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An Update on the Diagnosis and Treatment of Hidradenitis Suppurativa
Hidradenitis suppurativa (HS) is a chronic, inflammatory, scarring disease that occurs most frequently along the milk lines of the body from axillae to groin, is most common in the second and third decades of life, and is rarely observed before puberty. It disproportionately affects women and is associated with a host of comorbidities and dramatically reduced quality of life. The delay from HS symptom onset to diagnosis is approximately 7 years, with drastic consequences for patient well being. Early diagnosis and treatment are of paramount importance. While several nonpharmacologic, pharmacologic, and surgical treatment modalities exist for HS, only one agent, adalimumab, has been approved by the US Food and Drug Administration for this indication. Lifestyle modifications, dietary changes, patient education, and psychosocial support are important components of HS therapy.
Hidradenitis suppurativa (HS) is a chronic, inflammatory, scarring disease that occurs most frequently along the milk lines of the body from axillae to groin, is most common in the second and third decades of life, and is rarely observed before puberty. It disproportionately affects women and is associated with a host of comorbidities and dramatically reduced quality of life. The delay from HS symptom onset to diagnosis is approximately 7 years, with drastic consequences for patient well being. Early diagnosis and treatment are of paramount importance. While several nonpharmacologic, pharmacologic, and surgical treatment modalities exist for HS, only one agent, adalimumab, has been approved by the US Food and Drug Administration for this indication. Lifestyle modifications, dietary changes, patient education, and psychosocial support are important components of HS therapy.
Hidradenitis suppurativa (HS) is a chronic, inflammatory, scarring disease that occurs most frequently along the milk lines of the body from axillae to groin, is most common in the second and third decades of life, and is rarely observed before puberty. It disproportionately affects women and is associated with a host of comorbidities and dramatically reduced quality of life. The delay from HS symptom onset to diagnosis is approximately 7 years, with drastic consequences for patient well being. Early diagnosis and treatment are of paramount importance. While several nonpharmacologic, pharmacologic, and surgical treatment modalities exist for HS, only one agent, adalimumab, has been approved by the US Food and Drug Administration for this indication. Lifestyle modifications, dietary changes, patient education, and psychosocial support are important components of HS therapy.
Poor stewardship
To those of us who live and practice in the northeast, it comes as no surprise that the mortality rate for middle class whites is climbing. Obituaries in our local papers often include men and women in their forties “dying at home,” with no mention of cancer or chronic disease. Rarely, the family can bring itself to announce that their loved one has died of a drug overdose.
Deaths attributable to prescription opioid overdoses quadrupled in the decade from 1999 to 2010, and the trend shows little sign of abating as the number of prescriptions for opioids has risen tenfold over the last 20 years (“How Doctors Helped Drive the Addiction Crisis,” by Dr. Richard Friedman, New York Times, Nov. 7, 2015). Could physician behavior have contributed to outbreak of this deadly plague of addiction? That is like asking if something the zookeeper did or didn’t do could have been responsible for the escape of the man-eating tiger that is devouring the neighborhood children. Regardless of what other factors might be responsible for the epidemic of fatal prescription opioid overdoses, physicians must admit some culpability.
Until recently, I assumed that the problem of prescription opioids finding their way to addicts was unique to physicians treating adults. However, a study reported at the annual meeting of the American Society of Anesthesiologists reveals pediatricians and other clinicians prescribing for children must share in the blame.
Dr. Myron Yaster at Johns Hopkins University Hospital, Baltimore, has found that in a group of nearly 300 pediatric patients (average age, 11 years and average weight of 44 kg), overall the patients used only 42% of the prescribed amount of opioids. Almost half of the patients had a teenage sibling, a group that Dr. Yaster describes as the “target population of drug abuse.”
What’s going on here? Some of the problem dates back to the 1990s when physicians were urged to shift their focus toward the problem of inadequately treated pain. With the help of nurses armed with pain-rating schemes and smiley/grumpy face charts, the mantra became “no pain shall go unmedicated,” when the better response should have been “no pain shall go unmanaged.” But good pain management takes time. It requires that the physician and staff consider each patient as a unique individual. In many cases, reassurance and education can make a non–opioid medication or even no medication a better choice.
However, according to Dr. Yaster, “leftover medicine is the most important element in drug addiction.” Why did physicians prescribe 10 days of medication when his study revealed that most patients took the medication for only 5? It could just be a bad habit. Or it could be ignorance or inexperience. How many physicians ask at follow-up appointments “How long did you take your medication? Tell me the history of your pain.”
Or could it be that physicians are simply trying to prevent those annoying calls from patients who have run out of their medication? Dr. Yaster’s findings suggest that those calls would be few and far between. More careful thought into how much medication we prescribe also would mean that when a patient called for more medication that there was a problem. Either the patient’s recuperation has hit a worrisome bump in the road or possibly her medication is being diverted.
History tells us that physicians, even pediatricians, have been poor stewards of the powerful medications with which we have been entrusted. First, it was antibiotics and now opioids have joined the list.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].
To those of us who live and practice in the northeast, it comes as no surprise that the mortality rate for middle class whites is climbing. Obituaries in our local papers often include men and women in their forties “dying at home,” with no mention of cancer or chronic disease. Rarely, the family can bring itself to announce that their loved one has died of a drug overdose.
Deaths attributable to prescription opioid overdoses quadrupled in the decade from 1999 to 2010, and the trend shows little sign of abating as the number of prescriptions for opioids has risen tenfold over the last 20 years (“How Doctors Helped Drive the Addiction Crisis,” by Dr. Richard Friedman, New York Times, Nov. 7, 2015). Could physician behavior have contributed to outbreak of this deadly plague of addiction? That is like asking if something the zookeeper did or didn’t do could have been responsible for the escape of the man-eating tiger that is devouring the neighborhood children. Regardless of what other factors might be responsible for the epidemic of fatal prescription opioid overdoses, physicians must admit some culpability.
Until recently, I assumed that the problem of prescription opioids finding their way to addicts was unique to physicians treating adults. However, a study reported at the annual meeting of the American Society of Anesthesiologists reveals pediatricians and other clinicians prescribing for children must share in the blame.
Dr. Myron Yaster at Johns Hopkins University Hospital, Baltimore, has found that in a group of nearly 300 pediatric patients (average age, 11 years and average weight of 44 kg), overall the patients used only 42% of the prescribed amount of opioids. Almost half of the patients had a teenage sibling, a group that Dr. Yaster describes as the “target population of drug abuse.”
What’s going on here? Some of the problem dates back to the 1990s when physicians were urged to shift their focus toward the problem of inadequately treated pain. With the help of nurses armed with pain-rating schemes and smiley/grumpy face charts, the mantra became “no pain shall go unmedicated,” when the better response should have been “no pain shall go unmanaged.” But good pain management takes time. It requires that the physician and staff consider each patient as a unique individual. In many cases, reassurance and education can make a non–opioid medication or even no medication a better choice.
However, according to Dr. Yaster, “leftover medicine is the most important element in drug addiction.” Why did physicians prescribe 10 days of medication when his study revealed that most patients took the medication for only 5? It could just be a bad habit. Or it could be ignorance or inexperience. How many physicians ask at follow-up appointments “How long did you take your medication? Tell me the history of your pain.”
Or could it be that physicians are simply trying to prevent those annoying calls from patients who have run out of their medication? Dr. Yaster’s findings suggest that those calls would be few and far between. More careful thought into how much medication we prescribe also would mean that when a patient called for more medication that there was a problem. Either the patient’s recuperation has hit a worrisome bump in the road or possibly her medication is being diverted.
History tells us that physicians, even pediatricians, have been poor stewards of the powerful medications with which we have been entrusted. First, it was antibiotics and now opioids have joined the list.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].
To those of us who live and practice in the northeast, it comes as no surprise that the mortality rate for middle class whites is climbing. Obituaries in our local papers often include men and women in their forties “dying at home,” with no mention of cancer or chronic disease. Rarely, the family can bring itself to announce that their loved one has died of a drug overdose.
Deaths attributable to prescription opioid overdoses quadrupled in the decade from 1999 to 2010, and the trend shows little sign of abating as the number of prescriptions for opioids has risen tenfold over the last 20 years (“How Doctors Helped Drive the Addiction Crisis,” by Dr. Richard Friedman, New York Times, Nov. 7, 2015). Could physician behavior have contributed to outbreak of this deadly plague of addiction? That is like asking if something the zookeeper did or didn’t do could have been responsible for the escape of the man-eating tiger that is devouring the neighborhood children. Regardless of what other factors might be responsible for the epidemic of fatal prescription opioid overdoses, physicians must admit some culpability.
Until recently, I assumed that the problem of prescription opioids finding their way to addicts was unique to physicians treating adults. However, a study reported at the annual meeting of the American Society of Anesthesiologists reveals pediatricians and other clinicians prescribing for children must share in the blame.
Dr. Myron Yaster at Johns Hopkins University Hospital, Baltimore, has found that in a group of nearly 300 pediatric patients (average age, 11 years and average weight of 44 kg), overall the patients used only 42% of the prescribed amount of opioids. Almost half of the patients had a teenage sibling, a group that Dr. Yaster describes as the “target population of drug abuse.”
What’s going on here? Some of the problem dates back to the 1990s when physicians were urged to shift their focus toward the problem of inadequately treated pain. With the help of nurses armed with pain-rating schemes and smiley/grumpy face charts, the mantra became “no pain shall go unmedicated,” when the better response should have been “no pain shall go unmanaged.” But good pain management takes time. It requires that the physician and staff consider each patient as a unique individual. In many cases, reassurance and education can make a non–opioid medication or even no medication a better choice.
However, according to Dr. Yaster, “leftover medicine is the most important element in drug addiction.” Why did physicians prescribe 10 days of medication when his study revealed that most patients took the medication for only 5? It could just be a bad habit. Or it could be ignorance or inexperience. How many physicians ask at follow-up appointments “How long did you take your medication? Tell me the history of your pain.”
Or could it be that physicians are simply trying to prevent those annoying calls from patients who have run out of their medication? Dr. Yaster’s findings suggest that those calls would be few and far between. More careful thought into how much medication we prescribe also would mean that when a patient called for more medication that there was a problem. Either the patient’s recuperation has hit a worrisome bump in the road or possibly her medication is being diverted.
History tells us that physicians, even pediatricians, have been poor stewards of the powerful medications with which we have been entrusted. First, it was antibiotics and now opioids have joined the list.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.” Email him at [email protected].
Antidepressants highly effective against binge-eating disorder
People with binge-eating disorder have the greatest chance of achieving normal eating habits and alleviating symptoms associated with the disorder by taking second-generation antidepressants, topiramate, and lisdexamfetamine and engaging in cognitive-behavioral therapy, an analysis of several studies showed.
The findings should be used to “address other treatments, combinations of treatments, and comparisons between treatments; treatment for postbariatric surgery patients and children; and the course of these illnesses,” according to the report, released as part of the Comparative Effectiveness Review No. 160 by the Agency for Healthcare Research and Quality.
The authors of the report examined a total of 52 randomized controlled trials and 15 observational studies collected through searches of MEDLINE, EMBASE, the Cochrane Library, Academic OneFile, and the Cumulative Index to Nursing and Allied Health Literature databases, with 48 of the included studies specifically concerning binge-eating disorder (BED). English-language studies up through Jan. 19, 2015, were included for analysis, and the investigators specifically looked for studies of individuals who met DSM-IV or DSM-5 criteria for BED and studies of postbariatric surgery patients, including children, experiencing loss-of-control (LOC) eating habits.
Each study was evaluated based on a set of 15 “key questions” to determine the effectiveness and harms of the treatments involved. The key questions used by the investigators sought to determine the evidence of effectiveness and harms of BED treatments; LOC eating among bariatric surgery patients; and the effectiveness of any LOC treatments based on age, sex, race, ethnicity, initial body mass index, duration of illness, and coexisting conditions. In addition, similar questions were used to ascertain the effectiveness of treatments on pediatric patients.
“Broadly, we included pharmacological, psychological, behavioral, and combination interventions,” the report stated. “We considered physical and psychological health outcomes in four major categories: binge behavior (binge eating or LOC eating); binge-eating–related psychopathology (e.g., weight and shape concerns, dietary restraint); physical health functioning (i.e., weight and other indexes of metabolic health, e.g., diabetes); and general psychopathology (e.g., depression, anxiety).”
Antidepressants were found to be more effective than placebos across the studies included in the survey, specifically second-generation antidepressants, and were 1.67 times more likely to help BED patients achieve abstinence than placebos used in these trials; 41% of subjects receiving antidepressants ultimately achieved abstinence, compared with 23% on placebos.
With topiramate, binge eating generally decreased to as little as one episode per week, and a higher portion of subjects (58%) achieved abstinence than those on placebo (28%). In addition, topiramate was found to decrease “obsessive thoughts and compulsions related to binge eating” by nearly 30%, versus 23% in subjects taking placebos.
Studies involving lisdexamfetamine showed abstinence achieved in 40% of subjects, far higher than the 15% on placebos, and a likelihood of achieving abstinence 2.61 times higher than for those in the placebo cohorts. Binge-eating episodes per week also decreased, and were, on average, anywhere from 1.7 to 1.3 fewer than those in subjects taking placebo. Subjects receiving cognitive-behavioral therapy – whether led by a therapist or self-led, though the former was found to have stronger evidence of effectiveness than the latter – had an average of 2.3 fewer binge-eating episodes per week, and subjects involved with therapy were 4.95 times more likely to achieve abstinence than those who were not receiving therapy.
“Findings about BED treatment interventions are likely to be applicable to all adults age 18 and older with the disorder, but chiefly to overweight or obese women,” the report stated. “We cannot comment on the applicability of treatment findings for specific subgroups of adults (even among women) or whether findings extend to BED patients diagnosed based on DSM-5 criteria.”
The authors also noted that the findings are unclear with respect to adolescents with BED or members of ethnic groups, and children with loss-of-control eating or who have undergone bariatric surgery.
“A convention for reporting and analyzing” outcomes is necessary for the findings of this study to take on real-world applications that can be beneficial to clinicians and their patients in the near future, the authors concluded. However, more multisite randomized, controlled trials are needed.
People with binge-eating disorder have the greatest chance of achieving normal eating habits and alleviating symptoms associated with the disorder by taking second-generation antidepressants, topiramate, and lisdexamfetamine and engaging in cognitive-behavioral therapy, an analysis of several studies showed.
The findings should be used to “address other treatments, combinations of treatments, and comparisons between treatments; treatment for postbariatric surgery patients and children; and the course of these illnesses,” according to the report, released as part of the Comparative Effectiveness Review No. 160 by the Agency for Healthcare Research and Quality.
The authors of the report examined a total of 52 randomized controlled trials and 15 observational studies collected through searches of MEDLINE, EMBASE, the Cochrane Library, Academic OneFile, and the Cumulative Index to Nursing and Allied Health Literature databases, with 48 of the included studies specifically concerning binge-eating disorder (BED). English-language studies up through Jan. 19, 2015, were included for analysis, and the investigators specifically looked for studies of individuals who met DSM-IV or DSM-5 criteria for BED and studies of postbariatric surgery patients, including children, experiencing loss-of-control (LOC) eating habits.
Each study was evaluated based on a set of 15 “key questions” to determine the effectiveness and harms of the treatments involved. The key questions used by the investigators sought to determine the evidence of effectiveness and harms of BED treatments; LOC eating among bariatric surgery patients; and the effectiveness of any LOC treatments based on age, sex, race, ethnicity, initial body mass index, duration of illness, and coexisting conditions. In addition, similar questions were used to ascertain the effectiveness of treatments on pediatric patients.
“Broadly, we included pharmacological, psychological, behavioral, and combination interventions,” the report stated. “We considered physical and psychological health outcomes in four major categories: binge behavior (binge eating or LOC eating); binge-eating–related psychopathology (e.g., weight and shape concerns, dietary restraint); physical health functioning (i.e., weight and other indexes of metabolic health, e.g., diabetes); and general psychopathology (e.g., depression, anxiety).”
Antidepressants were found to be more effective than placebos across the studies included in the survey, specifically second-generation antidepressants, and were 1.67 times more likely to help BED patients achieve abstinence than placebos used in these trials; 41% of subjects receiving antidepressants ultimately achieved abstinence, compared with 23% on placebos.
With topiramate, binge eating generally decreased to as little as one episode per week, and a higher portion of subjects (58%) achieved abstinence than those on placebo (28%). In addition, topiramate was found to decrease “obsessive thoughts and compulsions related to binge eating” by nearly 30%, versus 23% in subjects taking placebos.
Studies involving lisdexamfetamine showed abstinence achieved in 40% of subjects, far higher than the 15% on placebos, and a likelihood of achieving abstinence 2.61 times higher than for those in the placebo cohorts. Binge-eating episodes per week also decreased, and were, on average, anywhere from 1.7 to 1.3 fewer than those in subjects taking placebo. Subjects receiving cognitive-behavioral therapy – whether led by a therapist or self-led, though the former was found to have stronger evidence of effectiveness than the latter – had an average of 2.3 fewer binge-eating episodes per week, and subjects involved with therapy were 4.95 times more likely to achieve abstinence than those who were not receiving therapy.
“Findings about BED treatment interventions are likely to be applicable to all adults age 18 and older with the disorder, but chiefly to overweight or obese women,” the report stated. “We cannot comment on the applicability of treatment findings for specific subgroups of adults (even among women) or whether findings extend to BED patients diagnosed based on DSM-5 criteria.”
The authors also noted that the findings are unclear with respect to adolescents with BED or members of ethnic groups, and children with loss-of-control eating or who have undergone bariatric surgery.
“A convention for reporting and analyzing” outcomes is necessary for the findings of this study to take on real-world applications that can be beneficial to clinicians and their patients in the near future, the authors concluded. However, more multisite randomized, controlled trials are needed.
People with binge-eating disorder have the greatest chance of achieving normal eating habits and alleviating symptoms associated with the disorder by taking second-generation antidepressants, topiramate, and lisdexamfetamine and engaging in cognitive-behavioral therapy, an analysis of several studies showed.
The findings should be used to “address other treatments, combinations of treatments, and comparisons between treatments; treatment for postbariatric surgery patients and children; and the course of these illnesses,” according to the report, released as part of the Comparative Effectiveness Review No. 160 by the Agency for Healthcare Research and Quality.
The authors of the report examined a total of 52 randomized controlled trials and 15 observational studies collected through searches of MEDLINE, EMBASE, the Cochrane Library, Academic OneFile, and the Cumulative Index to Nursing and Allied Health Literature databases, with 48 of the included studies specifically concerning binge-eating disorder (BED). English-language studies up through Jan. 19, 2015, were included for analysis, and the investigators specifically looked for studies of individuals who met DSM-IV or DSM-5 criteria for BED and studies of postbariatric surgery patients, including children, experiencing loss-of-control (LOC) eating habits.
Each study was evaluated based on a set of 15 “key questions” to determine the effectiveness and harms of the treatments involved. The key questions used by the investigators sought to determine the evidence of effectiveness and harms of BED treatments; LOC eating among bariatric surgery patients; and the effectiveness of any LOC treatments based on age, sex, race, ethnicity, initial body mass index, duration of illness, and coexisting conditions. In addition, similar questions were used to ascertain the effectiveness of treatments on pediatric patients.
“Broadly, we included pharmacological, psychological, behavioral, and combination interventions,” the report stated. “We considered physical and psychological health outcomes in four major categories: binge behavior (binge eating or LOC eating); binge-eating–related psychopathology (e.g., weight and shape concerns, dietary restraint); physical health functioning (i.e., weight and other indexes of metabolic health, e.g., diabetes); and general psychopathology (e.g., depression, anxiety).”
Antidepressants were found to be more effective than placebos across the studies included in the survey, specifically second-generation antidepressants, and were 1.67 times more likely to help BED patients achieve abstinence than placebos used in these trials; 41% of subjects receiving antidepressants ultimately achieved abstinence, compared with 23% on placebos.
With topiramate, binge eating generally decreased to as little as one episode per week, and a higher portion of subjects (58%) achieved abstinence than those on placebo (28%). In addition, topiramate was found to decrease “obsessive thoughts and compulsions related to binge eating” by nearly 30%, versus 23% in subjects taking placebos.
Studies involving lisdexamfetamine showed abstinence achieved in 40% of subjects, far higher than the 15% on placebos, and a likelihood of achieving abstinence 2.61 times higher than for those in the placebo cohorts. Binge-eating episodes per week also decreased, and were, on average, anywhere from 1.7 to 1.3 fewer than those in subjects taking placebo. Subjects receiving cognitive-behavioral therapy – whether led by a therapist or self-led, though the former was found to have stronger evidence of effectiveness than the latter – had an average of 2.3 fewer binge-eating episodes per week, and subjects involved with therapy were 4.95 times more likely to achieve abstinence than those who were not receiving therapy.
“Findings about BED treatment interventions are likely to be applicable to all adults age 18 and older with the disorder, but chiefly to overweight or obese women,” the report stated. “We cannot comment on the applicability of treatment findings for specific subgroups of adults (even among women) or whether findings extend to BED patients diagnosed based on DSM-5 criteria.”
The authors also noted that the findings are unclear with respect to adolescents with BED or members of ethnic groups, and children with loss-of-control eating or who have undergone bariatric surgery.
“A convention for reporting and analyzing” outcomes is necessary for the findings of this study to take on real-world applications that can be beneficial to clinicians and their patients in the near future, the authors concluded. However, more multisite randomized, controlled trials are needed.
Prior authorization sausage factory turns approvals into denials
“We are just statistics, born to consume resources.” –Horace
You know the winter is coming when rheumatologists spend their weekends writing appeal letters for sildenafil.
I inherited a scleroderma patient from a retired colleague. She has had severe Raynaud’s for which she’d been on sildenafil since 2013. On Nov. 23, 2015, I received a letter stating that the medication would no longer be covered because the patient did not meet criteria (in this case, pulmonary arterial hypertension).
I had to submit a letter of appeal, in which I explained how, despite maximum tolerated doses of nifedipine and pentoxifylline, she continued to have digital ischemia, and how, when she finally started the sildenafil, which they had approved prior, the problem went away. I continued to say:
“In the medical literature on this problem, the PDE-5 inhibitors, of which sildenafil is one, is typically recommended, after vasodilation, on the basis of Level I evidence (that is, evidence from high quality randomized controlled trials). Sildenafil has been shown to promote complete healing of digital ulcers and prevents the formation of new ulcers. Thought leaders in the field uniformly recommend this drug as an important part of therapy particularly in patients who have already had digital ulcers. I am happy to provide you with the literature upon request.
“I urge you to reconsider your decision. If you withhold this drug there is a chance that the patient will end up with ulcers again and this could potentially cost you even more. Not only would it impair the patient’s ability to work, which leads to loss of income for her, it would also cost you more in terms of paying for her health care.”
On Nov. 28, I received a second denial, no different than the first letter: “Your request was reviewed by a Medical Doctor specialized in Internal Medicine/Rheumatology. Upon review of the available information, it was determined that the previous decision should be upheld because the Prior Authorization criteria is not met. This determination was made based upon our review of your health condition in relation to the prior authorization criteria and/or guidelines listed below. You have CREST ... with Raynaud’s phenomenon which is not a covered diagnosis. You do not have Pulmonary Arterial Hypertension. Therefore the requested drug sildenafil citrate is not medically necessary according to plan criteria. The denial is therefore appropriate and consistent with your benefits.
“Sildenafil will be approved based on one of the following criteria:
(1) All of the following:
(A) Pulmonary arterial hypertension is symptomatic; AND
(B) Submission of medical records documenting diagnosis of pulmonary arterial hypertension that is confirmed by right heart catheterization; OR
(2) Patient is currently on any therapy for the diagnosis of pulmonary arterial hypertension.”
On Dec. 4, I fired off the following response:
“I received your decision letter dated 11/28/2015 in which you reiterate that your criteria for approval requires a diagnosis of pulmonary hypertension, as if you had not read my first letter at all. This request is not for pulmonary hypertension, it is to prevent limb-threatening gangrene and ischemia from Raynaud’s phenomenon. Please reconsider your decision. We do not want this young patient to lose any digits.”
It’s quite ironic that on the same weekend that I wrote my first letter, a mentor and friend of mine who is a rheumatologist also wrote a letter of appeal to get a prescription for sildenafil approved for a scleroderma patient with Raynaud’s who failed previous medications. She got sildenafil approved. At her suggestion, I attached a copy of the 2005 study published in Circulation demonstrating the efficacy of sildenafil for Raynaud’s to support my letter after the second denial (Circulation. 2005 Nov 8;112[19]:2980-5). As of this writing, I still have not heard back.
Dr. Chan practices rheumatology in Pawtucket, R.I.
“We are just statistics, born to consume resources.” –Horace
You know the winter is coming when rheumatologists spend their weekends writing appeal letters for sildenafil.
I inherited a scleroderma patient from a retired colleague. She has had severe Raynaud’s for which she’d been on sildenafil since 2013. On Nov. 23, 2015, I received a letter stating that the medication would no longer be covered because the patient did not meet criteria (in this case, pulmonary arterial hypertension).
I had to submit a letter of appeal, in which I explained how, despite maximum tolerated doses of nifedipine and pentoxifylline, she continued to have digital ischemia, and how, when she finally started the sildenafil, which they had approved prior, the problem went away. I continued to say:
“In the medical literature on this problem, the PDE-5 inhibitors, of which sildenafil is one, is typically recommended, after vasodilation, on the basis of Level I evidence (that is, evidence from high quality randomized controlled trials). Sildenafil has been shown to promote complete healing of digital ulcers and prevents the formation of new ulcers. Thought leaders in the field uniformly recommend this drug as an important part of therapy particularly in patients who have already had digital ulcers. I am happy to provide you with the literature upon request.
“I urge you to reconsider your decision. If you withhold this drug there is a chance that the patient will end up with ulcers again and this could potentially cost you even more. Not only would it impair the patient’s ability to work, which leads to loss of income for her, it would also cost you more in terms of paying for her health care.”
On Nov. 28, I received a second denial, no different than the first letter: “Your request was reviewed by a Medical Doctor specialized in Internal Medicine/Rheumatology. Upon review of the available information, it was determined that the previous decision should be upheld because the Prior Authorization criteria is not met. This determination was made based upon our review of your health condition in relation to the prior authorization criteria and/or guidelines listed below. You have CREST ... with Raynaud’s phenomenon which is not a covered diagnosis. You do not have Pulmonary Arterial Hypertension. Therefore the requested drug sildenafil citrate is not medically necessary according to plan criteria. The denial is therefore appropriate and consistent with your benefits.
“Sildenafil will be approved based on one of the following criteria:
(1) All of the following:
(A) Pulmonary arterial hypertension is symptomatic; AND
(B) Submission of medical records documenting diagnosis of pulmonary arterial hypertension that is confirmed by right heart catheterization; OR
(2) Patient is currently on any therapy for the diagnosis of pulmonary arterial hypertension.”
On Dec. 4, I fired off the following response:
“I received your decision letter dated 11/28/2015 in which you reiterate that your criteria for approval requires a diagnosis of pulmonary hypertension, as if you had not read my first letter at all. This request is not for pulmonary hypertension, it is to prevent limb-threatening gangrene and ischemia from Raynaud’s phenomenon. Please reconsider your decision. We do not want this young patient to lose any digits.”
It’s quite ironic that on the same weekend that I wrote my first letter, a mentor and friend of mine who is a rheumatologist also wrote a letter of appeal to get a prescription for sildenafil approved for a scleroderma patient with Raynaud’s who failed previous medications. She got sildenafil approved. At her suggestion, I attached a copy of the 2005 study published in Circulation demonstrating the efficacy of sildenafil for Raynaud’s to support my letter after the second denial (Circulation. 2005 Nov 8;112[19]:2980-5). As of this writing, I still have not heard back.
Dr. Chan practices rheumatology in Pawtucket, R.I.
“We are just statistics, born to consume resources.” –Horace
You know the winter is coming when rheumatologists spend their weekends writing appeal letters for sildenafil.
I inherited a scleroderma patient from a retired colleague. She has had severe Raynaud’s for which she’d been on sildenafil since 2013. On Nov. 23, 2015, I received a letter stating that the medication would no longer be covered because the patient did not meet criteria (in this case, pulmonary arterial hypertension).
I had to submit a letter of appeal, in which I explained how, despite maximum tolerated doses of nifedipine and pentoxifylline, she continued to have digital ischemia, and how, when she finally started the sildenafil, which they had approved prior, the problem went away. I continued to say:
“In the medical literature on this problem, the PDE-5 inhibitors, of which sildenafil is one, is typically recommended, after vasodilation, on the basis of Level I evidence (that is, evidence from high quality randomized controlled trials). Sildenafil has been shown to promote complete healing of digital ulcers and prevents the formation of new ulcers. Thought leaders in the field uniformly recommend this drug as an important part of therapy particularly in patients who have already had digital ulcers. I am happy to provide you with the literature upon request.
“I urge you to reconsider your decision. If you withhold this drug there is a chance that the patient will end up with ulcers again and this could potentially cost you even more. Not only would it impair the patient’s ability to work, which leads to loss of income for her, it would also cost you more in terms of paying for her health care.”
On Nov. 28, I received a second denial, no different than the first letter: “Your request was reviewed by a Medical Doctor specialized in Internal Medicine/Rheumatology. Upon review of the available information, it was determined that the previous decision should be upheld because the Prior Authorization criteria is not met. This determination was made based upon our review of your health condition in relation to the prior authorization criteria and/or guidelines listed below. You have CREST ... with Raynaud’s phenomenon which is not a covered diagnosis. You do not have Pulmonary Arterial Hypertension. Therefore the requested drug sildenafil citrate is not medically necessary according to plan criteria. The denial is therefore appropriate and consistent with your benefits.
“Sildenafil will be approved based on one of the following criteria:
(1) All of the following:
(A) Pulmonary arterial hypertension is symptomatic; AND
(B) Submission of medical records documenting diagnosis of pulmonary arterial hypertension that is confirmed by right heart catheterization; OR
(2) Patient is currently on any therapy for the diagnosis of pulmonary arterial hypertension.”
On Dec. 4, I fired off the following response:
“I received your decision letter dated 11/28/2015 in which you reiterate that your criteria for approval requires a diagnosis of pulmonary hypertension, as if you had not read my first letter at all. This request is not for pulmonary hypertension, it is to prevent limb-threatening gangrene and ischemia from Raynaud’s phenomenon. Please reconsider your decision. We do not want this young patient to lose any digits.”
It’s quite ironic that on the same weekend that I wrote my first letter, a mentor and friend of mine who is a rheumatologist also wrote a letter of appeal to get a prescription for sildenafil approved for a scleroderma patient with Raynaud’s who failed previous medications. She got sildenafil approved. At her suggestion, I attached a copy of the 2005 study published in Circulation demonstrating the efficacy of sildenafil for Raynaud’s to support my letter after the second denial (Circulation. 2005 Nov 8;112[19]:2980-5). As of this writing, I still have not heard back.
Dr. Chan practices rheumatology in Pawtucket, R.I.
Few teen females prescribed teratogenic meds get contraceptive advice, Rx
Fewer than one-third of adolescent females prescribed a teratogenic medication were counseled about, prescribed, or referred for contraception, according to a retrospective review of data from a single academic pediatric medical center.
The records from 1,694 female patients aged 14-25 years, who received 4,506 medications of Food and Drug Administration pregnancy risk category D or X – mostly commonly topiramate, methotrexate, diazepam, isotretinoin, or enalapril – showed that contraceptive counseling, prescription, or referral occurred in 29% of visits, according to a paper published online Dec. 16 in Pediatrics.
White females were 61% more likely to receive contraceptive provision than were nonwhites, and girls aged 16 years or older were 20% more likely to receive it than were girls aged 14-15 years (Pediatrics 2016, Jan. doi: 10.1542/peds.2015-1454).
Teratogens with a federal surveillance system, such as iPLEDGE or REMS, were associated with twofold increase in the rate of contraceptive provision, but a much lower likelihood of documentation of menstrual and sexual histories.
“This finding was unexpected given that the focus of these systems is to proactively reduce the risk of unplanned pregnancy during drug treatment,” wrote Stephani L. Stancil of Children’s Mercy Hospital, Kansas City, Mo., and coauthors.
“Opportunity exists in these adolescents to increase rates of contraceptive counsel, the prescription of contraception if appropriate, or referral for such care when it becomes necessary to use a medication with known teratogenic potential,” they said.
Children’s Mercy Hospital supported the study. No conflicts of interest were declared.
“Even if a provider does not think it is within his or her scope of care to provide a contraceptive method, asking the questions to assess whether a contraceptive method might be needed from another provider is essential.
“In addition, all providers should be aware of the newer recommendation that all adolescents should be offered the option of a long-acting reversible contraceptive method to prevent pregnancy.
The fact that the Affordable Care Act allows us to provide 18 different contraceptive methods without any cost sharing to the patient should also make adolescent pregnancy prevention easier than ever.”
Erica J. Gibson, M.D., is an expert in adolescent medicine in the department of pediatrics at the University of Vermont Children’s Hospital, Burlington. Her remarks are excerpted from an article published in Pediatrics (2016, Jan. doi:10.1542/peds.2015-3826). She disclosed no conflicts of interest.
“Even if a provider does not think it is within his or her scope of care to provide a contraceptive method, asking the questions to assess whether a contraceptive method might be needed from another provider is essential.
“In addition, all providers should be aware of the newer recommendation that all adolescents should be offered the option of a long-acting reversible contraceptive method to prevent pregnancy.
The fact that the Affordable Care Act allows us to provide 18 different contraceptive methods without any cost sharing to the patient should also make adolescent pregnancy prevention easier than ever.”
Erica J. Gibson, M.D., is an expert in adolescent medicine in the department of pediatrics at the University of Vermont Children’s Hospital, Burlington. Her remarks are excerpted from an article published in Pediatrics (2016, Jan. doi:10.1542/peds.2015-3826). She disclosed no conflicts of interest.
“Even if a provider does not think it is within his or her scope of care to provide a contraceptive method, asking the questions to assess whether a contraceptive method might be needed from another provider is essential.
“In addition, all providers should be aware of the newer recommendation that all adolescents should be offered the option of a long-acting reversible contraceptive method to prevent pregnancy.
The fact that the Affordable Care Act allows us to provide 18 different contraceptive methods without any cost sharing to the patient should also make adolescent pregnancy prevention easier than ever.”
Erica J. Gibson, M.D., is an expert in adolescent medicine in the department of pediatrics at the University of Vermont Children’s Hospital, Burlington. Her remarks are excerpted from an article published in Pediatrics (2016, Jan. doi:10.1542/peds.2015-3826). She disclosed no conflicts of interest.
Fewer than one-third of adolescent females prescribed a teratogenic medication were counseled about, prescribed, or referred for contraception, according to a retrospective review of data from a single academic pediatric medical center.
The records from 1,694 female patients aged 14-25 years, who received 4,506 medications of Food and Drug Administration pregnancy risk category D or X – mostly commonly topiramate, methotrexate, diazepam, isotretinoin, or enalapril – showed that contraceptive counseling, prescription, or referral occurred in 29% of visits, according to a paper published online Dec. 16 in Pediatrics.
White females were 61% more likely to receive contraceptive provision than were nonwhites, and girls aged 16 years or older were 20% more likely to receive it than were girls aged 14-15 years (Pediatrics 2016, Jan. doi: 10.1542/peds.2015-1454).
Teratogens with a federal surveillance system, such as iPLEDGE or REMS, were associated with twofold increase in the rate of contraceptive provision, but a much lower likelihood of documentation of menstrual and sexual histories.
“This finding was unexpected given that the focus of these systems is to proactively reduce the risk of unplanned pregnancy during drug treatment,” wrote Stephani L. Stancil of Children’s Mercy Hospital, Kansas City, Mo., and coauthors.
“Opportunity exists in these adolescents to increase rates of contraceptive counsel, the prescription of contraception if appropriate, or referral for such care when it becomes necessary to use a medication with known teratogenic potential,” they said.
Children’s Mercy Hospital supported the study. No conflicts of interest were declared.
Fewer than one-third of adolescent females prescribed a teratogenic medication were counseled about, prescribed, or referred for contraception, according to a retrospective review of data from a single academic pediatric medical center.
The records from 1,694 female patients aged 14-25 years, who received 4,506 medications of Food and Drug Administration pregnancy risk category D or X – mostly commonly topiramate, methotrexate, diazepam, isotretinoin, or enalapril – showed that contraceptive counseling, prescription, or referral occurred in 29% of visits, according to a paper published online Dec. 16 in Pediatrics.
White females were 61% more likely to receive contraceptive provision than were nonwhites, and girls aged 16 years or older were 20% more likely to receive it than were girls aged 14-15 years (Pediatrics 2016, Jan. doi: 10.1542/peds.2015-1454).
Teratogens with a federal surveillance system, such as iPLEDGE or REMS, were associated with twofold increase in the rate of contraceptive provision, but a much lower likelihood of documentation of menstrual and sexual histories.
“This finding was unexpected given that the focus of these systems is to proactively reduce the risk of unplanned pregnancy during drug treatment,” wrote Stephani L. Stancil of Children’s Mercy Hospital, Kansas City, Mo., and coauthors.
“Opportunity exists in these adolescents to increase rates of contraceptive counsel, the prescription of contraception if appropriate, or referral for such care when it becomes necessary to use a medication with known teratogenic potential,” they said.
Children’s Mercy Hospital supported the study. No conflicts of interest were declared.
FROM PEDIATRICS
Key clinical point: Fewer than one-third of adolescent females prescribed a teratogenic medication also receive contraception provision.
Major finding: Among adolescent females prescribed a known teratogen, contraception provision occurred in 29% of visits.
Data source: A single-center, retrospective study of 1,694 female patients aged 14-25 years, prescribed a medication of FDA pregnancy risk category D or X.
Disclosures: Children’s Mercy Hospital, Kansas City, supported the study. No conflicts of interest were declared.
ACC, AHA update performance measures for lipid management
Updated performance measures regarding lipid management for secondary prevention, introducing and placing great emphasis on shared decision making between clinicians and patients, have been released jointly by the American College of Cardiology and the American Heart Association.
“These measures respect the wishes of patients regarding the use of statins and do not penalize physicians who may have a patient decline to take the medications for personal reasons,” Dr. Joseph P. Drozda Jr., chair of the update’s writing committee, said in a statement accompanying the release.
“Integrating patient values, preferences, and personal context with evidence-based medicine and guidelines is novel and changes the focus from recommending and prescribing statins ... to promoting choice by an informed patient,” said Dr. Drozda, director of outcomes research at Mercy Health, St. Louis.
Performance measures are intended to accelerate the translation of scientific evidence into clinical practice, and they are rapidly updated whenever there are changes to a relevant ACC/AHA guideline. In this case, lipid management performance measures needed updating because of new recommendations in the most recent ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (Circulation. 2014 Jun 24;129[25 Suppl 2]:S1-45). The new recommendations emphasized treatment with high-intensity statin therapy instead of achieving LDL-cholesterol targets.
In accordance with that, the lipid performance measures have been revised in four areas of lipid management: in secondary prevention for patients who have peripheral artery disease, STEMI or non-STEMI myocardial infarction, percutaneous coronary intervention, and coronary artery disease/hypertension. In addition, a new performance measure has been added addressing clinical atherosclerotic cardiovascular disease.
Abundant research has shown that only a fraction of patients with peripheral artery disease, MI, percutaneous coronary intervention, and coronary artery disease/hypertension who would benefit greatly from statin therapy are actually taking it, and that those who do take statins generally are receiving suboptimal doses. Studies also have clearly demonstrated that more intensive statin regimens reduce adverse cardiovascular events even further in these patient populations, Dr. Drozda and his associates said (J Am Coll Cardiol. 2015 Dec 13 [doi:10.1016/j.jacc.2015.02.003]).
“Better patient outcomes are realized only if patients agree with, act on, and adhere to [statin recommendations] for 5-10 years.” At present, up to half of patients prescribed statins for secondary prevention discontinue the drugs within 1-2 years, they noted.
“Clinicians need to embrace the concept that evidence-based medicine and guidelines alone are not sufficient to make a [treatment] recommendation or a decision; rather, the evidence has to be considered from the viewpoint of what matters to individual patients. Hence, the clinical encounter transforms from one where the clinician strives to convince the patient of the ‘right answer’ to one where the clinician and patient collaborate, deliberate, and arrive at the ‘best answer’ that fits patient preferences, values, and context,” Dr. Drozda and his associates said.
Clinicians may not be aware of all the factors contributing to statin discontinuation and missed doses. The cost of the drug or the copay amount may be unaffordable. The label instructions may be unclear. The patient may be too forgetful to take medications reliably, or too embarrassed to discuss the agent’s adverse effects. The patient may dislike having to take any medication, or may not understand its importance when he or she has no symptoms. One strategy to address all possible reasons for nonadherence and to accomplish shared decision making is for the clinician at every office visit to review the medication list; ask about adverse effects, cost, and adherence; and discuss barriers to adherence, the investigators said.
The updated lipid performance measures are available at www.acc.org and www.my.americanheart.org.
This work was supported exclusively by the ACC and the AHA. The financial disclosures of Dr. Drozda and the other members of the writing committee are available from the ACC and the AHA.
Updated performance measures regarding lipid management for secondary prevention, introducing and placing great emphasis on shared decision making between clinicians and patients, have been released jointly by the American College of Cardiology and the American Heart Association.
“These measures respect the wishes of patients regarding the use of statins and do not penalize physicians who may have a patient decline to take the medications for personal reasons,” Dr. Joseph P. Drozda Jr., chair of the update’s writing committee, said in a statement accompanying the release.
“Integrating patient values, preferences, and personal context with evidence-based medicine and guidelines is novel and changes the focus from recommending and prescribing statins ... to promoting choice by an informed patient,” said Dr. Drozda, director of outcomes research at Mercy Health, St. Louis.
Performance measures are intended to accelerate the translation of scientific evidence into clinical practice, and they are rapidly updated whenever there are changes to a relevant ACC/AHA guideline. In this case, lipid management performance measures needed updating because of new recommendations in the most recent ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (Circulation. 2014 Jun 24;129[25 Suppl 2]:S1-45). The new recommendations emphasized treatment with high-intensity statin therapy instead of achieving LDL-cholesterol targets.
In accordance with that, the lipid performance measures have been revised in four areas of lipid management: in secondary prevention for patients who have peripheral artery disease, STEMI or non-STEMI myocardial infarction, percutaneous coronary intervention, and coronary artery disease/hypertension. In addition, a new performance measure has been added addressing clinical atherosclerotic cardiovascular disease.
Abundant research has shown that only a fraction of patients with peripheral artery disease, MI, percutaneous coronary intervention, and coronary artery disease/hypertension who would benefit greatly from statin therapy are actually taking it, and that those who do take statins generally are receiving suboptimal doses. Studies also have clearly demonstrated that more intensive statin regimens reduce adverse cardiovascular events even further in these patient populations, Dr. Drozda and his associates said (J Am Coll Cardiol. 2015 Dec 13 [doi:10.1016/j.jacc.2015.02.003]).
“Better patient outcomes are realized only if patients agree with, act on, and adhere to [statin recommendations] for 5-10 years.” At present, up to half of patients prescribed statins for secondary prevention discontinue the drugs within 1-2 years, they noted.
“Clinicians need to embrace the concept that evidence-based medicine and guidelines alone are not sufficient to make a [treatment] recommendation or a decision; rather, the evidence has to be considered from the viewpoint of what matters to individual patients. Hence, the clinical encounter transforms from one where the clinician strives to convince the patient of the ‘right answer’ to one where the clinician and patient collaborate, deliberate, and arrive at the ‘best answer’ that fits patient preferences, values, and context,” Dr. Drozda and his associates said.
Clinicians may not be aware of all the factors contributing to statin discontinuation and missed doses. The cost of the drug or the copay amount may be unaffordable. The label instructions may be unclear. The patient may be too forgetful to take medications reliably, or too embarrassed to discuss the agent’s adverse effects. The patient may dislike having to take any medication, or may not understand its importance when he or she has no symptoms. One strategy to address all possible reasons for nonadherence and to accomplish shared decision making is for the clinician at every office visit to review the medication list; ask about adverse effects, cost, and adherence; and discuss barriers to adherence, the investigators said.
The updated lipid performance measures are available at www.acc.org and www.my.americanheart.org.
This work was supported exclusively by the ACC and the AHA. The financial disclosures of Dr. Drozda and the other members of the writing committee are available from the ACC and the AHA.
Updated performance measures regarding lipid management for secondary prevention, introducing and placing great emphasis on shared decision making between clinicians and patients, have been released jointly by the American College of Cardiology and the American Heart Association.
“These measures respect the wishes of patients regarding the use of statins and do not penalize physicians who may have a patient decline to take the medications for personal reasons,” Dr. Joseph P. Drozda Jr., chair of the update’s writing committee, said in a statement accompanying the release.
“Integrating patient values, preferences, and personal context with evidence-based medicine and guidelines is novel and changes the focus from recommending and prescribing statins ... to promoting choice by an informed patient,” said Dr. Drozda, director of outcomes research at Mercy Health, St. Louis.
Performance measures are intended to accelerate the translation of scientific evidence into clinical practice, and they are rapidly updated whenever there are changes to a relevant ACC/AHA guideline. In this case, lipid management performance measures needed updating because of new recommendations in the most recent ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (Circulation. 2014 Jun 24;129[25 Suppl 2]:S1-45). The new recommendations emphasized treatment with high-intensity statin therapy instead of achieving LDL-cholesterol targets.
In accordance with that, the lipid performance measures have been revised in four areas of lipid management: in secondary prevention for patients who have peripheral artery disease, STEMI or non-STEMI myocardial infarction, percutaneous coronary intervention, and coronary artery disease/hypertension. In addition, a new performance measure has been added addressing clinical atherosclerotic cardiovascular disease.
Abundant research has shown that only a fraction of patients with peripheral artery disease, MI, percutaneous coronary intervention, and coronary artery disease/hypertension who would benefit greatly from statin therapy are actually taking it, and that those who do take statins generally are receiving suboptimal doses. Studies also have clearly demonstrated that more intensive statin regimens reduce adverse cardiovascular events even further in these patient populations, Dr. Drozda and his associates said (J Am Coll Cardiol. 2015 Dec 13 [doi:10.1016/j.jacc.2015.02.003]).
“Better patient outcomes are realized only if patients agree with, act on, and adhere to [statin recommendations] for 5-10 years.” At present, up to half of patients prescribed statins for secondary prevention discontinue the drugs within 1-2 years, they noted.
“Clinicians need to embrace the concept that evidence-based medicine and guidelines alone are not sufficient to make a [treatment] recommendation or a decision; rather, the evidence has to be considered from the viewpoint of what matters to individual patients. Hence, the clinical encounter transforms from one where the clinician strives to convince the patient of the ‘right answer’ to one where the clinician and patient collaborate, deliberate, and arrive at the ‘best answer’ that fits patient preferences, values, and context,” Dr. Drozda and his associates said.
Clinicians may not be aware of all the factors contributing to statin discontinuation and missed doses. The cost of the drug or the copay amount may be unaffordable. The label instructions may be unclear. The patient may be too forgetful to take medications reliably, or too embarrassed to discuss the agent’s adverse effects. The patient may dislike having to take any medication, or may not understand its importance when he or she has no symptoms. One strategy to address all possible reasons for nonadherence and to accomplish shared decision making is for the clinician at every office visit to review the medication list; ask about adverse effects, cost, and adherence; and discuss barriers to adherence, the investigators said.
The updated lipid performance measures are available at www.acc.org and www.my.americanheart.org.
This work was supported exclusively by the ACC and the AHA. The financial disclosures of Dr. Drozda and the other members of the writing committee are available from the ACC and the AHA.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Sugammadex OK’d to reverse neuromuscular blockade during surgery
The Food and Drug Administration approved on Dec. 15 Merck’s sugammadex (Bridion) injection to reverse the effects of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide during surgery.
The safety and efficacy of sugammadex were evaluated in three phase III trials involving 456 participants; most recovered within 5 minutes. An FDA review of the drug found that there was less residual neuromuscular blockade with sugammadex compared to neostigmine, and a 4-minute time savings to extubation and operating room discharge.
“Bridion provides a new treatment option that may help patients recover sooner from medications used for intubation or ventilation during surgery. This drug enables medical personnel to reverse the effects of neuromuscular blocking drugs and restore spontaneous breathing after surgery,” Dr. Sharon Hertz, director of the FDA’s Division of Anesthesia, Analgesia, and Addiction Products, said in a statement.
Although approved in other countries, sugammadex has been in the FDA’s review process since 2007, previously rejected and held up by concerns over anaphylaxis and other issues.
Because of that, sugammadex was further evaluated in a randomized, double-blind, parallel-group, repeat-dose trial. Of the 299 participants treated with Bridion, one person had an anaphylactic reaction. “Clinicians should be aware of the possibility of a hypersensitivity reaction or anaphylaxis and should intervene as appropriate,” the agency said in its statement.
Cases of marked bradycardia, some of which have resulted in cardiac arrest, have also been observed within minutes after the administration of Bridion. Tachycardia and bradycardia have been associated with cases of anaphylaxis. “Patients should be closely monitored for hemodynamic changes during and after reversal of neuromuscular blockade, and treatment with anticholinergic agents, such as atropine, should be administered if clinically significant bradycardia is observed,” the agency said.
The most common side effects reported in trials were vomiting, hypotension, pain, headache, and nausea. “Doctors should also advise women using hormonal contraceptives that Bridion may temporarily reduce the contraceptive effect so they must use an alternate method of birth control for a period of time,” the agency said.
Rocuronium bromide and vecuronium bromide are used to paralyze the vocal cords for tracheal intubation, as well as to paralyze patients under general anesthesia and prevent spontaneous breathing during ventilation. Sugammadex is a new molecular entity of the gamma-cyclodextrin class, designed to bind rocuronium and vecuronium.
The Food and Drug Administration approved on Dec. 15 Merck’s sugammadex (Bridion) injection to reverse the effects of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide during surgery.
The safety and efficacy of sugammadex were evaluated in three phase III trials involving 456 participants; most recovered within 5 minutes. An FDA review of the drug found that there was less residual neuromuscular blockade with sugammadex compared to neostigmine, and a 4-minute time savings to extubation and operating room discharge.
“Bridion provides a new treatment option that may help patients recover sooner from medications used for intubation or ventilation during surgery. This drug enables medical personnel to reverse the effects of neuromuscular blocking drugs and restore spontaneous breathing after surgery,” Dr. Sharon Hertz, director of the FDA’s Division of Anesthesia, Analgesia, and Addiction Products, said in a statement.
Although approved in other countries, sugammadex has been in the FDA’s review process since 2007, previously rejected and held up by concerns over anaphylaxis and other issues.
Because of that, sugammadex was further evaluated in a randomized, double-blind, parallel-group, repeat-dose trial. Of the 299 participants treated with Bridion, one person had an anaphylactic reaction. “Clinicians should be aware of the possibility of a hypersensitivity reaction or anaphylaxis and should intervene as appropriate,” the agency said in its statement.
Cases of marked bradycardia, some of which have resulted in cardiac arrest, have also been observed within minutes after the administration of Bridion. Tachycardia and bradycardia have been associated with cases of anaphylaxis. “Patients should be closely monitored for hemodynamic changes during and after reversal of neuromuscular blockade, and treatment with anticholinergic agents, such as atropine, should be administered if clinically significant bradycardia is observed,” the agency said.
The most common side effects reported in trials were vomiting, hypotension, pain, headache, and nausea. “Doctors should also advise women using hormonal contraceptives that Bridion may temporarily reduce the contraceptive effect so they must use an alternate method of birth control for a period of time,” the agency said.
Rocuronium bromide and vecuronium bromide are used to paralyze the vocal cords for tracheal intubation, as well as to paralyze patients under general anesthesia and prevent spontaneous breathing during ventilation. Sugammadex is a new molecular entity of the gamma-cyclodextrin class, designed to bind rocuronium and vecuronium.
The Food and Drug Administration approved on Dec. 15 Merck’s sugammadex (Bridion) injection to reverse the effects of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide during surgery.
The safety and efficacy of sugammadex were evaluated in three phase III trials involving 456 participants; most recovered within 5 minutes. An FDA review of the drug found that there was less residual neuromuscular blockade with sugammadex compared to neostigmine, and a 4-minute time savings to extubation and operating room discharge.
“Bridion provides a new treatment option that may help patients recover sooner from medications used for intubation or ventilation during surgery. This drug enables medical personnel to reverse the effects of neuromuscular blocking drugs and restore spontaneous breathing after surgery,” Dr. Sharon Hertz, director of the FDA’s Division of Anesthesia, Analgesia, and Addiction Products, said in a statement.
Although approved in other countries, sugammadex has been in the FDA’s review process since 2007, previously rejected and held up by concerns over anaphylaxis and other issues.
Because of that, sugammadex was further evaluated in a randomized, double-blind, parallel-group, repeat-dose trial. Of the 299 participants treated with Bridion, one person had an anaphylactic reaction. “Clinicians should be aware of the possibility of a hypersensitivity reaction or anaphylaxis and should intervene as appropriate,” the agency said in its statement.
Cases of marked bradycardia, some of which have resulted in cardiac arrest, have also been observed within minutes after the administration of Bridion. Tachycardia and bradycardia have been associated with cases of anaphylaxis. “Patients should be closely monitored for hemodynamic changes during and after reversal of neuromuscular blockade, and treatment with anticholinergic agents, such as atropine, should be administered if clinically significant bradycardia is observed,” the agency said.
The most common side effects reported in trials were vomiting, hypotension, pain, headache, and nausea. “Doctors should also advise women using hormonal contraceptives that Bridion may temporarily reduce the contraceptive effect so they must use an alternate method of birth control for a period of time,” the agency said.
Rocuronium bromide and vecuronium bromide are used to paralyze the vocal cords for tracheal intubation, as well as to paralyze patients under general anesthesia and prevent spontaneous breathing during ventilation. Sugammadex is a new molecular entity of the gamma-cyclodextrin class, designed to bind rocuronium and vecuronium.
Listen Now: Patient Satisfaction Changes Related to Hospital Renovation
As patient satisfaction becomes part of the healthcare quality metric, how does hospital facility design intersect with patient experience, patient satisfaction, and care quality? Two experts, one an architect and the other a hospital medicine clinician and researcher, weigh in on the intersection of architecture and healthcare.
As patient satisfaction becomes part of the healthcare quality metric, how does hospital facility design intersect with patient experience, patient satisfaction, and care quality? Two experts, one an architect and the other a hospital medicine clinician and researcher, weigh in on the intersection of architecture and healthcare.
As patient satisfaction becomes part of the healthcare quality metric, how does hospital facility design intersect with patient experience, patient satisfaction, and care quality? Two experts, one an architect and the other a hospital medicine clinician and researcher, weigh in on the intersection of architecture and healthcare.
SAA patients benefit from upfront eltrombopag combo
Photo courtesy of ASH
ORLANDO, FL—Investigators are pursuing an upfront approval for eltrombopag in combination with immunosuppressive therapy for the treatment of severe aplastic anemia (SAA).
Based on eltrombopag’s single-agent activity in refractory SAA, they hypothesized that its addition to standard immunosuppressive therapy of horse antithymocyte globulin (hATG) and cyclosporine (CsA) in the first-line setting could improve patient outcome.
And, in a phase 2 trial, it did.
“The addition of eltrombopag resulted in over 20% higher overall response rates and complete response rates for both 3 and 6 months,” said Danielle
Townsley, MD, who presented the data at the 2015 ASH Annual Meeting.
Dr Townsley, of the National Heart, Lung, and Blood Institute, National Institutes of Health, in Bethesda, Maryland, presented the findings as abstract LBA-2.*
The US Food and Drug Administration approved eltrombopag to treat refractory SAA in November 2014, and the European Commission approved it in 2015.
Investigators believed eltrombopag in the upfront, treatment-naïve setting could yield higher overall response rates (ORRs) than the 60% to 70% achieved with standard immunosuppressives worldwide.
“[It was] logical to consider treating patients early at the start of their disease,” Dr Townsley said.
So she and her colleagues conducted an investigator-initiated, phase 2, single-center trial of eltrombopag combined with immunosuppressive agents for first-line treatment of SAA.
Study design and patient population
Patients had to have confirmed treatment-naïve SAA, be a minimum of 2 years old, and weigh more than 12 kg. They were excluded if they had prior immunosuppressive therapy with ATG, alemtuzumab, or cyclophosphamide. They were also excluded if they had liver cirrhosis, AST/ALT more than 5 times normal, or Fanconi anemia.
Primary endpoints of the study were complete response (CR) at 6 months and toxicity. Secondary endpoints included ORR and partial response (PR) rate, survival, clonal evolution, and relapse.
Investigators defined CR as having an absolute neutrophil count (ANC) of 1000/μL or higher, a hemoglobin level of 10 g/dL or higher, and a platelet count of 100,000/μL or higher. They defined PR as blood counts no longer meeting criteria for SAA or CR.
All 92 patients received standard hATG (on days 1 to 4) and CsA (for 6 months). Patients in cohort 1 (n=30) also received eltrombopag at 150 mg daily, starting on day 14 for 6 months.
Patients in cohort 2 (n=31) received eltrombopag at 150 mg daily, starting on day 14 for 3 months. And the 31 patients in cohort 3 started 150 mg of daily eltrombopag simultaneously with the immunosuppressants and continued to receive the drug for 6 months.
Investigators assessed response at 3 and 6 months and planned to follow patients for at least 5 years.
Patients in all cohorts were a median of 32 years (range, 3–82), with 21% being younger than 18. About half were male, 66% had less than 1% of a paroxysmal nocturnal hemoglobinuria clone, 37% had a median neutrophil count less than 200/μL, a median reticulocyte count of 20,000/μL (range, 1600–60,400/μL), and a median platelet count of 9000/μL (range, 0–37,000/μL).
Results
At 3 months, the ORR for the entire population was 81%, and the CR rate was 28%. The ORR was 77% in cohorts 1 and 2 and 92% in cohort 3. The CR rate was 17%, 26%, and 44% in cohorts 1, 2, and 3, respectively.
At 6 months, the ORR for the entire population was 86%, and the CR rate was 37%. The ORR was 80%, 87%, and 95% in cohorts 1, 2, and 3, respectively. And the CR rate was 33%, 26%, and 60%, respectively.
Compared to historic rates for patients on hATG and CsA alone, “the addition of eltrombopag resulted in over 20% higher overall response rates and complete response rates for both 3 and 6 months,” Dr Townsley said.
“And for cohort 3, when eltrombopag is given on day 1, the rate of response in evaluable patients to date appears even higher, with 95% overall response rate at 6 months, of which 60% are complete.”
Dr Townsley also noted that, compared to historical experience, neutrophil recovery was more robust in responding patients treated with eltrombopag. Patients on eltrombopag had a mean ANC of 2253/μL, compared with an ANC of 1716/μL for the historic comparator.
“And likewise, more robust platelet recovery was observed with eltrombopag,” Dr Townsley said, with the eltrombopag-treated patients achieving a mean count of 115,262/μL, compared to a mean of 84,303/μL for the historic group.
She added that, among all eltrombopag-treated patients, the median time to neutrophil recovery was 29 days for an ANC greater than 200/μL and 47 days for an ANC greater than 500/μL. In cohort 3—in which eltrombopag was initiated on day 1—those endpoints were achieved in a median of 8 days and 38 days, respectively.
Patients became transfusion-independent for red cells in a median of 42 days and for platelets in a median of 32 days.
Eltrombopag-treated patients had a 99% overall survival at a median follow-up of 18 months (range 1 – 42) when censored for stem cell transplant. When not censored for transplant, their overall survival was 97%.
Adverse events
“The addition of eltrombopag to ATG and cyclosporine was, overall, well tolerated,” Dr Townsley said. “Few grade 3 to 4 events were attributed to eltrombopag.”
Severe cutaneous reactions in 2 patients caused eltrombopag to be stopped, and 10% of patients had grade 2–3 transaminase and bilirubin elevations.
Bone marrow biopsies revealed no increased fibrosis.
One patient with thymoma died while on study due to encephalopathy. And 2 deaths occurred after hematopoietic stem cell transplant, one with relapsed acute myeloid leukemia and the other from relapsed aplastic anemia.
Clonal evolution occurred in 7 patients, 2 who had achieved CR and evolved in 3 and 30 months. Neither patient had bone marrow dysplasia. One patient’s cytogenetics normalized, and the other had stable disease.
“In our protocol, we define any new cytogenetic abnormality as clonal evolution—we have always done this,” Dr Townsley said.
Of the other 5 patients who evolved, 1 achieved a CR and relapsed, 1 achieved a PR and relapsed, 2 achieved a PR, and 1 had no response. Three of these patients had stem cell transplants, 1 had stable disease, and 1 died of acute myeloid leukemia after stem cell transplant.
The investigators concluded that eltrombopag increases complete and overall hematologic response rates in treatment-naïve SAA patients. Immediate introduction of eltrombopag with immunosuppressant therapy may be optimal, and CR does not appear to prevent clonal evolution.
Investigators are currently in the process of conducting a long-term, serial genomic analysis. The study is open for accrual to an extension cohort.
Eltrombopag is marketed as Promacta in the US and Revolade in most countries outside the US.
Dr Townsley disclosed drug and research funding from GlaxoSmithKline and Novartis, developers of eltrombopag. 
*Data in the abstract differ from the presentation.
Photo courtesy of ASH
ORLANDO, FL—Investigators are pursuing an upfront approval for eltrombopag in combination with immunosuppressive therapy for the treatment of severe aplastic anemia (SAA).
Based on eltrombopag’s single-agent activity in refractory SAA, they hypothesized that its addition to standard immunosuppressive therapy of horse antithymocyte globulin (hATG) and cyclosporine (CsA) in the first-line setting could improve patient outcome.
And, in a phase 2 trial, it did.
“The addition of eltrombopag resulted in over 20% higher overall response rates and complete response rates for both 3 and 6 months,” said Danielle
Townsley, MD, who presented the data at the 2015 ASH Annual Meeting.
Dr Townsley, of the National Heart, Lung, and Blood Institute, National Institutes of Health, in Bethesda, Maryland, presented the findings as abstract LBA-2.*
The US Food and Drug Administration approved eltrombopag to treat refractory SAA in November 2014, and the European Commission approved it in 2015.
Investigators believed eltrombopag in the upfront, treatment-naïve setting could yield higher overall response rates (ORRs) than the 60% to 70% achieved with standard immunosuppressives worldwide.
“[It was] logical to consider treating patients early at the start of their disease,” Dr Townsley said.
So she and her colleagues conducted an investigator-initiated, phase 2, single-center trial of eltrombopag combined with immunosuppressive agents for first-line treatment of SAA.
Study design and patient population
Patients had to have confirmed treatment-naïve SAA, be a minimum of 2 years old, and weigh more than 12 kg. They were excluded if they had prior immunosuppressive therapy with ATG, alemtuzumab, or cyclophosphamide. They were also excluded if they had liver cirrhosis, AST/ALT more than 5 times normal, or Fanconi anemia.
Primary endpoints of the study were complete response (CR) at 6 months and toxicity. Secondary endpoints included ORR and partial response (PR) rate, survival, clonal evolution, and relapse.
Investigators defined CR as having an absolute neutrophil count (ANC) of 1000/μL or higher, a hemoglobin level of 10 g/dL or higher, and a platelet count of 100,000/μL or higher. They defined PR as blood counts no longer meeting criteria for SAA or CR.
All 92 patients received standard hATG (on days 1 to 4) and CsA (for 6 months). Patients in cohort 1 (n=30) also received eltrombopag at 150 mg daily, starting on day 14 for 6 months.
Patients in cohort 2 (n=31) received eltrombopag at 150 mg daily, starting on day 14 for 3 months. And the 31 patients in cohort 3 started 150 mg of daily eltrombopag simultaneously with the immunosuppressants and continued to receive the drug for 6 months.
Investigators assessed response at 3 and 6 months and planned to follow patients for at least 5 years.
Patients in all cohorts were a median of 32 years (range, 3–82), with 21% being younger than 18. About half were male, 66% had less than 1% of a paroxysmal nocturnal hemoglobinuria clone, 37% had a median neutrophil count less than 200/μL, a median reticulocyte count of 20,000/μL (range, 1600–60,400/μL), and a median platelet count of 9000/μL (range, 0–37,000/μL).
Results
At 3 months, the ORR for the entire population was 81%, and the CR rate was 28%. The ORR was 77% in cohorts 1 and 2 and 92% in cohort 3. The CR rate was 17%, 26%, and 44% in cohorts 1, 2, and 3, respectively.
At 6 months, the ORR for the entire population was 86%, and the CR rate was 37%. The ORR was 80%, 87%, and 95% in cohorts 1, 2, and 3, respectively. And the CR rate was 33%, 26%, and 60%, respectively.
Compared to historic rates for patients on hATG and CsA alone, “the addition of eltrombopag resulted in over 20% higher overall response rates and complete response rates for both 3 and 6 months,” Dr Townsley said.
“And for cohort 3, when eltrombopag is given on day 1, the rate of response in evaluable patients to date appears even higher, with 95% overall response rate at 6 months, of which 60% are complete.”
Dr Townsley also noted that, compared to historical experience, neutrophil recovery was more robust in responding patients treated with eltrombopag. Patients on eltrombopag had a mean ANC of 2253/μL, compared with an ANC of 1716/μL for the historic comparator.
“And likewise, more robust platelet recovery was observed with eltrombopag,” Dr Townsley said, with the eltrombopag-treated patients achieving a mean count of 115,262/μL, compared to a mean of 84,303/μL for the historic group.
She added that, among all eltrombopag-treated patients, the median time to neutrophil recovery was 29 days for an ANC greater than 200/μL and 47 days for an ANC greater than 500/μL. In cohort 3—in which eltrombopag was initiated on day 1—those endpoints were achieved in a median of 8 days and 38 days, respectively.
Patients became transfusion-independent for red cells in a median of 42 days and for platelets in a median of 32 days.
Eltrombopag-treated patients had a 99% overall survival at a median follow-up of 18 months (range 1 – 42) when censored for stem cell transplant. When not censored for transplant, their overall survival was 97%.
Adverse events
“The addition of eltrombopag to ATG and cyclosporine was, overall, well tolerated,” Dr Townsley said. “Few grade 3 to 4 events were attributed to eltrombopag.”
Severe cutaneous reactions in 2 patients caused eltrombopag to be stopped, and 10% of patients had grade 2–3 transaminase and bilirubin elevations.
Bone marrow biopsies revealed no increased fibrosis.
One patient with thymoma died while on study due to encephalopathy. And 2 deaths occurred after hematopoietic stem cell transplant, one with relapsed acute myeloid leukemia and the other from relapsed aplastic anemia.
Clonal evolution occurred in 7 patients, 2 who had achieved CR and evolved in 3 and 30 months. Neither patient had bone marrow dysplasia. One patient’s cytogenetics normalized, and the other had stable disease.
“In our protocol, we define any new cytogenetic abnormality as clonal evolution—we have always done this,” Dr Townsley said.
Of the other 5 patients who evolved, 1 achieved a CR and relapsed, 1 achieved a PR and relapsed, 2 achieved a PR, and 1 had no response. Three of these patients had stem cell transplants, 1 had stable disease, and 1 died of acute myeloid leukemia after stem cell transplant.
The investigators concluded that eltrombopag increases complete and overall hematologic response rates in treatment-naïve SAA patients. Immediate introduction of eltrombopag with immunosuppressant therapy may be optimal, and CR does not appear to prevent clonal evolution.
Investigators are currently in the process of conducting a long-term, serial genomic analysis. The study is open for accrual to an extension cohort.
Eltrombopag is marketed as Promacta in the US and Revolade in most countries outside the US.
Dr Townsley disclosed drug and research funding from GlaxoSmithKline and Novartis, developers of eltrombopag.
*Data in the abstract differ from the presentation.
Photo courtesy of ASH
ORLANDO, FL—Investigators are pursuing an upfront approval for eltrombopag in combination with immunosuppressive therapy for the treatment of severe aplastic anemia (SAA).
Based on eltrombopag’s single-agent activity in refractory SAA, they hypothesized that its addition to standard immunosuppressive therapy of horse antithymocyte globulin (hATG) and cyclosporine (CsA) in the first-line setting could improve patient outcome.
And, in a phase 2 trial, it did.
“The addition of eltrombopag resulted in over 20% higher overall response rates and complete response rates for both 3 and 6 months,” said Danielle
Townsley, MD, who presented the data at the 2015 ASH Annual Meeting.
Dr Townsley, of the National Heart, Lung, and Blood Institute, National Institutes of Health, in Bethesda, Maryland, presented the findings as abstract LBA-2.*
The US Food and Drug Administration approved eltrombopag to treat refractory SAA in November 2014, and the European Commission approved it in 2015.
Investigators believed eltrombopag in the upfront, treatment-naïve setting could yield higher overall response rates (ORRs) than the 60% to 70% achieved with standard immunosuppressives worldwide.
“[It was] logical to consider treating patients early at the start of their disease,” Dr Townsley said.
So she and her colleagues conducted an investigator-initiated, phase 2, single-center trial of eltrombopag combined with immunosuppressive agents for first-line treatment of SAA.
Study design and patient population
Patients had to have confirmed treatment-naïve SAA, be a minimum of 2 years old, and weigh more than 12 kg. They were excluded if they had prior immunosuppressive therapy with ATG, alemtuzumab, or cyclophosphamide. They were also excluded if they had liver cirrhosis, AST/ALT more than 5 times normal, or Fanconi anemia.
Primary endpoints of the study were complete response (CR) at 6 months and toxicity. Secondary endpoints included ORR and partial response (PR) rate, survival, clonal evolution, and relapse.
Investigators defined CR as having an absolute neutrophil count (ANC) of 1000/μL or higher, a hemoglobin level of 10 g/dL or higher, and a platelet count of 100,000/μL or higher. They defined PR as blood counts no longer meeting criteria for SAA or CR.
All 92 patients received standard hATG (on days 1 to 4) and CsA (for 6 months). Patients in cohort 1 (n=30) also received eltrombopag at 150 mg daily, starting on day 14 for 6 months.
Patients in cohort 2 (n=31) received eltrombopag at 150 mg daily, starting on day 14 for 3 months. And the 31 patients in cohort 3 started 150 mg of daily eltrombopag simultaneously with the immunosuppressants and continued to receive the drug for 6 months.
Investigators assessed response at 3 and 6 months and planned to follow patients for at least 5 years.
Patients in all cohorts were a median of 32 years (range, 3–82), with 21% being younger than 18. About half were male, 66% had less than 1% of a paroxysmal nocturnal hemoglobinuria clone, 37% had a median neutrophil count less than 200/μL, a median reticulocyte count of 20,000/μL (range, 1600–60,400/μL), and a median platelet count of 9000/μL (range, 0–37,000/μL).
Results
At 3 months, the ORR for the entire population was 81%, and the CR rate was 28%. The ORR was 77% in cohorts 1 and 2 and 92% in cohort 3. The CR rate was 17%, 26%, and 44% in cohorts 1, 2, and 3, respectively.
At 6 months, the ORR for the entire population was 86%, and the CR rate was 37%. The ORR was 80%, 87%, and 95% in cohorts 1, 2, and 3, respectively. And the CR rate was 33%, 26%, and 60%, respectively.
Compared to historic rates for patients on hATG and CsA alone, “the addition of eltrombopag resulted in over 20% higher overall response rates and complete response rates for both 3 and 6 months,” Dr Townsley said.
“And for cohort 3, when eltrombopag is given on day 1, the rate of response in evaluable patients to date appears even higher, with 95% overall response rate at 6 months, of which 60% are complete.”
Dr Townsley also noted that, compared to historical experience, neutrophil recovery was more robust in responding patients treated with eltrombopag. Patients on eltrombopag had a mean ANC of 2253/μL, compared with an ANC of 1716/μL for the historic comparator.
“And likewise, more robust platelet recovery was observed with eltrombopag,” Dr Townsley said, with the eltrombopag-treated patients achieving a mean count of 115,262/μL, compared to a mean of 84,303/μL for the historic group.
She added that, among all eltrombopag-treated patients, the median time to neutrophil recovery was 29 days for an ANC greater than 200/μL and 47 days for an ANC greater than 500/μL. In cohort 3—in which eltrombopag was initiated on day 1—those endpoints were achieved in a median of 8 days and 38 days, respectively.
Patients became transfusion-independent for red cells in a median of 42 days and for platelets in a median of 32 days.
Eltrombopag-treated patients had a 99% overall survival at a median follow-up of 18 months (range 1 – 42) when censored for stem cell transplant. When not censored for transplant, their overall survival was 97%.
Adverse events
“The addition of eltrombopag to ATG and cyclosporine was, overall, well tolerated,” Dr Townsley said. “Few grade 3 to 4 events were attributed to eltrombopag.”
Severe cutaneous reactions in 2 patients caused eltrombopag to be stopped, and 10% of patients had grade 2–3 transaminase and bilirubin elevations.
Bone marrow biopsies revealed no increased fibrosis.
One patient with thymoma died while on study due to encephalopathy. And 2 deaths occurred after hematopoietic stem cell transplant, one with relapsed acute myeloid leukemia and the other from relapsed aplastic anemia.
Clonal evolution occurred in 7 patients, 2 who had achieved CR and evolved in 3 and 30 months. Neither patient had bone marrow dysplasia. One patient’s cytogenetics normalized, and the other had stable disease.
“In our protocol, we define any new cytogenetic abnormality as clonal evolution—we have always done this,” Dr Townsley said.
Of the other 5 patients who evolved, 1 achieved a CR and relapsed, 1 achieved a PR and relapsed, 2 achieved a PR, and 1 had no response. Three of these patients had stem cell transplants, 1 had stable disease, and 1 died of acute myeloid leukemia after stem cell transplant.
The investigators concluded that eltrombopag increases complete and overall hematologic response rates in treatment-naïve SAA patients. Immediate introduction of eltrombopag with immunosuppressant therapy may be optimal, and CR does not appear to prevent clonal evolution.
Investigators are currently in the process of conducting a long-term, serial genomic analysis. The study is open for accrual to an extension cohort.
Eltrombopag is marketed as Promacta in the US and Revolade in most countries outside the US.
Dr Townsley disclosed drug and research funding from GlaxoSmithKline and Novartis, developers of eltrombopag.
*Data in the abstract differ from the presentation.
Five-year data suggest ruxolitinib improves survival in MF
ASH Annual Meeting
Photo courtesy of ASH
ORLANDO, FL—Five-year results from the COMFORT-II trial appear to confirm that treatment with ruxolitinib can improve spleen size and survival in patients with myelofibrosis (MF).
“These results pave the way to use ruxolitinib earlier in the course of the disease,” said lead study author Claire Harrison, MD, a consultant hematologist at Guy’s and St. Thomas’ NHS Foundation Trust in London, UK.
Dr Harrison presented the results at the 2015 ASH Annual Meeting (abstract 59).
Ruxolitinib, a JAK1/JAK2 inhibitor, has demonstrated rapid, durable improvements in splenomegaly and MF symptoms, as well as improved survival in the phase 3 COMFORT-I and COMFORT-II studies.
In COMFORT-II, significantly more patients achieved the primary endpoint—a 35% or greater decrease in spleen volume from baseline at week 48—with ruxolitinib than with best available therapy (BAT).
The 3-year follow-up confirmed that spleen volume reductions were sustained, and ruxolitinib treatment remained tolerable with long-term use.
The randomized, open-label, multicenter study included 219 patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.
Two-thirds of patients received ruxolitinib twice daily, and one-third of patients received BAT, which was administered at doses and schedules determined by the investigator.
Almost two-thirds of the patients on the BAT arm crossed over to receive ruxolitinib upon protocol-defined progression following the primary analysis after week 48. All patients randomized to BAT have crossed over or discontinued, Dr Harrison said.
She presented the 5-year final study results, which showed that more than half of the patients (53.4%) experienced significant reductions in spleen size with ruxolitinib therapy and sustained this benefit over a median duration of 3.2 years.
“There was a 33% improvement in overall survival with ruxolitinib as compared to BAT,” she said.
Using a statistical model of survival if patients had not crossed-over to ruxolitinib, the survival benefit was 56% in favor of ruxolitinib.
“The plateau in spleen responses correlates well with the survival advantage,” Dr Harrison said.
She noted that the JAK allele burden was also reduced in the majority of patients who crossed over during the study. A recent bone marrow analysis shows a 20% improvement in fibrosis as well.
Nearly one-quarter of patients from both the ruxolitinib arm and those who crossed over from the BAT arm remained on treatment with ruxolitinib for 5 years.
All adverse events were consistent with previous analyses of treatment with ruxolitinib in MF, Dr Harrison said. The most common adverse events in ruxolitinib-treated patients were thrombocytopenia (52.4%), anemia (49.2%), diarrhea (35.6%), and peripheral edema (33%).
The most common grade 3/4 adverse events included anemia (22.5%), thrombocytopenia (15.2%), pneumonia (5.8%), general physical health deterioration (4.2%), and shortness of breath (4.2%).
“This long-term analysis after a vast number of patient-years shows the ongoing benefit, with no new safety signals and a strong survival message,” Dr Harrison said.
“Hematologists can be confident treating patients with ruxolitinib. It is safe, effective, and leads to significant long-term benefit. Myelofibrosis patients feel better, their spleens are smaller, and they may survive longer.”
COMFORT-II was sponsored by Novartis, which licensed ruxolitinib from Incyte Corporation for development and commercialization outside the US. COMFORT-I was sponsored by Incyte.
ASH Annual Meeting
Photo courtesy of ASH
ORLANDO, FL—Five-year results from the COMFORT-II trial appear to confirm that treatment with ruxolitinib can improve spleen size and survival in patients with myelofibrosis (MF).
“These results pave the way to use ruxolitinib earlier in the course of the disease,” said lead study author Claire Harrison, MD, a consultant hematologist at Guy’s and St. Thomas’ NHS Foundation Trust in London, UK.
Dr Harrison presented the results at the 2015 ASH Annual Meeting (abstract 59).
Ruxolitinib, a JAK1/JAK2 inhibitor, has demonstrated rapid, durable improvements in splenomegaly and MF symptoms, as well as improved survival in the phase 3 COMFORT-I and COMFORT-II studies.
In COMFORT-II, significantly more patients achieved the primary endpoint—a 35% or greater decrease in spleen volume from baseline at week 48—with ruxolitinib than with best available therapy (BAT).
The 3-year follow-up confirmed that spleen volume reductions were sustained, and ruxolitinib treatment remained tolerable with long-term use.
The randomized, open-label, multicenter study included 219 patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.
Two-thirds of patients received ruxolitinib twice daily, and one-third of patients received BAT, which was administered at doses and schedules determined by the investigator.
Almost two-thirds of the patients on the BAT arm crossed over to receive ruxolitinib upon protocol-defined progression following the primary analysis after week 48. All patients randomized to BAT have crossed over or discontinued, Dr Harrison said.
She presented the 5-year final study results, which showed that more than half of the patients (53.4%) experienced significant reductions in spleen size with ruxolitinib therapy and sustained this benefit over a median duration of 3.2 years.
“There was a 33% improvement in overall survival with ruxolitinib as compared to BAT,” she said.
Using a statistical model of survival if patients had not crossed-over to ruxolitinib, the survival benefit was 56% in favor of ruxolitinib.
“The plateau in spleen responses correlates well with the survival advantage,” Dr Harrison said.
She noted that the JAK allele burden was also reduced in the majority of patients who crossed over during the study. A recent bone marrow analysis shows a 20% improvement in fibrosis as well.
Nearly one-quarter of patients from both the ruxolitinib arm and those who crossed over from the BAT arm remained on treatment with ruxolitinib for 5 years.
All adverse events were consistent with previous analyses of treatment with ruxolitinib in MF, Dr Harrison said. The most common adverse events in ruxolitinib-treated patients were thrombocytopenia (52.4%), anemia (49.2%), diarrhea (35.6%), and peripheral edema (33%).
The most common grade 3/4 adverse events included anemia (22.5%), thrombocytopenia (15.2%), pneumonia (5.8%), general physical health deterioration (4.2%), and shortness of breath (4.2%).
“This long-term analysis after a vast number of patient-years shows the ongoing benefit, with no new safety signals and a strong survival message,” Dr Harrison said.
“Hematologists can be confident treating patients with ruxolitinib. It is safe, effective, and leads to significant long-term benefit. Myelofibrosis patients feel better, their spleens are smaller, and they may survive longer.”
COMFORT-II was sponsored by Novartis, which licensed ruxolitinib from Incyte Corporation for development and commercialization outside the US. COMFORT-I was sponsored by Incyte.
ASH Annual Meeting
Photo courtesy of ASH
ORLANDO, FL—Five-year results from the COMFORT-II trial appear to confirm that treatment with ruxolitinib can improve spleen size and survival in patients with myelofibrosis (MF).
“These results pave the way to use ruxolitinib earlier in the course of the disease,” said lead study author Claire Harrison, MD, a consultant hematologist at Guy’s and St. Thomas’ NHS Foundation Trust in London, UK.
Dr Harrison presented the results at the 2015 ASH Annual Meeting (abstract 59).
Ruxolitinib, a JAK1/JAK2 inhibitor, has demonstrated rapid, durable improvements in splenomegaly and MF symptoms, as well as improved survival in the phase 3 COMFORT-I and COMFORT-II studies.
In COMFORT-II, significantly more patients achieved the primary endpoint—a 35% or greater decrease in spleen volume from baseline at week 48—with ruxolitinib than with best available therapy (BAT).
The 3-year follow-up confirmed that spleen volume reductions were sustained, and ruxolitinib treatment remained tolerable with long-term use.
The randomized, open-label, multicenter study included 219 patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.
Two-thirds of patients received ruxolitinib twice daily, and one-third of patients received BAT, which was administered at doses and schedules determined by the investigator.
Almost two-thirds of the patients on the BAT arm crossed over to receive ruxolitinib upon protocol-defined progression following the primary analysis after week 48. All patients randomized to BAT have crossed over or discontinued, Dr Harrison said.
She presented the 5-year final study results, which showed that more than half of the patients (53.4%) experienced significant reductions in spleen size with ruxolitinib therapy and sustained this benefit over a median duration of 3.2 years.
“There was a 33% improvement in overall survival with ruxolitinib as compared to BAT,” she said.
Using a statistical model of survival if patients had not crossed-over to ruxolitinib, the survival benefit was 56% in favor of ruxolitinib.
“The plateau in spleen responses correlates well with the survival advantage,” Dr Harrison said.
She noted that the JAK allele burden was also reduced in the majority of patients who crossed over during the study. A recent bone marrow analysis shows a 20% improvement in fibrosis as well.
Nearly one-quarter of patients from both the ruxolitinib arm and those who crossed over from the BAT arm remained on treatment with ruxolitinib for 5 years.
All adverse events were consistent with previous analyses of treatment with ruxolitinib in MF, Dr Harrison said. The most common adverse events in ruxolitinib-treated patients were thrombocytopenia (52.4%), anemia (49.2%), diarrhea (35.6%), and peripheral edema (33%).
The most common grade 3/4 adverse events included anemia (22.5%), thrombocytopenia (15.2%), pneumonia (5.8%), general physical health deterioration (4.2%), and shortness of breath (4.2%).
“This long-term analysis after a vast number of patient-years shows the ongoing benefit, with no new safety signals and a strong survival message,” Dr Harrison said.
“Hematologists can be confident treating patients with ruxolitinib. It is safe, effective, and leads to significant long-term benefit. Myelofibrosis patients feel better, their spleens are smaller, and they may survive longer.”
COMFORT-II was sponsored by Novartis, which licensed ruxolitinib from Incyte Corporation for development and commercialization outside the US. COMFORT-I was sponsored by Incyte.