.
Between 3 and 4 million military-connected children live in the United States, with about 2 million in families that have transitioned out of active-duty military. “In the population that we serve, the average 10-year-old kid has been through at least four deployments, two of them combat related,” with many individual and community level exposures to trauma and loss, Dr. Lester explained.
A parent’s leaving active duty does not necessarily change risk for families, she said in an interview. “Our observation is that there’s a lot of reactivity and reminders in these families that persist – when somebody comes back highly activated, when there are threats of separation, and fear and danger, and if you do have underlying PTSD risk, that reactivity can be reactivated even after transition to civilian life.”
Teams at UCLA work to train providers in the FOCUS interventions and certify them in the different models for couples or families with children. The UCLA team will travel to conduct training, or practitioners can train at UCLA.
“We’re taking these components that have been most effective and continuing to refine them and integrate them into systems so that they reach people where they’re living,” Dr. Lester said, adding that she would encourage any clinician working with military families to get in touch via the program’s website.
She said some of the lessons learned from adapting to a military setting apply in civilian contexts as well – including the emphasis of the program as training, rather than diagnosis and treatment.
“I don’t think it reduces the impact or relevance of the intervention to have [FOCUS] inside a traditional mental health setting,” she said. “But in settings where it is essential to reach out and engage people who might not be coming into the clinic, it is important to highlight that this is an educational preventive program.”
Dr. Lester’s group is now conducting a research study of one FOCUS early childhood intervention in community settings.
Like military families, civilian families also embrace the concept of preparedness, she said. “They want to feel they have the skills to navigate whatever challenges come their way.”
SAN ANTONIO– As foreign wars wind down, and more families of military members and veterans receive care in civilian settings, an intervention used successfully on military bases to help families reduce risk of serious psychological disorders is being extended to civilian practices.
In the past decade, some 650,000 military and veteran family members have gone through Families Overcoming Under Stress, or FOCUS, a group of family-based interventions developed by a team led by psychiatrist Dr. Patricia E. Lester, director of the Nathanson Family Resilience Center at UCLA Health in Los Angeles.
Dr. Lester and her UCLA colleagues first adapted FOCUS at Marine Corps Base Camp Pendleton, San Diego, in 2006. Two years later, they implemented the program for the U.S. Navy Bureau of Medicine and Surgery at 22 Navy, Marine, Army, and Air Force installations in the United States and overseas. Now, with as many as 70% of active-duty military members living in civilian communities and about half of military-affiliated children getting health care in the civilian system, the program is being adapted to follow veterans’ families as they transition home.
The UCLA FOCUS team also is training community providers and extending technology platforms “to deliver our programs, monitor them, and put them in the hands of people where they live,” Dr. Lester said at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
New research from a longitudinal observational study assessing more than 2,600 families with children who participated in the program in the United States and Japan on military bases, published recently online, shows that the intervention has been well received, with about 70% of families completing it. In addition, its positive impact on psychological health outcomes for parents and children was sustained (J Am Acad Child Adolesc Psychiatry. 2015 [doi: http://dx.doi.org/10.1016/j.jaac.2015.10.009]).
“Consistently what we’ve found is that doing a preventive educational program early on is an opportunity to engage families before they may need mental health treatment – reducing anxiety, depression, and [posttraumatic stress disorder] in adults, strengthening family functioning, and improving internalizing and externalizing symptoms in kids,” Dr. Lester said.
The latest research is based on a secondary analysis of FOCUS data collected between 2008 and 2013. Significant improvements for parental anxiety, posttraumatic stress, and depression symptoms occurred in service member and civilian parents, and child anxiety symptoms improved in boys and girls. Importantly, those reductions were maintained 6 months after the intervention ended.
Roots of intervention
The model for FOCUS derives from two civilian interventions developed over the past 15 years, one of them for families in which a parent is depressed, and another for those in which a parent is medically ill. FOCUS also incorporated elements of a third intervention used with families living in postwar Bosnia-Herzegovina and in New York City after the terrorist attacks of Sept.11, 2001.
“We know from decades of developmental literature that if a parent is not doing well in terms of depression, anxiety, or PTSD, it represents an ongoing risk for children,” Dr. Lester said. In military and veteran populations, “family approaches are critical.”
About a third of combat service members and veterans are estimated to have depression, PTSD, or a traumatic brain injury – and an emerging body of research is showing that their children are at elevated risk for social, academic, and emotional problems.
The FOCUS program, which generally lasts 8 sessions over 6-8 weeks, starts with real-time web-based screening of psychological health measures, using a set of standardized behavioral health, family adjustment, and coping assessments to assess risk and customize the intervention. “We sit down with the family; we identify their strengths and where they may be having difficulties,” Dr. Lester said.
About a quarter of the parents in Dr. Lester’s study had clinically meaningful anxiety or depression symptoms at intake, with civilian spouses reporting slightly more than military members. Also, some 31% of civilian spouses had PTSD symptoms at baseline, compared with 26% of military members – an unexpected finding, Dr. Lester said. Among children, 35% of boys and 25% of girls had social difficulties at baseline.
Location of intervention is key
Rolling FOCUS out on military installations required attention to military family culture. A voluntary program, it was implemented to service members as a form of training, rather than counseling or a mental health intervention, though part of its objective was to help to bridge gaps to mental health treatment for those who needed it.
Importantly, the intervention was delivered in community centers or retail spaces in lieu of mental health facilities on bases. “Military families may be reluctant to come for behavioral health services because of stigma or concern about their job – the same barriers we see in civilian communities but amplified, because the risks are quite concrete,” Dr. Lester said.
Having the command structure embrace the program went a long way toward broadening adoption. “It was really important to get commanders to support the program and even to share that they have participated with their own children,” she said.
In the program, initial screening is followed by informational sessions with the UCLA-trained providers on the impact of military-related stressors on children, parents, and families.
In subsequent sessions, families start building a graphic family narrative timeline, with children over 6 and parents contributing their individual interpretations of past events – moves, deployments, life changes. On the military installations, the timelines are drawn on paper; many families in civilian settings, meanwhile, have worked remotely from their homes with providers at UCLA to create timelines on the computer.
“Then we do individual and family-level cognitive-behavioral skill building, such as emotional regulation, goal setting and problem solving,” Dr. Lester said. “We also help parents and children recognize and manage deployment reminders – including trauma and loss reminders,” she said. Family members work together to articulate their collective goals.
Benefits are sustained
Dr. Lester’s study looked at 3,499 parents and 3,810 children (average age, 7) who participated. Families averaged 4.5 deployments before taking part in the program.
At exit, percentages of clinically meaningful anxiety and depression symptoms decreased from approximately 23% of all parents at intake to about 11%, and remained similarly low at 1 month and 6 months after program completion (range of adjusted odds ratios: 0.29-0.36).
Both civilian and service member parents reported clinically meaningful and statistically significant decreases in PTSD symptoms, which was notable because the intervention was not designed as a clinical treatment program but rather a psychoeducation program.
Children older than 8 years saw significant improvements in self-reported anxiety symptoms, with prevalence from 14.5% at intake to 11.8% at follow up.
Transitioning with families
After its initial adaptation from civilian interventions, then its broad application and scaling up over a decade in military settings, FOCUS must now transition to communities where military and veteran families live.
Between 3 and 4 million military-connected children live in the United States, with about 2 million in families that have transitioned out of active-duty military. “In the population that we serve, the average 10-year-old kid has been through at least four deployments, two of them combat related,” with many individual and community level exposures to trauma and loss, Dr. Lester explained.
A parent’s leaving active duty does not necessarily change risk for families, she said in an interview. “Our observation is that there’s a lot of reactivity and reminders in these families that persist – when somebody comes back highly activated, when there are threats of separation, and fear and danger, and if you do have underlying PTSD risk, that reactivity can be reactivated even after transition to civilian life.”
Teams at UCLA work to train providers in the FOCUS interventions and certify them in the different models for couples or families with children. The UCLA team will travel to conduct training, or practitioners can train at UCLA.
“We’re taking these components that have been most effective and continuing to refine them and integrate them into systems so that they reach people where they’re living,” Dr. Lester said, adding that she would encourage any clinician working with military families to get in touch via the program’s website.
She said some of the lessons learned from adapting to a military setting apply in civilian contexts as well – including the emphasis of the program as training, rather than diagnosis and treatment.
“I don’t think it reduces the impact or relevance of the intervention to have [FOCUS] inside a traditional mental health setting,” she said. “But in settings where it is essential to reach out and engage people who might not be coming into the clinic, it is important to highlight that this is an educational preventive program.”
Dr. Lester’s group is now conducting a research study of one FOCUS early childhood intervention in community settings.
Like military families, civilian families also embrace the concept of preparedness, she said. “They want to feel they have the skills to navigate whatever challenges come their way.”
EXPERT ANALYSIS AT THE AACAP ANNUAL MEETING
FDA approves first recombinant von Willebrand treatment
The first recombinant von Willebrand factor has been approved for von Willebrand disease, the Food and Drug Administration announced.
Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in the Dec. 8 statement that the approval “provides an additional therapeutic option for the treatment of bleeding episodes in patients with von Willebrand disease.”
The product was approved for on-demand therapy for bleeding episodes in adults with the disorder, which affects up to 1% of the U.S. population. Current treatment options include desmopressin and plasma-derived von Willebrand factor/factor VIII concentrates. The latter are limited by donor availability and are variable in the factor VIII levels they contain.
The new treatment, marketed as Vonvendi (Baxalta), is administered by infusion. The product contains only trace amounts of factor VIII, allowing for administration of factor VIII only as needed.
In a phase III manufacturer-sponsored nonrandomized trial of 22 subjects, bleeding was controlled with a single infusion in 82% of 192 bleeding episodes, according to a Baxalta press release. Patients with major bleeding required as many as four infusions, but treatment was effective in all subjects and 97% had an excellent efficacy rating and the remaining 3% had a good efficacy rating.
The most common adverse event was pruritus. No thrombotic events or severe allergic reactions were reported. Patients did not develop neutralizing antibodies against von Willebrand factor or factor VIII during the course of the study.
In its news release, the manufacturer said it is building a clinical development program to increase patient access to the treatment and evaluate its use in “prophylaxis, surgical, and pediatric indications.” Vonvendi is expected to be available in late 2016.
The first recombinant von Willebrand factor has been approved for von Willebrand disease, the Food and Drug Administration announced.
Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in the Dec. 8 statement that the approval “provides an additional therapeutic option for the treatment of bleeding episodes in patients with von Willebrand disease.”
The product was approved for on-demand therapy for bleeding episodes in adults with the disorder, which affects up to 1% of the U.S. population. Current treatment options include desmopressin and plasma-derived von Willebrand factor/factor VIII concentrates. The latter are limited by donor availability and are variable in the factor VIII levels they contain.
The new treatment, marketed as Vonvendi (Baxalta), is administered by infusion. The product contains only trace amounts of factor VIII, allowing for administration of factor VIII only as needed.
In a phase III manufacturer-sponsored nonrandomized trial of 22 subjects, bleeding was controlled with a single infusion in 82% of 192 bleeding episodes, according to a Baxalta press release. Patients with major bleeding required as many as four infusions, but treatment was effective in all subjects and 97% had an excellent efficacy rating and the remaining 3% had a good efficacy rating.
The most common adverse event was pruritus. No thrombotic events or severe allergic reactions were reported. Patients did not develop neutralizing antibodies against von Willebrand factor or factor VIII during the course of the study.
In its news release, the manufacturer said it is building a clinical development program to increase patient access to the treatment and evaluate its use in “prophylaxis, surgical, and pediatric indications.” Vonvendi is expected to be available in late 2016.
The first recombinant von Willebrand factor has been approved for von Willebrand disease, the Food and Drug Administration announced.
Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in the Dec. 8 statement that the approval “provides an additional therapeutic option for the treatment of bleeding episodes in patients with von Willebrand disease.”
The product was approved for on-demand therapy for bleeding episodes in adults with the disorder, which affects up to 1% of the U.S. population. Current treatment options include desmopressin and plasma-derived von Willebrand factor/factor VIII concentrates. The latter are limited by donor availability and are variable in the factor VIII levels they contain.
The new treatment, marketed as Vonvendi (Baxalta), is administered by infusion. The product contains only trace amounts of factor VIII, allowing for administration of factor VIII only as needed.
In a phase III manufacturer-sponsored nonrandomized trial of 22 subjects, bleeding was controlled with a single infusion in 82% of 192 bleeding episodes, according to a Baxalta press release. Patients with major bleeding required as many as four infusions, but treatment was effective in all subjects and 97% had an excellent efficacy rating and the remaining 3% had a good efficacy rating.
The most common adverse event was pruritus. No thrombotic events or severe allergic reactions were reported. Patients did not develop neutralizing antibodies against von Willebrand factor or factor VIII during the course of the study.
In its news release, the manufacturer said it is building a clinical development program to increase patient access to the treatment and evaluate its use in “prophylaxis, surgical, and pediatric indications.” Vonvendi is expected to be available in late 2016.
Steroid use down, biologic use rising in pregnancies of women with rheumatic disease
Steroids and hydroxychloroquine remain the most widely prescribed treatment options for pregnant women with rheumatologic diseases, according to a study looking at prescribing patterns in a cohort of women diagnosed with systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
Lead investigator Dr. Rishi J. Desai of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his colleagues found that the use of biologic agents during pregnancy, though still low, rose for 2,645 women from all regions of the United States covered by private insurance or Medicaid between 2001 and 2012. The investigators evaluated prescription filling records for steroids, nonbiologic disease-modifying agents, and biologics. The women in the study all had live births. Dr. Desai and his colleagues looked at scripts for individual agents filled in the 3-month period prior to each woman’s pregnancy and during her pregnancy (Arthritis Rheumatol. 2015 Nov 25. doi: 10.1002/art.39521).
Nearly two-thirds of women with psoriatic arthritis or ankylosing spondylitis stopped filling immunomodulatory prescriptions during their pregnancies, while only 26% of lupus and 34.5% of rheumatoid arthritis patients did so. In the cohort as a whole, steroids and hydroxychloroquine were the most frequently used agents in pregnancy (48.4% and 27.1%, respectively). Steroid use during pregnancy dropped over time, from 54.4 per 100 deliveries to 42.4 between 2001 and 2012, while rates for biologics increased from 5.1 per 100 to 16.6 (P less than .001 for both trends).
“More comparative research on the safety of steroids as well as disease-modifying agents used during pregnancy will be critical for providing the necessary evidence to guide treatment decisions in future,” Dr. Desai and his colleagues wrote in their analysis.
The findings also suggest, the investigators wrote, “that with availability of some reassuring data indicating absence of a major fetal adverse event after biologic use in pregnancy, physicians have become more comfortable with continuing treatment with these agents.”
Use of agents potentially harmful to a developing fetus, including methotrexate, mycophenolate mofetil, and leflunomide, was very low in the study. However, the investigators noted, because their study enrolled only women with successful pregnancies, it could have underestimated the use of some of these agents, as women using them may have chosen to terminate their pregnancies.
The study received no outside funding. Two coauthors reported financial relationships with AstraZeneca, and one of them also reported funding from Pfizer and Eli Lilly.
Steroids and hydroxychloroquine remain the most widely prescribed treatment options for pregnant women with rheumatologic diseases, according to a study looking at prescribing patterns in a cohort of women diagnosed with systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
Lead investigator Dr. Rishi J. Desai of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his colleagues found that the use of biologic agents during pregnancy, though still low, rose for 2,645 women from all regions of the United States covered by private insurance or Medicaid between 2001 and 2012. The investigators evaluated prescription filling records for steroids, nonbiologic disease-modifying agents, and biologics. The women in the study all had live births. Dr. Desai and his colleagues looked at scripts for individual agents filled in the 3-month period prior to each woman’s pregnancy and during her pregnancy (Arthritis Rheumatol. 2015 Nov 25. doi: 10.1002/art.39521).
Nearly two-thirds of women with psoriatic arthritis or ankylosing spondylitis stopped filling immunomodulatory prescriptions during their pregnancies, while only 26% of lupus and 34.5% of rheumatoid arthritis patients did so. In the cohort as a whole, steroids and hydroxychloroquine were the most frequently used agents in pregnancy (48.4% and 27.1%, respectively). Steroid use during pregnancy dropped over time, from 54.4 per 100 deliveries to 42.4 between 2001 and 2012, while rates for biologics increased from 5.1 per 100 to 16.6 (P less than .001 for both trends).
“More comparative research on the safety of steroids as well as disease-modifying agents used during pregnancy will be critical for providing the necessary evidence to guide treatment decisions in future,” Dr. Desai and his colleagues wrote in their analysis.
The findings also suggest, the investigators wrote, “that with availability of some reassuring data indicating absence of a major fetal adverse event after biologic use in pregnancy, physicians have become more comfortable with continuing treatment with these agents.”
Use of agents potentially harmful to a developing fetus, including methotrexate, mycophenolate mofetil, and leflunomide, was very low in the study. However, the investigators noted, because their study enrolled only women with successful pregnancies, it could have underestimated the use of some of these agents, as women using them may have chosen to terminate their pregnancies.
The study received no outside funding. Two coauthors reported financial relationships with AstraZeneca, and one of them also reported funding from Pfizer and Eli Lilly.
Steroids and hydroxychloroquine remain the most widely prescribed treatment options for pregnant women with rheumatologic diseases, according to a study looking at prescribing patterns in a cohort of women diagnosed with systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
Lead investigator Dr. Rishi J. Desai of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his colleagues found that the use of biologic agents during pregnancy, though still low, rose for 2,645 women from all regions of the United States covered by private insurance or Medicaid between 2001 and 2012. The investigators evaluated prescription filling records for steroids, nonbiologic disease-modifying agents, and biologics. The women in the study all had live births. Dr. Desai and his colleagues looked at scripts for individual agents filled in the 3-month period prior to each woman’s pregnancy and during her pregnancy (Arthritis Rheumatol. 2015 Nov 25. doi: 10.1002/art.39521).
Nearly two-thirds of women with psoriatic arthritis or ankylosing spondylitis stopped filling immunomodulatory prescriptions during their pregnancies, while only 26% of lupus and 34.5% of rheumatoid arthritis patients did so. In the cohort as a whole, steroids and hydroxychloroquine were the most frequently used agents in pregnancy (48.4% and 27.1%, respectively). Steroid use during pregnancy dropped over time, from 54.4 per 100 deliveries to 42.4 between 2001 and 2012, while rates for biologics increased from 5.1 per 100 to 16.6 (P less than .001 for both trends).
“More comparative research on the safety of steroids as well as disease-modifying agents used during pregnancy will be critical for providing the necessary evidence to guide treatment decisions in future,” Dr. Desai and his colleagues wrote in their analysis.
The findings also suggest, the investigators wrote, “that with availability of some reassuring data indicating absence of a major fetal adverse event after biologic use in pregnancy, physicians have become more comfortable with continuing treatment with these agents.”
Use of agents potentially harmful to a developing fetus, including methotrexate, mycophenolate mofetil, and leflunomide, was very low in the study. However, the investigators noted, because their study enrolled only women with successful pregnancies, it could have underestimated the use of some of these agents, as women using them may have chosen to terminate their pregnancies.
The study received no outside funding. Two coauthors reported financial relationships with AstraZeneca, and one of them also reported funding from Pfizer and Eli Lilly.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Women with lupus and other rheumatic diseases used fewer steroids during pregnancy over a 12-year period, while use of biologic agents increased over time.
Major finding: Steroid use dropped from 54.4 per 100 deliveries to 42.4 between 2001 and 2012, while biologic use increased from 5.1 per 100 to 16.6 (P less than .001 for both).
Data source: Private and public insurance records, including prescription filling data, for 2,645 U.S. women with lupus, rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis who gave birth between 2001 and 2012.
Disclosures: The study received no outside funding. Two coauthors reported financial relationships with pharmaceutical manufacturers.
Psoriasis Cohort Reveals High Arthritis Risk
Psoriatic arthritis may occur more frequently among people with psoriasis than previously reported, and risk factors include having severe psoriasis, nail pitting, low education levels, and uveitis, according to findings from a Canadian cohort study.
Beginning in 2006, Dr. Lihi Eder of the University of Toronto and coinvestigators recruited 464 patients (mean age 47, 56% male, 77% white) mainly from phototherapy and dermatology outpatient clinics in Toronto, and followed them 8 years. All had psoriasis of varying type and severity at baseline, but not inflammatory arthritis or spondylitis (Arthritis Rheumatol. 2015 Nov 10 doi: 10.1002/art.39494).
During the 8-year follow-up, 51 patients developed rheumatologist-confirmed psoriatic arthritis (PsA). Dr. Eder and colleagues reported an annual incidence rate of 2.7 confirmed cases of psoriatic arthritis per 100 psoriasis patients per year, which is considerably higher than previous published estimates, the investigators noted. The independent predictors of confirmed psoriatic arthritis were severe psoriasis (relative risk, 5.4; P = .006), not finishing high school (vs. finishing college RR, 4.5, P = .005; and vs. finishing high school RR, 3.3; P = .049), and use of systemic retinoids (RR, 3.4; P = .02). Time-dependent predictive variables included psoriatic nail pitting (RR, 2.5; P = .002) and uveitis (RR, 31.5; P = .001). Disease severity and nail pitting have been found in previous studies to be associated with a higher risk of psoriatic arthritis.
This study confirmed this association and also identified low education levels and uveitis as predictors. Low education is a marker of socioeconomic status that has been associated with lifestyle habits and possibly occupations that may increase PsA risk, the study authors noted, but the link requires further investigation. The authors cautioned that only three uveitis cases occurred in the cohort and that confidence intervals were wide. They also noted as a limitation that most participants were recruited from dermatology clinics, leading to overrepresentation of moderate-severe psoriasis and possibly patients with longer disease duration. Nevertheless, it “is likely that the true incidence of PsA in patients with psoriasis, particularly those attending dermatology clinics, is higher than previously reported,” the investigators wrote. “This highlights the role of dermatologists as key players in identifying psoriasis patients who are at higher risk of developing PsA.”
Krembil Foundation, the Canadian Institutes of Health Research, and The Arthritis Society supported the study.
Psoriatic arthritis may occur more frequently among people with psoriasis than previously reported, and risk factors include having severe psoriasis, nail pitting, low education levels, and uveitis, according to findings from a Canadian cohort study.
Beginning in 2006, Dr. Lihi Eder of the University of Toronto and coinvestigators recruited 464 patients (mean age 47, 56% male, 77% white) mainly from phototherapy and dermatology outpatient clinics in Toronto, and followed them 8 years. All had psoriasis of varying type and severity at baseline, but not inflammatory arthritis or spondylitis (Arthritis Rheumatol. 2015 Nov 10 doi: 10.1002/art.39494).
During the 8-year follow-up, 51 patients developed rheumatologist-confirmed psoriatic arthritis (PsA). Dr. Eder and colleagues reported an annual incidence rate of 2.7 confirmed cases of psoriatic arthritis per 100 psoriasis patients per year, which is considerably higher than previous published estimates, the investigators noted. The independent predictors of confirmed psoriatic arthritis were severe psoriasis (relative risk, 5.4; P = .006), not finishing high school (vs. finishing college RR, 4.5, P = .005; and vs. finishing high school RR, 3.3; P = .049), and use of systemic retinoids (RR, 3.4; P = .02). Time-dependent predictive variables included psoriatic nail pitting (RR, 2.5; P = .002) and uveitis (RR, 31.5; P = .001). Disease severity and nail pitting have been found in previous studies to be associated with a higher risk of psoriatic arthritis.
This study confirmed this association and also identified low education levels and uveitis as predictors. Low education is a marker of socioeconomic status that has been associated with lifestyle habits and possibly occupations that may increase PsA risk, the study authors noted, but the link requires further investigation. The authors cautioned that only three uveitis cases occurred in the cohort and that confidence intervals were wide. They also noted as a limitation that most participants were recruited from dermatology clinics, leading to overrepresentation of moderate-severe psoriasis and possibly patients with longer disease duration. Nevertheless, it “is likely that the true incidence of PsA in patients with psoriasis, particularly those attending dermatology clinics, is higher than previously reported,” the investigators wrote. “This highlights the role of dermatologists as key players in identifying psoriasis patients who are at higher risk of developing PsA.”
Krembil Foundation, the Canadian Institutes of Health Research, and The Arthritis Society supported the study.
Psoriatic arthritis may occur more frequently among people with psoriasis than previously reported, and risk factors include having severe psoriasis, nail pitting, low education levels, and uveitis, according to findings from a Canadian cohort study.
Beginning in 2006, Dr. Lihi Eder of the University of Toronto and coinvestigators recruited 464 patients (mean age 47, 56% male, 77% white) mainly from phototherapy and dermatology outpatient clinics in Toronto, and followed them 8 years. All had psoriasis of varying type and severity at baseline, but not inflammatory arthritis or spondylitis (Arthritis Rheumatol. 2015 Nov 10 doi: 10.1002/art.39494).
During the 8-year follow-up, 51 patients developed rheumatologist-confirmed psoriatic arthritis (PsA). Dr. Eder and colleagues reported an annual incidence rate of 2.7 confirmed cases of psoriatic arthritis per 100 psoriasis patients per year, which is considerably higher than previous published estimates, the investigators noted. The independent predictors of confirmed psoriatic arthritis were severe psoriasis (relative risk, 5.4; P = .006), not finishing high school (vs. finishing college RR, 4.5, P = .005; and vs. finishing high school RR, 3.3; P = .049), and use of systemic retinoids (RR, 3.4; P = .02). Time-dependent predictive variables included psoriatic nail pitting (RR, 2.5; P = .002) and uveitis (RR, 31.5; P = .001). Disease severity and nail pitting have been found in previous studies to be associated with a higher risk of psoriatic arthritis.
This study confirmed this association and also identified low education levels and uveitis as predictors. Low education is a marker of socioeconomic status that has been associated with lifestyle habits and possibly occupations that may increase PsA risk, the study authors noted, but the link requires further investigation. The authors cautioned that only three uveitis cases occurred in the cohort and that confidence intervals were wide. They also noted as a limitation that most participants were recruited from dermatology clinics, leading to overrepresentation of moderate-severe psoriasis and possibly patients with longer disease duration. Nevertheless, it “is likely that the true incidence of PsA in patients with psoriasis, particularly those attending dermatology clinics, is higher than previously reported,” the investigators wrote. “This highlights the role of dermatologists as key players in identifying psoriasis patients who are at higher risk of developing PsA.”
Krembil Foundation, the Canadian Institutes of Health Research, and The Arthritis Society supported the study.
FROM ARTHRITIS & RHEUMATOLOGY
Psoriasis cohort reveals high arthritis risk
Psoriatic arthritis may occur more frequently among people with psoriasis than previously reported, and risk factors include having severe psoriasis, nail pitting, low education levels, and uveitis, according to findings from a Canadian cohort study.
Beginning in 2006, Dr. Lihi Eder of the University of Toronto and coinvestigators recruited 464 patients (mean age 47, 56% male, 77% white) mainly from phototherapy and dermatology outpatient clinics in Toronto, and followed them 8 years. All had psoriasis of varying type and severity at baseline, but not inflammatory arthritis or spondylitis (Arthritis Rheumatol. 2015 Nov 10 doi: 10.1002/art.39494).
During the 8-year follow-up, 51 patients developed rheumatologist-confirmed psoriatic arthritis (PsA). Dr. Eder and colleagues reported an annual incidence rate of 2.7 confirmed cases of psoriatic arthritis per 100 psoriasis patients per year, which is considerably higher than previous published estimates, the investigators noted. The independent predictors of confirmed psoriatic arthritis were severe psoriasis (relative risk, 5.4; P = .006), not finishing high school (vs. finishing college RR, 4.5, P = .005; and vs. finishing high school RR, 3.3; P = .049), and use of systemic retinoids (RR, 3.4; P = .02). Time-dependent predictive variables included psoriatic nail pitting (RR, 2.5; P = .002) and uveitis (RR, 31.5; P = .001). Disease severity and nail pitting have been found in previous studies to be associated with a higher risk of psoriatic arthritis.
This study confirmed this association and also identified low education levels and uveitis as predictors. Low education is a marker of socioeconomic status that has been associated with lifestyle habits and possibly occupations that may increase PsA risk, the study authors noted, but the link requires further investigation. The authors cautioned that only three uveitis cases occurred in the cohort and that confidence intervals were wide. They also noted as a limitation that most participants were recruited from dermatology clinics, leading to overrepresentation of moderate-severe psoriasis and possibly patients with longer disease duration. Nevertheless, it “is likely that the true incidence of PsA in patients with psoriasis, particularly those attending dermatology clinics, is higher than previously reported,” the investigators wrote. “This highlights the role of dermatologists as key players in identifying psoriasis patients who are at higher risk of developing PsA.”
Krembil Foundation, the Canadian Institutes of Health Research, and The Arthritis Society supported the study.
Psoriatic arthritis may occur more frequently among people with psoriasis than previously reported, and risk factors include having severe psoriasis, nail pitting, low education levels, and uveitis, according to findings from a Canadian cohort study.
Beginning in 2006, Dr. Lihi Eder of the University of Toronto and coinvestigators recruited 464 patients (mean age 47, 56% male, 77% white) mainly from phototherapy and dermatology outpatient clinics in Toronto, and followed them 8 years. All had psoriasis of varying type and severity at baseline, but not inflammatory arthritis or spondylitis (Arthritis Rheumatol. 2015 Nov 10 doi: 10.1002/art.39494).
During the 8-year follow-up, 51 patients developed rheumatologist-confirmed psoriatic arthritis (PsA). Dr. Eder and colleagues reported an annual incidence rate of 2.7 confirmed cases of psoriatic arthritis per 100 psoriasis patients per year, which is considerably higher than previous published estimates, the investigators noted. The independent predictors of confirmed psoriatic arthritis were severe psoriasis (relative risk, 5.4; P = .006), not finishing high school (vs. finishing college RR, 4.5, P = .005; and vs. finishing high school RR, 3.3; P = .049), and use of systemic retinoids (RR, 3.4; P = .02). Time-dependent predictive variables included psoriatic nail pitting (RR, 2.5; P = .002) and uveitis (RR, 31.5; P = .001). Disease severity and nail pitting have been found in previous studies to be associated with a higher risk of psoriatic arthritis.
This study confirmed this association and also identified low education levels and uveitis as predictors. Low education is a marker of socioeconomic status that has been associated with lifestyle habits and possibly occupations that may increase PsA risk, the study authors noted, but the link requires further investigation. The authors cautioned that only three uveitis cases occurred in the cohort and that confidence intervals were wide. They also noted as a limitation that most participants were recruited from dermatology clinics, leading to overrepresentation of moderate-severe psoriasis and possibly patients with longer disease duration. Nevertheless, it “is likely that the true incidence of PsA in patients with psoriasis, particularly those attending dermatology clinics, is higher than previously reported,” the investigators wrote. “This highlights the role of dermatologists as key players in identifying psoriasis patients who are at higher risk of developing PsA.”
Krembil Foundation, the Canadian Institutes of Health Research, and The Arthritis Society supported the study.
Psoriatic arthritis may occur more frequently among people with psoriasis than previously reported, and risk factors include having severe psoriasis, nail pitting, low education levels, and uveitis, according to findings from a Canadian cohort study.
Beginning in 2006, Dr. Lihi Eder of the University of Toronto and coinvestigators recruited 464 patients (mean age 47, 56% male, 77% white) mainly from phototherapy and dermatology outpatient clinics in Toronto, and followed them 8 years. All had psoriasis of varying type and severity at baseline, but not inflammatory arthritis or spondylitis (Arthritis Rheumatol. 2015 Nov 10 doi: 10.1002/art.39494).
During the 8-year follow-up, 51 patients developed rheumatologist-confirmed psoriatic arthritis (PsA). Dr. Eder and colleagues reported an annual incidence rate of 2.7 confirmed cases of psoriatic arthritis per 100 psoriasis patients per year, which is considerably higher than previous published estimates, the investigators noted. The independent predictors of confirmed psoriatic arthritis were severe psoriasis (relative risk, 5.4; P = .006), not finishing high school (vs. finishing college RR, 4.5, P = .005; and vs. finishing high school RR, 3.3; P = .049), and use of systemic retinoids (RR, 3.4; P = .02). Time-dependent predictive variables included psoriatic nail pitting (RR, 2.5; P = .002) and uveitis (RR, 31.5; P = .001). Disease severity and nail pitting have been found in previous studies to be associated with a higher risk of psoriatic arthritis.
This study confirmed this association and also identified low education levels and uveitis as predictors. Low education is a marker of socioeconomic status that has been associated with lifestyle habits and possibly occupations that may increase PsA risk, the study authors noted, but the link requires further investigation. The authors cautioned that only three uveitis cases occurred in the cohort and that confidence intervals were wide. They also noted as a limitation that most participants were recruited from dermatology clinics, leading to overrepresentation of moderate-severe psoriasis and possibly patients with longer disease duration. Nevertheless, it “is likely that the true incidence of PsA in patients with psoriasis, particularly those attending dermatology clinics, is higher than previously reported,” the investigators wrote. “This highlights the role of dermatologists as key players in identifying psoriasis patients who are at higher risk of developing PsA.”
Krembil Foundation, the Canadian Institutes of Health Research, and The Arthritis Society supported the study.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Incidence of psoriatic arthritis is higher among psoriasis patients than previously estimated.
Major finding: Annual incidence rate was 2.7 (95% confidence interval 2.1, 3.6) PsA cases per 100 psoriasis patients; significant predictors included disease severity, nail pitting, low education, and uveitis.
Data source: A prospective cohort study of 464 psoriasis patients without arthritis at baseline, followed for 8 years.
Disclosures: Krembil Foundation, Canadian Institutes of Health Research, and The Arthritis Society sponsored the study.
