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Culture change key in adopting an oncology alternative payment model
SAN DIEGO – If you consider participating in an alternative payment model for your practice, expect to devote a lot of time to work flow changes, according to Blase N. Polite, MD.
“The culture change is one of the hardest things people face as they go into alternative payment models,” Dr. Polite, deputy section chief of clinical operations at the University of Chicago Medical Center, said at the annual meeting of the American College of Physicians.
“You want work flow changes designed to enable you to take better care of your patients in a consistent manner,” he noted. “It has to be designed with a busy clinic and a busy clinician in mind. You want to be able to share the work flow burden among different groups in the system, so it’s important to allow individuals to work at the upper end of their training.”
“We are paid $160 per month throughout the 6-month episode, and you can have as many recurring 6-month episodes as needed, assuming the patient continued to receive chemotherapy in IV or oral format,” Dr. Polite said.
“Our management fees are contingent on documented adherence to care processes,” he added. “We are held accountable to cost of care, quality metrics, and care processes. The shared savings are subject to bringing down costs while maintaining quality. If by year three you have not achieved shared savings, you have two choices: either drop out of the model, or agree to two-sided risk.”
CMS also is collecting detailed stage, molecular data, and recurrence/progression data on each patient.
The ability to perform risk adjustment in your patient population is a cornerstone of any alternative payment model, he said. These include variables such as cancer type, age, sex, selected noncancer comorbidities, receipt of radiation, and participation in a clinical trial.
As an example, Dr. Polite discussed the hypothetical case of a 65-year-old man with lymphoma, Medicare Part D coverage, and no Medicaid.
“If that patient has no comorbidities, the target treatment price is $23,657.80,” he said. “If that patient has been coded for three comorbidities, our target price goes up to $32,090.28. So, you see an almost $10,000 difference in our target price based on whether or not you appropriately coded and accounted for comorbidities in your patient.”
In a 6-month period, about one-third of costs in the university’s oncology care model are related to chemotherapy, another one-third are inpatient costs, “and everything else comes out as rounding error on the back end, such as evaluation and management coding, imaging, and radiation therapy,” Dr. Polite said.
CMS periodically sends national data such as the number of inpatient admissions per 100 patients and ED visits per 100 patients, so the center can compare itself with other practices in the model.
“You have to have a way to think through those data,” he said. “We can look at our drug expenditures and see where it is we’re spending the most money. Are there places where we can save money? Another key area: How do you identify your high-risk patients?”
Currently, Dr. Polite and his associates conduct risk assessments with every new patient, including the Vulnerable Elders Survey (VES-13), the Mini-Cog, the Patient Health Questionnaire–4 (PHQ-4), as well as questions intended to gauge the patient’s social support, financial situation, and health literacy.
“This is triggering within the medical record a best practices alert that is telling the physician there is a recommendation that this patient ought to be referred to social work or geriatric oncology, or psycho-oncology or physical therapy depending on their needs,” he said. “What remains a difficulty is we have about 18% of our patients who have a positive screen. But only in 23% of the cases so far do we have physicians who are actually acting on that screen.”
Clinicians considering adoption of an oncology care model should expect to devote time and resources to additional cancer registry abstraction and data entry, and make electronic medical record changes for data capture and identifying high-risk patients.
“You also want to invest in care coordination and navigation, staffing for after-hours urgent care to avoid emergency department costs, hospitalizations, and readmissions, staffing for pharmacists to manage high-risk patients on complex medications, staffing of additional palliative care providers, and system tools to make sure referral loops are closed,” Dr. Polite said.
“Those are places where money can help you,” he added. “But at the end of the day, money cannot help getting all the staff to collect and act upon the information provided to them.”
Dr. Polite disclosed that he has received research grants from Merck and is a consultant for GLG and Pfizer.
SAN DIEGO – If you consider participating in an alternative payment model for your practice, expect to devote a lot of time to work flow changes, according to Blase N. Polite, MD.
“The culture change is one of the hardest things people face as they go into alternative payment models,” Dr. Polite, deputy section chief of clinical operations at the University of Chicago Medical Center, said at the annual meeting of the American College of Physicians.
“You want work flow changes designed to enable you to take better care of your patients in a consistent manner,” he noted. “It has to be designed with a busy clinic and a busy clinician in mind. You want to be able to share the work flow burden among different groups in the system, so it’s important to allow individuals to work at the upper end of their training.”
“We are paid $160 per month throughout the 6-month episode, and you can have as many recurring 6-month episodes as needed, assuming the patient continued to receive chemotherapy in IV or oral format,” Dr. Polite said.
“Our management fees are contingent on documented adherence to care processes,” he added. “We are held accountable to cost of care, quality metrics, and care processes. The shared savings are subject to bringing down costs while maintaining quality. If by year three you have not achieved shared savings, you have two choices: either drop out of the model, or agree to two-sided risk.”
CMS also is collecting detailed stage, molecular data, and recurrence/progression data on each patient.
The ability to perform risk adjustment in your patient population is a cornerstone of any alternative payment model, he said. These include variables such as cancer type, age, sex, selected noncancer comorbidities, receipt of radiation, and participation in a clinical trial.
As an example, Dr. Polite discussed the hypothetical case of a 65-year-old man with lymphoma, Medicare Part D coverage, and no Medicaid.
“If that patient has no comorbidities, the target treatment price is $23,657.80,” he said. “If that patient has been coded for three comorbidities, our target price goes up to $32,090.28. So, you see an almost $10,000 difference in our target price based on whether or not you appropriately coded and accounted for comorbidities in your patient.”
In a 6-month period, about one-third of costs in the university’s oncology care model are related to chemotherapy, another one-third are inpatient costs, “and everything else comes out as rounding error on the back end, such as evaluation and management coding, imaging, and radiation therapy,” Dr. Polite said.
CMS periodically sends national data such as the number of inpatient admissions per 100 patients and ED visits per 100 patients, so the center can compare itself with other practices in the model.
“You have to have a way to think through those data,” he said. “We can look at our drug expenditures and see where it is we’re spending the most money. Are there places where we can save money? Another key area: How do you identify your high-risk patients?”
Currently, Dr. Polite and his associates conduct risk assessments with every new patient, including the Vulnerable Elders Survey (VES-13), the Mini-Cog, the Patient Health Questionnaire–4 (PHQ-4), as well as questions intended to gauge the patient’s social support, financial situation, and health literacy.
“This is triggering within the medical record a best practices alert that is telling the physician there is a recommendation that this patient ought to be referred to social work or geriatric oncology, or psycho-oncology or physical therapy depending on their needs,” he said. “What remains a difficulty is we have about 18% of our patients who have a positive screen. But only in 23% of the cases so far do we have physicians who are actually acting on that screen.”
Clinicians considering adoption of an oncology care model should expect to devote time and resources to additional cancer registry abstraction and data entry, and make electronic medical record changes for data capture and identifying high-risk patients.
“You also want to invest in care coordination and navigation, staffing for after-hours urgent care to avoid emergency department costs, hospitalizations, and readmissions, staffing for pharmacists to manage high-risk patients on complex medications, staffing of additional palliative care providers, and system tools to make sure referral loops are closed,” Dr. Polite said.
“Those are places where money can help you,” he added. “But at the end of the day, money cannot help getting all the staff to collect and act upon the information provided to them.”
Dr. Polite disclosed that he has received research grants from Merck and is a consultant for GLG and Pfizer.
SAN DIEGO – If you consider participating in an alternative payment model for your practice, expect to devote a lot of time to work flow changes, according to Blase N. Polite, MD.
“The culture change is one of the hardest things people face as they go into alternative payment models,” Dr. Polite, deputy section chief of clinical operations at the University of Chicago Medical Center, said at the annual meeting of the American College of Physicians.
“You want work flow changes designed to enable you to take better care of your patients in a consistent manner,” he noted. “It has to be designed with a busy clinic and a busy clinician in mind. You want to be able to share the work flow burden among different groups in the system, so it’s important to allow individuals to work at the upper end of their training.”
“We are paid $160 per month throughout the 6-month episode, and you can have as many recurring 6-month episodes as needed, assuming the patient continued to receive chemotherapy in IV or oral format,” Dr. Polite said.
“Our management fees are contingent on documented adherence to care processes,” he added. “We are held accountable to cost of care, quality metrics, and care processes. The shared savings are subject to bringing down costs while maintaining quality. If by year three you have not achieved shared savings, you have two choices: either drop out of the model, or agree to two-sided risk.”
CMS also is collecting detailed stage, molecular data, and recurrence/progression data on each patient.
The ability to perform risk adjustment in your patient population is a cornerstone of any alternative payment model, he said. These include variables such as cancer type, age, sex, selected noncancer comorbidities, receipt of radiation, and participation in a clinical trial.
As an example, Dr. Polite discussed the hypothetical case of a 65-year-old man with lymphoma, Medicare Part D coverage, and no Medicaid.
“If that patient has no comorbidities, the target treatment price is $23,657.80,” he said. “If that patient has been coded for three comorbidities, our target price goes up to $32,090.28. So, you see an almost $10,000 difference in our target price based on whether or not you appropriately coded and accounted for comorbidities in your patient.”
In a 6-month period, about one-third of costs in the university’s oncology care model are related to chemotherapy, another one-third are inpatient costs, “and everything else comes out as rounding error on the back end, such as evaluation and management coding, imaging, and radiation therapy,” Dr. Polite said.
CMS periodically sends national data such as the number of inpatient admissions per 100 patients and ED visits per 100 patients, so the center can compare itself with other practices in the model.
“You have to have a way to think through those data,” he said. “We can look at our drug expenditures and see where it is we’re spending the most money. Are there places where we can save money? Another key area: How do you identify your high-risk patients?”
Currently, Dr. Polite and his associates conduct risk assessments with every new patient, including the Vulnerable Elders Survey (VES-13), the Mini-Cog, the Patient Health Questionnaire–4 (PHQ-4), as well as questions intended to gauge the patient’s social support, financial situation, and health literacy.
“This is triggering within the medical record a best practices alert that is telling the physician there is a recommendation that this patient ought to be referred to social work or geriatric oncology, or psycho-oncology or physical therapy depending on their needs,” he said. “What remains a difficulty is we have about 18% of our patients who have a positive screen. But only in 23% of the cases so far do we have physicians who are actually acting on that screen.”
Clinicians considering adoption of an oncology care model should expect to devote time and resources to additional cancer registry abstraction and data entry, and make electronic medical record changes for data capture and identifying high-risk patients.
“You also want to invest in care coordination and navigation, staffing for after-hours urgent care to avoid emergency department costs, hospitalizations, and readmissions, staffing for pharmacists to manage high-risk patients on complex medications, staffing of additional palliative care providers, and system tools to make sure referral loops are closed,” Dr. Polite said.
“Those are places where money can help you,” he added. “But at the end of the day, money cannot help getting all the staff to collect and act upon the information provided to them.”
Dr. Polite disclosed that he has received research grants from Merck and is a consultant for GLG and Pfizer.
EXPERT ANALYSIS AT ACP INTERNAL MEDICINE
Severe Refractory Atopic Dermatitis With Elevated Serum IgE Treated With Omalizumab
To the Editor:
Atopic dermatitis (AD) is a common skin condition with an increasing prevalence, affecting up to 20% of children and 3% of adults.1,2 More than 80% of patients with AD have elevated IgE levels.3,4 IgE modulates the inflammatory response in AD in several ways including “a biphasic immediate/late phase reaction, allergen presentation by IgE-bearing Langerhans cells, allergen-induced activation of IgE-bearing macrophages, and IgE autoreactivity to human proteins.”5 Historically, most therapies have focused on mitigating the allergic symptoms caused by degranulated effector cells, such as antihistamines. However, a new class of biologically engineered medications (eg, anti-IgE [omalizumab]) aim to prevent the initiation of the allergic response.6 Variable success has been reported using omalizumab in the treatment of AD, though the majority of studies have shown improvement, especially when used in combination with conventional therapies.4,5,7-22 Omalizumab dosage is determined by body weight and pretreatment serum total IgE levels and is administered via subcutaneous injections every 2 to 4 weeks.6,7,23-26 However, the dosing tables are based on asthma therapy, in which serum IgE levels may be much lower than chronic AD,7,24 and the appropriate dosage in AD patients with markedly elevated IgE is unclear. We report an interesting case of a 57-year-old man with erythroderma from long-standing severe chronic AD that was unresponsive to conventional therapy as well as an associated serum IgE level of 17,183 IU/mL who dramatically improved when omalizumab was added to his treatment regimen.
A 57-year-old man presented with essentially 100% body surface area involvement of AD with erythroderma and pruritus. Severe AD developed at infancy and cleared at 5 years of age; childhood onset of asthma was responsive to theophylline and oral inhalers. He developed recurrent AD and asthma at 38 years of age, which was progressive and developed into severe recalcitrant erythroderma by 50 years of age. His AD was unresponsive to multiple therapies, including topical steroids, antibiotics, tacrolimus, bleach baths, antihistamines, methotrexate (15 mg weekly for 1 year, then 12.5 mg weekly for 6 months), UVB phototherapy, and psoralen plus UVA photochemotherapy. He had minimal improvement with cyclosporine (200 mg daily for 4 weeks) and mycophenolate mofetil (3 g daily), and required systemic steroids for relief. The skin was violaceous and lichenified (Figure, A). Laboratory studies were normal, except for a serum IgE level of 17,183 IU/mL (reference range, <150 IU/mL) and peripheral blood eosinophilia up to 29.8% (reference range, 1%–5%) of the differential. Skin biopsies showed AD progressing to lichen simplex chronicus. Omalizumab was added to the therapeutic regimen at a dose of 375 mg every 2 weeks, with noticeable improvement after 3 months. The patient had approximately 80% to 90% clearing with resolution of erythroderma and pruritus, and only limited residual lichenification (Figure, B). The mycophenolate was tapered slowly, and the patient experienced a mild flare at 1 g daily. He is presently on 1 g of mycophenolate daily and omalizumab (375 mg every 2 weeks) and remains remarkably improved. His IgE level decreased to 11,983 IU/mL.
Omalizumab is a monoclonal IgG1 antibody that specifically binds to the FcεRI domain of serum IgE. It blocks binding to high-affinity receptors on effector cells, primarily mast cells, basophils, macrophages, and dendritic cells; it also decreases free IgE serum levels and downregulates the IgE receptor.4,6-10,23-25,27,28 Currently, omalizumab is US Food and Drug Administration approved for moderate to severe persistent asthma in patients 6 years or older with a positive aeroallergen skin test and IgE levels up to 700 IU/mL.6,7,23-25,27,28
However, scattered case reports and small case series have described variable success in the treatment of severe AD that is unresponsive to conventional therapy in patients with markedly elevated serum IgE levels.4,5,7-22 The majority of patients (approximately 80% of published cases yielded by a PubMed search of articles indexed for MEDLINE using the search terms omalizumab and atopic dermatitis) showed improvement when measured by clinical severity scores and quality of life improvement, especially when used in conjunction with conventional therapy. Possible reasons for reported treatment failure include insufficient dosage, lack of established treatment guidelines for markedly elevated serum IgE levels, severity of disease, or variable response with failure to lower IgE level below a required threshold.7,9,23,24,27
Krathen and Hsu9 reported treatment failure with omalizumab for AD in 3 patients with serum IgE levels ranging from 5440 and 24,400 IU/mL, and one review indicated omalizumab may work best in patients with only moderately elevated serum IgE levels.21 However, Toledo et al18 reported efficacy of low-dose omalizumab for pretreatment IgE levels up to 30,000 IU/mL in 6 of 11 reported cases. The pretreatment serum IgE level is not predictive of response, and lowering the serum IgE level without normalization can be efficacious,12,23 as in the current case. Serum IgE levels are not used for monitoring therapeutic response or calculating future dosing, given potential increases in serum IgE levels during and after therapy (for up to 12 months) secondary to the formation of anti-IgE:IgE complexes.6,28 Omalizumab appears most effective when used in combination with conventional therapies. Hopefully ongoing studies will further elucidate the role of omalizumab in recalcitrant AD with elevated serum IgE levels.
- Schultz-Larsen F, Diepgen T, Svennson A. The occurrence of atopic dermatitis in north Europe: an international questionnaire study. J Am Acad Dermatol. 1996;34:760-764.
- Laughter D, Istvan JA, Tofte SJ, et al. The presence of atopic dermatitis in Oregon schoolchildren. J Am Acad Dermatol. 2000;43:649-655.
- Jones HE, Inouye JC, McGerity JL, et al. Atopic disease and serum immunoglobulin-E. Br J Dermatol. 1975;92:17-25.
- Abramovits W. A clinician’s paradigm in the treatment of atopic dermatitis. J Am Acad Dermatol. 2005;53(1, suppl 1):570-577.
- Leung D, Soter N. Cellular and immunologic mechanisms in atopic dermatitis. J Am Acad Dermatol. 2001;44(suppl):S1-S12.
- US Food and Drug Administration. Briefing document on safety. Omalizumab (Xolair) (recombinant humanized monoclonal antibody to IgE) for treatment of allergic asthma. http://www.fda.gov/ohrms/dockets/ac/03/briefing/3952B1_02_FDA-Xolair-Safety.pdf. Published April 18, 2003. Accessed June 23, 2014.
- Lane JE, Cheyney JM, Lane TN, et al. Treatment of recalcitrant atopic dermatitis with omalizumab. J Am Acad Dermatol. 2006;54:68-72.
- Caruso C, Gaeta F, Valluzzi RL, et al. Omalizumab efficacy in a girl with atopic eczema. Allergy. 2010;65:278-279.
- Krathen RA, Hsu S. Failure of omalizumab for the treatment of severe atopic dermatitis. J Am Dermatol. 2005;53:338-340.
- Fernández-Antón Martínez MC, Leis-Dosil V, Alfageme-Roldán F, et al. Omalizumab for the treatment of Atopic Dermatitis. Actas Dermosifiliogr. 2012;103:624-628.
- Pelaia G, Gallelli L, Romeo P, et al. Omalizumab decreases exacerbation frequency, oral intake of corticosteroids and peripheral blood eosinophils in atopic patients with uncontrolled asthma. Int J Clin Pharmacol Ther. 2011;49:713-721.
- Belloni B, Ziai M, Lim A, et al. Low-dose anti-IgE therapy in patients with atopic eczema with high serum IgE levels. J Allergy Clin Immunol. 2007;120:1223-1225.
- Park SY, Choi MR, Na JI, et al. Recalcitrant atopic dermatitis treated with omalizumab. Ann Dermatol. 2010;22:349-352.
- Velling P, Skowasch D, Pabst S. Improvement of quality of life in patients with concomitant allergic asthma and atopic dermatitis: one year follow-up of omalizumab therapy. Eur J Med Res. 2011;15:407-410.
- Amrol D. Anti-immunoglobulin E in the treatment of refractory atopic dermatitis. South Med J. 2010;103:554-558.
- Heil PM, Maurer D, Klein B, et al. Omalizumab therapy in atopic dermatitis: depletion of IgE does not improve the clinical course-a randomized, placebo-controlled and double blind study. J Dtsch Dermatol Ges. 2010;8:990-998.
- Ramírez del Pozo ME, Contreras Contreras E, López Tiro J, et al. Omalizumab (anti-IgE antibody) in the treatment of severe atopic dermatitis. J Investig Allergol Clin Immunol. 2011;21:416-417.
- Toledo F, Silvestre JF, Muñoz C. Combined therapy with low-dose omalizumab and intravenous immunoglobulin for severe atopic dermatitis: report of four cases. J Eur Acad Dermatol Venereol. 2012;26:1325-1327.
- Sheinkopf LE, Rafi AW, Katz RM. Efficacy of omalizumab in the treatment of atopic dermatitis: a pilot study. Allergy Asthma Proc. 2008;29:530-537.
- Incorvia C, Pravettoni C, Mauro M, et al. Effectiveness of omalizumab in a patient with severe asthma and atopic dermatitis. Monaldi Arch Chest Dis. 2008:69:78-80.
- Schmitt J, Schäkel K. Omalizumab as a therapeutic option in atopic eczema. Current evidence and potential benefit [in German]. Hautarzt. 2007;58:130-132.
- Thaiwat S, Sangasapaviliya A. Omalizumab treatment in severe atopic dermatitis. Asian Pac J Allergy Immunol. 2011;29:357-360.
- Kopp MV. Omalizumab: anti-IgE therapy in allergy. Curr Allergy Asthma Rep. 2011;11:101-106.
- Vichyanond P. Omalizumab in allergic diseases, a recent review. Asian Pc J Allergy Immunol. 2011;29:209-219.
- Scheinfeld N. Omalizumab. A recombinant humanized monoclonal IgE-blocking antibody. Dermatol Online J. 2005;11:2.
- Lowe PJ, Georgiou P, Canvin J. Revision of omalizumab dosing table for dosing every 4 instead of 2 weeks for specific ranges of bodyweight and baseline IgE [published online ahead of print December 8, 2014]. Regul Toxicol Pharmacol. 2015;71:68-77.
- Vigo PG, Girgis KR, Pfuetze BL, et al. Efficacy of anti-IgE therapy in patients with atopic dermatitis. J Am Acad Dermatol. 2006;55:168-170.
- Hanifin J, Chan S. Biochemical and immunologic mechanisms in atopic dermatitis: new targets for emerging therapies. J Am Acad Dermatol. 1999;41:72-77.
To the Editor:
Atopic dermatitis (AD) is a common skin condition with an increasing prevalence, affecting up to 20% of children and 3% of adults.1,2 More than 80% of patients with AD have elevated IgE levels.3,4 IgE modulates the inflammatory response in AD in several ways including “a biphasic immediate/late phase reaction, allergen presentation by IgE-bearing Langerhans cells, allergen-induced activation of IgE-bearing macrophages, and IgE autoreactivity to human proteins.”5 Historically, most therapies have focused on mitigating the allergic symptoms caused by degranulated effector cells, such as antihistamines. However, a new class of biologically engineered medications (eg, anti-IgE [omalizumab]) aim to prevent the initiation of the allergic response.6 Variable success has been reported using omalizumab in the treatment of AD, though the majority of studies have shown improvement, especially when used in combination with conventional therapies.4,5,7-22 Omalizumab dosage is determined by body weight and pretreatment serum total IgE levels and is administered via subcutaneous injections every 2 to 4 weeks.6,7,23-26 However, the dosing tables are based on asthma therapy, in which serum IgE levels may be much lower than chronic AD,7,24 and the appropriate dosage in AD patients with markedly elevated IgE is unclear. We report an interesting case of a 57-year-old man with erythroderma from long-standing severe chronic AD that was unresponsive to conventional therapy as well as an associated serum IgE level of 17,183 IU/mL who dramatically improved when omalizumab was added to his treatment regimen.
A 57-year-old man presented with essentially 100% body surface area involvement of AD with erythroderma and pruritus. Severe AD developed at infancy and cleared at 5 years of age; childhood onset of asthma was responsive to theophylline and oral inhalers. He developed recurrent AD and asthma at 38 years of age, which was progressive and developed into severe recalcitrant erythroderma by 50 years of age. His AD was unresponsive to multiple therapies, including topical steroids, antibiotics, tacrolimus, bleach baths, antihistamines, methotrexate (15 mg weekly for 1 year, then 12.5 mg weekly for 6 months), UVB phototherapy, and psoralen plus UVA photochemotherapy. He had minimal improvement with cyclosporine (200 mg daily for 4 weeks) and mycophenolate mofetil (3 g daily), and required systemic steroids for relief. The skin was violaceous and lichenified (Figure, A). Laboratory studies were normal, except for a serum IgE level of 17,183 IU/mL (reference range, <150 IU/mL) and peripheral blood eosinophilia up to 29.8% (reference range, 1%–5%) of the differential. Skin biopsies showed AD progressing to lichen simplex chronicus. Omalizumab was added to the therapeutic regimen at a dose of 375 mg every 2 weeks, with noticeable improvement after 3 months. The patient had approximately 80% to 90% clearing with resolution of erythroderma and pruritus, and only limited residual lichenification (Figure, B). The mycophenolate was tapered slowly, and the patient experienced a mild flare at 1 g daily. He is presently on 1 g of mycophenolate daily and omalizumab (375 mg every 2 weeks) and remains remarkably improved. His IgE level decreased to 11,983 IU/mL.
Omalizumab is a monoclonal IgG1 antibody that specifically binds to the FcεRI domain of serum IgE. It blocks binding to high-affinity receptors on effector cells, primarily mast cells, basophils, macrophages, and dendritic cells; it also decreases free IgE serum levels and downregulates the IgE receptor.4,6-10,23-25,27,28 Currently, omalizumab is US Food and Drug Administration approved for moderate to severe persistent asthma in patients 6 years or older with a positive aeroallergen skin test and IgE levels up to 700 IU/mL.6,7,23-25,27,28
However, scattered case reports and small case series have described variable success in the treatment of severe AD that is unresponsive to conventional therapy in patients with markedly elevated serum IgE levels.4,5,7-22 The majority of patients (approximately 80% of published cases yielded by a PubMed search of articles indexed for MEDLINE using the search terms omalizumab and atopic dermatitis) showed improvement when measured by clinical severity scores and quality of life improvement, especially when used in conjunction with conventional therapy. Possible reasons for reported treatment failure include insufficient dosage, lack of established treatment guidelines for markedly elevated serum IgE levels, severity of disease, or variable response with failure to lower IgE level below a required threshold.7,9,23,24,27
Krathen and Hsu9 reported treatment failure with omalizumab for AD in 3 patients with serum IgE levels ranging from 5440 and 24,400 IU/mL, and one review indicated omalizumab may work best in patients with only moderately elevated serum IgE levels.21 However, Toledo et al18 reported efficacy of low-dose omalizumab for pretreatment IgE levels up to 30,000 IU/mL in 6 of 11 reported cases. The pretreatment serum IgE level is not predictive of response, and lowering the serum IgE level without normalization can be efficacious,12,23 as in the current case. Serum IgE levels are not used for monitoring therapeutic response or calculating future dosing, given potential increases in serum IgE levels during and after therapy (for up to 12 months) secondary to the formation of anti-IgE:IgE complexes.6,28 Omalizumab appears most effective when used in combination with conventional therapies. Hopefully ongoing studies will further elucidate the role of omalizumab in recalcitrant AD with elevated serum IgE levels.
To the Editor:
Atopic dermatitis (AD) is a common skin condition with an increasing prevalence, affecting up to 20% of children and 3% of adults.1,2 More than 80% of patients with AD have elevated IgE levels.3,4 IgE modulates the inflammatory response in AD in several ways including “a biphasic immediate/late phase reaction, allergen presentation by IgE-bearing Langerhans cells, allergen-induced activation of IgE-bearing macrophages, and IgE autoreactivity to human proteins.”5 Historically, most therapies have focused on mitigating the allergic symptoms caused by degranulated effector cells, such as antihistamines. However, a new class of biologically engineered medications (eg, anti-IgE [omalizumab]) aim to prevent the initiation of the allergic response.6 Variable success has been reported using omalizumab in the treatment of AD, though the majority of studies have shown improvement, especially when used in combination with conventional therapies.4,5,7-22 Omalizumab dosage is determined by body weight and pretreatment serum total IgE levels and is administered via subcutaneous injections every 2 to 4 weeks.6,7,23-26 However, the dosing tables are based on asthma therapy, in which serum IgE levels may be much lower than chronic AD,7,24 and the appropriate dosage in AD patients with markedly elevated IgE is unclear. We report an interesting case of a 57-year-old man with erythroderma from long-standing severe chronic AD that was unresponsive to conventional therapy as well as an associated serum IgE level of 17,183 IU/mL who dramatically improved when omalizumab was added to his treatment regimen.
A 57-year-old man presented with essentially 100% body surface area involvement of AD with erythroderma and pruritus. Severe AD developed at infancy and cleared at 5 years of age; childhood onset of asthma was responsive to theophylline and oral inhalers. He developed recurrent AD and asthma at 38 years of age, which was progressive and developed into severe recalcitrant erythroderma by 50 years of age. His AD was unresponsive to multiple therapies, including topical steroids, antibiotics, tacrolimus, bleach baths, antihistamines, methotrexate (15 mg weekly for 1 year, then 12.5 mg weekly for 6 months), UVB phototherapy, and psoralen plus UVA photochemotherapy. He had minimal improvement with cyclosporine (200 mg daily for 4 weeks) and mycophenolate mofetil (3 g daily), and required systemic steroids for relief. The skin was violaceous and lichenified (Figure, A). Laboratory studies were normal, except for a serum IgE level of 17,183 IU/mL (reference range, <150 IU/mL) and peripheral blood eosinophilia up to 29.8% (reference range, 1%–5%) of the differential. Skin biopsies showed AD progressing to lichen simplex chronicus. Omalizumab was added to the therapeutic regimen at a dose of 375 mg every 2 weeks, with noticeable improvement after 3 months. The patient had approximately 80% to 90% clearing with resolution of erythroderma and pruritus, and only limited residual lichenification (Figure, B). The mycophenolate was tapered slowly, and the patient experienced a mild flare at 1 g daily. He is presently on 1 g of mycophenolate daily and omalizumab (375 mg every 2 weeks) and remains remarkably improved. His IgE level decreased to 11,983 IU/mL.
Omalizumab is a monoclonal IgG1 antibody that specifically binds to the FcεRI domain of serum IgE. It blocks binding to high-affinity receptors on effector cells, primarily mast cells, basophils, macrophages, and dendritic cells; it also decreases free IgE serum levels and downregulates the IgE receptor.4,6-10,23-25,27,28 Currently, omalizumab is US Food and Drug Administration approved for moderate to severe persistent asthma in patients 6 years or older with a positive aeroallergen skin test and IgE levels up to 700 IU/mL.6,7,23-25,27,28
However, scattered case reports and small case series have described variable success in the treatment of severe AD that is unresponsive to conventional therapy in patients with markedly elevated serum IgE levels.4,5,7-22 The majority of patients (approximately 80% of published cases yielded by a PubMed search of articles indexed for MEDLINE using the search terms omalizumab and atopic dermatitis) showed improvement when measured by clinical severity scores and quality of life improvement, especially when used in conjunction with conventional therapy. Possible reasons for reported treatment failure include insufficient dosage, lack of established treatment guidelines for markedly elevated serum IgE levels, severity of disease, or variable response with failure to lower IgE level below a required threshold.7,9,23,24,27
Krathen and Hsu9 reported treatment failure with omalizumab for AD in 3 patients with serum IgE levels ranging from 5440 and 24,400 IU/mL, and one review indicated omalizumab may work best in patients with only moderately elevated serum IgE levels.21 However, Toledo et al18 reported efficacy of low-dose omalizumab for pretreatment IgE levels up to 30,000 IU/mL in 6 of 11 reported cases. The pretreatment serum IgE level is not predictive of response, and lowering the serum IgE level without normalization can be efficacious,12,23 as in the current case. Serum IgE levels are not used for monitoring therapeutic response or calculating future dosing, given potential increases in serum IgE levels during and after therapy (for up to 12 months) secondary to the formation of anti-IgE:IgE complexes.6,28 Omalizumab appears most effective when used in combination with conventional therapies. Hopefully ongoing studies will further elucidate the role of omalizumab in recalcitrant AD with elevated serum IgE levels.
- Schultz-Larsen F, Diepgen T, Svennson A. The occurrence of atopic dermatitis in north Europe: an international questionnaire study. J Am Acad Dermatol. 1996;34:760-764.
- Laughter D, Istvan JA, Tofte SJ, et al. The presence of atopic dermatitis in Oregon schoolchildren. J Am Acad Dermatol. 2000;43:649-655.
- Jones HE, Inouye JC, McGerity JL, et al. Atopic disease and serum immunoglobulin-E. Br J Dermatol. 1975;92:17-25.
- Abramovits W. A clinician’s paradigm in the treatment of atopic dermatitis. J Am Acad Dermatol. 2005;53(1, suppl 1):570-577.
- Leung D, Soter N. Cellular and immunologic mechanisms in atopic dermatitis. J Am Acad Dermatol. 2001;44(suppl):S1-S12.
- US Food and Drug Administration. Briefing document on safety. Omalizumab (Xolair) (recombinant humanized monoclonal antibody to IgE) for treatment of allergic asthma. http://www.fda.gov/ohrms/dockets/ac/03/briefing/3952B1_02_FDA-Xolair-Safety.pdf. Published April 18, 2003. Accessed June 23, 2014.
- Lane JE, Cheyney JM, Lane TN, et al. Treatment of recalcitrant atopic dermatitis with omalizumab. J Am Acad Dermatol. 2006;54:68-72.
- Caruso C, Gaeta F, Valluzzi RL, et al. Omalizumab efficacy in a girl with atopic eczema. Allergy. 2010;65:278-279.
- Krathen RA, Hsu S. Failure of omalizumab for the treatment of severe atopic dermatitis. J Am Dermatol. 2005;53:338-340.
- Fernández-Antón Martínez MC, Leis-Dosil V, Alfageme-Roldán F, et al. Omalizumab for the treatment of Atopic Dermatitis. Actas Dermosifiliogr. 2012;103:624-628.
- Pelaia G, Gallelli L, Romeo P, et al. Omalizumab decreases exacerbation frequency, oral intake of corticosteroids and peripheral blood eosinophils in atopic patients with uncontrolled asthma. Int J Clin Pharmacol Ther. 2011;49:713-721.
- Belloni B, Ziai M, Lim A, et al. Low-dose anti-IgE therapy in patients with atopic eczema with high serum IgE levels. J Allergy Clin Immunol. 2007;120:1223-1225.
- Park SY, Choi MR, Na JI, et al. Recalcitrant atopic dermatitis treated with omalizumab. Ann Dermatol. 2010;22:349-352.
- Velling P, Skowasch D, Pabst S. Improvement of quality of life in patients with concomitant allergic asthma and atopic dermatitis: one year follow-up of omalizumab therapy. Eur J Med Res. 2011;15:407-410.
- Amrol D. Anti-immunoglobulin E in the treatment of refractory atopic dermatitis. South Med J. 2010;103:554-558.
- Heil PM, Maurer D, Klein B, et al. Omalizumab therapy in atopic dermatitis: depletion of IgE does not improve the clinical course-a randomized, placebo-controlled and double blind study. J Dtsch Dermatol Ges. 2010;8:990-998.
- Ramírez del Pozo ME, Contreras Contreras E, López Tiro J, et al. Omalizumab (anti-IgE antibody) in the treatment of severe atopic dermatitis. J Investig Allergol Clin Immunol. 2011;21:416-417.
- Toledo F, Silvestre JF, Muñoz C. Combined therapy with low-dose omalizumab and intravenous immunoglobulin for severe atopic dermatitis: report of four cases. J Eur Acad Dermatol Venereol. 2012;26:1325-1327.
- Sheinkopf LE, Rafi AW, Katz RM. Efficacy of omalizumab in the treatment of atopic dermatitis: a pilot study. Allergy Asthma Proc. 2008;29:530-537.
- Incorvia C, Pravettoni C, Mauro M, et al. Effectiveness of omalizumab in a patient with severe asthma and atopic dermatitis. Monaldi Arch Chest Dis. 2008:69:78-80.
- Schmitt J, Schäkel K. Omalizumab as a therapeutic option in atopic eczema. Current evidence and potential benefit [in German]. Hautarzt. 2007;58:130-132.
- Thaiwat S, Sangasapaviliya A. Omalizumab treatment in severe atopic dermatitis. Asian Pac J Allergy Immunol. 2011;29:357-360.
- Kopp MV. Omalizumab: anti-IgE therapy in allergy. Curr Allergy Asthma Rep. 2011;11:101-106.
- Vichyanond P. Omalizumab in allergic diseases, a recent review. Asian Pc J Allergy Immunol. 2011;29:209-219.
- Scheinfeld N. Omalizumab. A recombinant humanized monoclonal IgE-blocking antibody. Dermatol Online J. 2005;11:2.
- Lowe PJ, Georgiou P, Canvin J. Revision of omalizumab dosing table for dosing every 4 instead of 2 weeks for specific ranges of bodyweight and baseline IgE [published online ahead of print December 8, 2014]. Regul Toxicol Pharmacol. 2015;71:68-77.
- Vigo PG, Girgis KR, Pfuetze BL, et al. Efficacy of anti-IgE therapy in patients with atopic dermatitis. J Am Acad Dermatol. 2006;55:168-170.
- Hanifin J, Chan S. Biochemical and immunologic mechanisms in atopic dermatitis: new targets for emerging therapies. J Am Acad Dermatol. 1999;41:72-77.
- Schultz-Larsen F, Diepgen T, Svennson A. The occurrence of atopic dermatitis in north Europe: an international questionnaire study. J Am Acad Dermatol. 1996;34:760-764.
- Laughter D, Istvan JA, Tofte SJ, et al. The presence of atopic dermatitis in Oregon schoolchildren. J Am Acad Dermatol. 2000;43:649-655.
- Jones HE, Inouye JC, McGerity JL, et al. Atopic disease and serum immunoglobulin-E. Br J Dermatol. 1975;92:17-25.
- Abramovits W. A clinician’s paradigm in the treatment of atopic dermatitis. J Am Acad Dermatol. 2005;53(1, suppl 1):570-577.
- Leung D, Soter N. Cellular and immunologic mechanisms in atopic dermatitis. J Am Acad Dermatol. 2001;44(suppl):S1-S12.
- US Food and Drug Administration. Briefing document on safety. Omalizumab (Xolair) (recombinant humanized monoclonal antibody to IgE) for treatment of allergic asthma. http://www.fda.gov/ohrms/dockets/ac/03/briefing/3952B1_02_FDA-Xolair-Safety.pdf. Published April 18, 2003. Accessed June 23, 2014.
- Lane JE, Cheyney JM, Lane TN, et al. Treatment of recalcitrant atopic dermatitis with omalizumab. J Am Acad Dermatol. 2006;54:68-72.
- Caruso C, Gaeta F, Valluzzi RL, et al. Omalizumab efficacy in a girl with atopic eczema. Allergy. 2010;65:278-279.
- Krathen RA, Hsu S. Failure of omalizumab for the treatment of severe atopic dermatitis. J Am Dermatol. 2005;53:338-340.
- Fernández-Antón Martínez MC, Leis-Dosil V, Alfageme-Roldán F, et al. Omalizumab for the treatment of Atopic Dermatitis. Actas Dermosifiliogr. 2012;103:624-628.
- Pelaia G, Gallelli L, Romeo P, et al. Omalizumab decreases exacerbation frequency, oral intake of corticosteroids and peripheral blood eosinophils in atopic patients with uncontrolled asthma. Int J Clin Pharmacol Ther. 2011;49:713-721.
- Belloni B, Ziai M, Lim A, et al. Low-dose anti-IgE therapy in patients with atopic eczema with high serum IgE levels. J Allergy Clin Immunol. 2007;120:1223-1225.
- Park SY, Choi MR, Na JI, et al. Recalcitrant atopic dermatitis treated with omalizumab. Ann Dermatol. 2010;22:349-352.
- Velling P, Skowasch D, Pabst S. Improvement of quality of life in patients with concomitant allergic asthma and atopic dermatitis: one year follow-up of omalizumab therapy. Eur J Med Res. 2011;15:407-410.
- Amrol D. Anti-immunoglobulin E in the treatment of refractory atopic dermatitis. South Med J. 2010;103:554-558.
- Heil PM, Maurer D, Klein B, et al. Omalizumab therapy in atopic dermatitis: depletion of IgE does not improve the clinical course-a randomized, placebo-controlled and double blind study. J Dtsch Dermatol Ges. 2010;8:990-998.
- Ramírez del Pozo ME, Contreras Contreras E, López Tiro J, et al. Omalizumab (anti-IgE antibody) in the treatment of severe atopic dermatitis. J Investig Allergol Clin Immunol. 2011;21:416-417.
- Toledo F, Silvestre JF, Muñoz C. Combined therapy with low-dose omalizumab and intravenous immunoglobulin for severe atopic dermatitis: report of four cases. J Eur Acad Dermatol Venereol. 2012;26:1325-1327.
- Sheinkopf LE, Rafi AW, Katz RM. Efficacy of omalizumab in the treatment of atopic dermatitis: a pilot study. Allergy Asthma Proc. 2008;29:530-537.
- Incorvia C, Pravettoni C, Mauro M, et al. Effectiveness of omalizumab in a patient with severe asthma and atopic dermatitis. Monaldi Arch Chest Dis. 2008:69:78-80.
- Schmitt J, Schäkel K. Omalizumab as a therapeutic option in atopic eczema. Current evidence and potential benefit [in German]. Hautarzt. 2007;58:130-132.
- Thaiwat S, Sangasapaviliya A. Omalizumab treatment in severe atopic dermatitis. Asian Pac J Allergy Immunol. 2011;29:357-360.
- Kopp MV. Omalizumab: anti-IgE therapy in allergy. Curr Allergy Asthma Rep. 2011;11:101-106.
- Vichyanond P. Omalizumab in allergic diseases, a recent review. Asian Pc J Allergy Immunol. 2011;29:209-219.
- Scheinfeld N. Omalizumab. A recombinant humanized monoclonal IgE-blocking antibody. Dermatol Online J. 2005;11:2.
- Lowe PJ, Georgiou P, Canvin J. Revision of omalizumab dosing table for dosing every 4 instead of 2 weeks for specific ranges of bodyweight and baseline IgE [published online ahead of print December 8, 2014]. Regul Toxicol Pharmacol. 2015;71:68-77.
- Vigo PG, Girgis KR, Pfuetze BL, et al. Efficacy of anti-IgE therapy in patients with atopic dermatitis. J Am Acad Dermatol. 2006;55:168-170.
- Hanifin J, Chan S. Biochemical and immunologic mechanisms in atopic dermatitis: new targets for emerging therapies. J Am Acad Dermatol. 1999;41:72-77.
Practice Points
- Omalizumab can be effective in treating patients with severe recalcitrant atopic dermatitis with markedly elevated serum IgE.
- Omalizumab appears most effective when used in combination with conventional therapies.
Nitrous oxide linked to less pain in tattoo removal
SAN DIEGO – The results of a small, single-site study suggest that nitrous oxide (NO) can play a significant role in reducing pain during laser tattoo removal.
“Nitrous oxide is a safe and effective option for patients, particularly those who have large tattoos that can’t be adequately numbed with injections or topical numbing,” the study’s lead author, Jared Mallalieu, DO, said in an interview. “NO has allowed us to treat larger tattoos – full sleeve or large back tattoos – in a single setting, which has made treatment more convenient for patients.”
Patients fared better on pain measures when they received NO, compared with topical and injectable anesthetics, according to Dr. Mallalieu, a cosmetic surgeon at the Laser Center of Maryland, Severna Park. The results were so dramatic that EMLA cream is now rarely used for patients in his clinic, although injectable lidocaine is used on smaller tattoos (smaller than 5 inches by 5 inches), he said.
The use of NO comes with challenges, however, in terms of the extra time and patient monitoring required, he said.
Dr. Mallalieu and his associates reported the results in an e-poster at the annual meeting of the American Society for Laser Medicine and Surgery.
Laser tattoo removal can be an agonizing process. “Patients describe it as being significantly more painful than getting a tattoo,” Dr. Mallalieu said. “The intense pain only lasts during the treatment,” he said, “though many patients will note some discomfort for a few hours after a treatment session.”
Most clinics use a topical cream, such as lidocaine/prilocaine (EMLA) or topical benzocaine/lidocaine/tetracaine (BLT), as an anesthetic for these procedures. “Our center has also used 1% lidocaine with epinephrine in small doses of up to 7 mg/kg,” he said. “The injections are much better than the cream.”
Sometimes the clinic uses a device that blows cold air on the skin, which “helps a little,” he added.
For the study, conducted in 2014, 23 laser tattoo removal patients were surveyed about their pain levels using a 1-10 scale, after undergoing a total of 41 single-location procedures.
The average pain rating during the procedure was 9.1 for those treated only with lidocaine/prilocaine, 5.4 for injections of lidocaine with epinephrine alone, and 6.8 for both lidocaine/prilocaine and lidocaine with epinephrine injections.
The average pain rating for NO alone was 2.6, and was 3.6 for those who received both the injection treatment and lidocaine/prilocaine. Three of 12 NO patients reported anxiety.
Another benefit is that patients can drive after receiving NO, unlike other anesthetics, which leave patients sedated, he said. “Levels of NO are titrated to keep the patient sedated, but breathing on their own,” and patients can be easily woken up within moments of stopping the NO.
However, the use of NO requires more time to set up and more monitoring, he added. The average treatment time for procedures with NO was 27 minutes compared with 4 minutes for the other procedure, and “the patient is put on a monitor that measures pulse rate and oxygenation levels,” which not only takes more time, but requires additional staff to watch the patient. “Also, it takes about 3-5 minutes to slowly the titrate the NO to a perfect level.”
The study points out that physicians at the clinic are the only ones who perform the procedures that use NO, but at many clinics, nonphysicians perform tattoo removals.
As for cost, “NO and oxygen tanks are rather inexpensive to purchase and maintain, and there are various small units which serve to titrate the gas,” Dr. Mallalieu said. “We do charge our patients a small fee because of the added personnel and time cost associated with the procedure. As tattoo removal is considered a cosmetic procedure, insurance doesn’t come into play.”
Training to administer NO brings up the issue of what is allowed in the state, he said. Physicians can give sedation to patients, “but some states may limit the degree to which a patient can be sedated in an office. If the physician has a certified operating room, this is not a problem,” he added. “Because dentists commonly use NO, we followed the American Dental Association guidelines ... As we employ an anesthesiologist, we were quite familiar with it. That said, the administration of NO is not complex and [is] easily mastered.”
Dr. Mallalieu reported no relevant disclosures.
SAN DIEGO – The results of a small, single-site study suggest that nitrous oxide (NO) can play a significant role in reducing pain during laser tattoo removal.
“Nitrous oxide is a safe and effective option for patients, particularly those who have large tattoos that can’t be adequately numbed with injections or topical numbing,” the study’s lead author, Jared Mallalieu, DO, said in an interview. “NO has allowed us to treat larger tattoos – full sleeve or large back tattoos – in a single setting, which has made treatment more convenient for patients.”
Patients fared better on pain measures when they received NO, compared with topical and injectable anesthetics, according to Dr. Mallalieu, a cosmetic surgeon at the Laser Center of Maryland, Severna Park. The results were so dramatic that EMLA cream is now rarely used for patients in his clinic, although injectable lidocaine is used on smaller tattoos (smaller than 5 inches by 5 inches), he said.
The use of NO comes with challenges, however, in terms of the extra time and patient monitoring required, he said.
Dr. Mallalieu and his associates reported the results in an e-poster at the annual meeting of the American Society for Laser Medicine and Surgery.
Laser tattoo removal can be an agonizing process. “Patients describe it as being significantly more painful than getting a tattoo,” Dr. Mallalieu said. “The intense pain only lasts during the treatment,” he said, “though many patients will note some discomfort for a few hours after a treatment session.”
Most clinics use a topical cream, such as lidocaine/prilocaine (EMLA) or topical benzocaine/lidocaine/tetracaine (BLT), as an anesthetic for these procedures. “Our center has also used 1% lidocaine with epinephrine in small doses of up to 7 mg/kg,” he said. “The injections are much better than the cream.”
Sometimes the clinic uses a device that blows cold air on the skin, which “helps a little,” he added.
For the study, conducted in 2014, 23 laser tattoo removal patients were surveyed about their pain levels using a 1-10 scale, after undergoing a total of 41 single-location procedures.
The average pain rating during the procedure was 9.1 for those treated only with lidocaine/prilocaine, 5.4 for injections of lidocaine with epinephrine alone, and 6.8 for both lidocaine/prilocaine and lidocaine with epinephrine injections.
The average pain rating for NO alone was 2.6, and was 3.6 for those who received both the injection treatment and lidocaine/prilocaine. Three of 12 NO patients reported anxiety.
Another benefit is that patients can drive after receiving NO, unlike other anesthetics, which leave patients sedated, he said. “Levels of NO are titrated to keep the patient sedated, but breathing on their own,” and patients can be easily woken up within moments of stopping the NO.
However, the use of NO requires more time to set up and more monitoring, he added. The average treatment time for procedures with NO was 27 minutes compared with 4 minutes for the other procedure, and “the patient is put on a monitor that measures pulse rate and oxygenation levels,” which not only takes more time, but requires additional staff to watch the patient. “Also, it takes about 3-5 minutes to slowly the titrate the NO to a perfect level.”
The study points out that physicians at the clinic are the only ones who perform the procedures that use NO, but at many clinics, nonphysicians perform tattoo removals.
As for cost, “NO and oxygen tanks are rather inexpensive to purchase and maintain, and there are various small units which serve to titrate the gas,” Dr. Mallalieu said. “We do charge our patients a small fee because of the added personnel and time cost associated with the procedure. As tattoo removal is considered a cosmetic procedure, insurance doesn’t come into play.”
Training to administer NO brings up the issue of what is allowed in the state, he said. Physicians can give sedation to patients, “but some states may limit the degree to which a patient can be sedated in an office. If the physician has a certified operating room, this is not a problem,” he added. “Because dentists commonly use NO, we followed the American Dental Association guidelines ... As we employ an anesthesiologist, we were quite familiar with it. That said, the administration of NO is not complex and [is] easily mastered.”
Dr. Mallalieu reported no relevant disclosures.
SAN DIEGO – The results of a small, single-site study suggest that nitrous oxide (NO) can play a significant role in reducing pain during laser tattoo removal.
“Nitrous oxide is a safe and effective option for patients, particularly those who have large tattoos that can’t be adequately numbed with injections or topical numbing,” the study’s lead author, Jared Mallalieu, DO, said in an interview. “NO has allowed us to treat larger tattoos – full sleeve or large back tattoos – in a single setting, which has made treatment more convenient for patients.”
Patients fared better on pain measures when they received NO, compared with topical and injectable anesthetics, according to Dr. Mallalieu, a cosmetic surgeon at the Laser Center of Maryland, Severna Park. The results were so dramatic that EMLA cream is now rarely used for patients in his clinic, although injectable lidocaine is used on smaller tattoos (smaller than 5 inches by 5 inches), he said.
The use of NO comes with challenges, however, in terms of the extra time and patient monitoring required, he said.
Dr. Mallalieu and his associates reported the results in an e-poster at the annual meeting of the American Society for Laser Medicine and Surgery.
Laser tattoo removal can be an agonizing process. “Patients describe it as being significantly more painful than getting a tattoo,” Dr. Mallalieu said. “The intense pain only lasts during the treatment,” he said, “though many patients will note some discomfort for a few hours after a treatment session.”
Most clinics use a topical cream, such as lidocaine/prilocaine (EMLA) or topical benzocaine/lidocaine/tetracaine (BLT), as an anesthetic for these procedures. “Our center has also used 1% lidocaine with epinephrine in small doses of up to 7 mg/kg,” he said. “The injections are much better than the cream.”
Sometimes the clinic uses a device that blows cold air on the skin, which “helps a little,” he added.
For the study, conducted in 2014, 23 laser tattoo removal patients were surveyed about their pain levels using a 1-10 scale, after undergoing a total of 41 single-location procedures.
The average pain rating during the procedure was 9.1 for those treated only with lidocaine/prilocaine, 5.4 for injections of lidocaine with epinephrine alone, and 6.8 for both lidocaine/prilocaine and lidocaine with epinephrine injections.
The average pain rating for NO alone was 2.6, and was 3.6 for those who received both the injection treatment and lidocaine/prilocaine. Three of 12 NO patients reported anxiety.
Another benefit is that patients can drive after receiving NO, unlike other anesthetics, which leave patients sedated, he said. “Levels of NO are titrated to keep the patient sedated, but breathing on their own,” and patients can be easily woken up within moments of stopping the NO.
However, the use of NO requires more time to set up and more monitoring, he added. The average treatment time for procedures with NO was 27 minutes compared with 4 minutes for the other procedure, and “the patient is put on a monitor that measures pulse rate and oxygenation levels,” which not only takes more time, but requires additional staff to watch the patient. “Also, it takes about 3-5 minutes to slowly the titrate the NO to a perfect level.”
The study points out that physicians at the clinic are the only ones who perform the procedures that use NO, but at many clinics, nonphysicians perform tattoo removals.
As for cost, “NO and oxygen tanks are rather inexpensive to purchase and maintain, and there are various small units which serve to titrate the gas,” Dr. Mallalieu said. “We do charge our patients a small fee because of the added personnel and time cost associated with the procedure. As tattoo removal is considered a cosmetic procedure, insurance doesn’t come into play.”
Training to administer NO brings up the issue of what is allowed in the state, he said. Physicians can give sedation to patients, “but some states may limit the degree to which a patient can be sedated in an office. If the physician has a certified operating room, this is not a problem,” he added. “Because dentists commonly use NO, we followed the American Dental Association guidelines ... As we employ an anesthesiologist, we were quite familiar with it. That said, the administration of NO is not complex and [is] easily mastered.”
Dr. Mallalieu reported no relevant disclosures.
Thousands expected to get CAR T-cells by 2018
NEW YORK – Should the first chimeric antigen receptor (CAR) T-cell treatment receive Food and Drug Administration approval for refractory, aggressive non-Hodgkin lymphoma, possibly before the end of 2017, several thousand U.S. patients will be potential candidates for the treatment, Jeremy S. Abramson, MD, predicted at a conference held by Imedex.
Dr. Abramson has led studies using a CAR T cell that differs from the one furthest along in development. He based his predicted timetable for an approved biologics license of the process, with which he can engineer patient-specific T cells that are under development by Kite Pharma, on the “remarkable” level of complete responses the intervention produced in a pivotal phase II study.
“Seeing a complete response rate of close to 40% that is sustained for more than 3 months and a complete response rate of close to a third at 6 months is light years beyond what is now available for patients” with these chemotherapy refractory B-cell lymphomas, said Dr. Abramson, clinical director of the Center for Lymphoma at Massachusetts General Hospital in Boston. “This is the first treatment to show a significant impact on large B-cell lymphoma, and that makes me optimistic” that the FDA will grant license approval later in 2017, he said in an interview.
Dr. Abramson acknowledged that some patients developed grade 3 or 4 cytokine-release syndrome and neurologic events, but the events were reversible and manageable if treated with the immunosuppressant tocilizumab (Actemra) or a corticosteroid.
At the end of March, Kite reported the completion of its FDA application, and, on April 2, the ZUMA-1 investigators presented an updated report on their results, with a 36% complete response rate across all enrolled patients at 6 month follow-up and a 39% complete response rate in all patients out to a median follow-up of 8.7 months.
Annually, in U.S. practice, perhaps 3,000 new patients with diffuse large B-cell lymphoma would meet the enrollment criteria for ZUMA-1, Dr. Abramson estimated. Once axicabtagene ciloleucel becomes commercially available in the United States, several thousand U.S. patients might initially seek the treatment.
Dr. Abramson has been a consultant to Kite Pharma and to AbbVie, Genentech, Gilead, and Seattle Genetics.
[email protected]
On Twitter @mitchelzoler
NEW YORK – Should the first chimeric antigen receptor (CAR) T-cell treatment receive Food and Drug Administration approval for refractory, aggressive non-Hodgkin lymphoma, possibly before the end of 2017, several thousand U.S. patients will be potential candidates for the treatment, Jeremy S. Abramson, MD, predicted at a conference held by Imedex.
Dr. Abramson has led studies using a CAR T cell that differs from the one furthest along in development. He based his predicted timetable for an approved biologics license of the process, with which he can engineer patient-specific T cells that are under development by Kite Pharma, on the “remarkable” level of complete responses the intervention produced in a pivotal phase II study.
“Seeing a complete response rate of close to 40% that is sustained for more than 3 months and a complete response rate of close to a third at 6 months is light years beyond what is now available for patients” with these chemotherapy refractory B-cell lymphomas, said Dr. Abramson, clinical director of the Center for Lymphoma at Massachusetts General Hospital in Boston. “This is the first treatment to show a significant impact on large B-cell lymphoma, and that makes me optimistic” that the FDA will grant license approval later in 2017, he said in an interview.
Dr. Abramson acknowledged that some patients developed grade 3 or 4 cytokine-release syndrome and neurologic events, but the events were reversible and manageable if treated with the immunosuppressant tocilizumab (Actemra) or a corticosteroid.
At the end of March, Kite reported the completion of its FDA application, and, on April 2, the ZUMA-1 investigators presented an updated report on their results, with a 36% complete response rate across all enrolled patients at 6 month follow-up and a 39% complete response rate in all patients out to a median follow-up of 8.7 months.
Annually, in U.S. practice, perhaps 3,000 new patients with diffuse large B-cell lymphoma would meet the enrollment criteria for ZUMA-1, Dr. Abramson estimated. Once axicabtagene ciloleucel becomes commercially available in the United States, several thousand U.S. patients might initially seek the treatment.
Dr. Abramson has been a consultant to Kite Pharma and to AbbVie, Genentech, Gilead, and Seattle Genetics.
[email protected]
On Twitter @mitchelzoler
NEW YORK – Should the first chimeric antigen receptor (CAR) T-cell treatment receive Food and Drug Administration approval for refractory, aggressive non-Hodgkin lymphoma, possibly before the end of 2017, several thousand U.S. patients will be potential candidates for the treatment, Jeremy S. Abramson, MD, predicted at a conference held by Imedex.
Dr. Abramson has led studies using a CAR T cell that differs from the one furthest along in development. He based his predicted timetable for an approved biologics license of the process, with which he can engineer patient-specific T cells that are under development by Kite Pharma, on the “remarkable” level of complete responses the intervention produced in a pivotal phase II study.
“Seeing a complete response rate of close to 40% that is sustained for more than 3 months and a complete response rate of close to a third at 6 months is light years beyond what is now available for patients” with these chemotherapy refractory B-cell lymphomas, said Dr. Abramson, clinical director of the Center for Lymphoma at Massachusetts General Hospital in Boston. “This is the first treatment to show a significant impact on large B-cell lymphoma, and that makes me optimistic” that the FDA will grant license approval later in 2017, he said in an interview.
Dr. Abramson acknowledged that some patients developed grade 3 or 4 cytokine-release syndrome and neurologic events, but the events were reversible and manageable if treated with the immunosuppressant tocilizumab (Actemra) or a corticosteroid.
At the end of March, Kite reported the completion of its FDA application, and, on April 2, the ZUMA-1 investigators presented an updated report on their results, with a 36% complete response rate across all enrolled patients at 6 month follow-up and a 39% complete response rate in all patients out to a median follow-up of 8.7 months.
Annually, in U.S. practice, perhaps 3,000 new patients with diffuse large B-cell lymphoma would meet the enrollment criteria for ZUMA-1, Dr. Abramson estimated. Once axicabtagene ciloleucel becomes commercially available in the United States, several thousand U.S. patients might initially seek the treatment.
Dr. Abramson has been a consultant to Kite Pharma and to AbbVie, Genentech, Gilead, and Seattle Genetics.
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM A MEETING ON HEMATOLOGIC MALIGNANCIES
Study finds psoriasis link to melanoma and hematologic cancers
Patients with psoriasis may be at a greater risk of melanoma and hematologic cancers, compared with the general population, but treatments do not appear to increase risk, according to Shivani P. Reddy of the University of Illinois at Chicago, and associates.
In a retrospective cohort study, they identified 815,765 patients at Kaiser Permanente Southern California who had at least one medical encounter from January 2004 through December 2013. Of these patients, 8,161 (1%) met the diagnostic and inclusion criteria for psoriasis, and there were 7,167 (0.89%) cases of melanoma and 5,399 (0.66%) cases of lymphoma or leukemia.
Among the patients with psoriasis, there were 62 (0.87%) melanoma cases and 47 (0.87%) cases of lymphoma or leukemia.
Of the 109 patients with psoriasis who went on to develop melanoma or lymphoma, the time to diagnosis of melanoma or hematologic cancers was significantly less for patients with psoriasis than for patients without psoriasis (P = .01). The patients with psoriasis had a 1.53 times higher risk of developing a malignancy compared with patients without psoriasis (P less than .01) in the multivariable Cox proportional hazards model.
“There were no differences between patients with melanoma and hematologic cancer by treatment type,” which were phototherapy, tumor necrosis factor inhibitor therapy, and topical medications, they wrote.
“Our study demonstrates that the risk of hematologic cancer and melanoma is increased in patients with psoriasis over time, although this risk is not impacted by psoriasis therapies,” the researchers concluded. “Defining the risk of malignancy in these patients is important for proper workup and management.”
Read the study in the Journal of the American Academy of Dermatology (doi: 10.1016/j.jaad.2016.09.047).
Patients with psoriasis may be at a greater risk of melanoma and hematologic cancers, compared with the general population, but treatments do not appear to increase risk, according to Shivani P. Reddy of the University of Illinois at Chicago, and associates.
In a retrospective cohort study, they identified 815,765 patients at Kaiser Permanente Southern California who had at least one medical encounter from January 2004 through December 2013. Of these patients, 8,161 (1%) met the diagnostic and inclusion criteria for psoriasis, and there were 7,167 (0.89%) cases of melanoma and 5,399 (0.66%) cases of lymphoma or leukemia.
Among the patients with psoriasis, there were 62 (0.87%) melanoma cases and 47 (0.87%) cases of lymphoma or leukemia.
Of the 109 patients with psoriasis who went on to develop melanoma or lymphoma, the time to diagnosis of melanoma or hematologic cancers was significantly less for patients with psoriasis than for patients without psoriasis (P = .01). The patients with psoriasis had a 1.53 times higher risk of developing a malignancy compared with patients without psoriasis (P less than .01) in the multivariable Cox proportional hazards model.
“There were no differences between patients with melanoma and hematologic cancer by treatment type,” which were phototherapy, tumor necrosis factor inhibitor therapy, and topical medications, they wrote.
“Our study demonstrates that the risk of hematologic cancer and melanoma is increased in patients with psoriasis over time, although this risk is not impacted by psoriasis therapies,” the researchers concluded. “Defining the risk of malignancy in these patients is important for proper workup and management.”
Read the study in the Journal of the American Academy of Dermatology (doi: 10.1016/j.jaad.2016.09.047).
Patients with psoriasis may be at a greater risk of melanoma and hematologic cancers, compared with the general population, but treatments do not appear to increase risk, according to Shivani P. Reddy of the University of Illinois at Chicago, and associates.
In a retrospective cohort study, they identified 815,765 patients at Kaiser Permanente Southern California who had at least one medical encounter from January 2004 through December 2013. Of these patients, 8,161 (1%) met the diagnostic and inclusion criteria for psoriasis, and there were 7,167 (0.89%) cases of melanoma and 5,399 (0.66%) cases of lymphoma or leukemia.
Among the patients with psoriasis, there were 62 (0.87%) melanoma cases and 47 (0.87%) cases of lymphoma or leukemia.
Of the 109 patients with psoriasis who went on to develop melanoma or lymphoma, the time to diagnosis of melanoma or hematologic cancers was significantly less for patients with psoriasis than for patients without psoriasis (P = .01). The patients with psoriasis had a 1.53 times higher risk of developing a malignancy compared with patients without psoriasis (P less than .01) in the multivariable Cox proportional hazards model.
“There were no differences between patients with melanoma and hematologic cancer by treatment type,” which were phototherapy, tumor necrosis factor inhibitor therapy, and topical medications, they wrote.
“Our study demonstrates that the risk of hematologic cancer and melanoma is increased in patients with psoriasis over time, although this risk is not impacted by psoriasis therapies,” the researchers concluded. “Defining the risk of malignancy in these patients is important for proper workup and management.”
Read the study in the Journal of the American Academy of Dermatology (doi: 10.1016/j.jaad.2016.09.047).
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Time to reexamine surgery for nonlocalized bronchiectasis
Nonlocalized bronchiectasis is becoming more common in developing countries and has been difficult to treat. While surgery for localized bronchiectasis has been proven, its role in nonlocalized disease is less established; researchers from China are advocating for a reexamination of surgical resection in this disease based on results of a small cohort study at their academic center.
“Lobectomy for the predominant lesion is a safe procedure in the surgical treatment of nonlocalized bronchiectasis and leads to significant relief of symptoms with good rates of satisfaction,” Jie Dai, PhD, of Shanghai (China) Pulmonary Hospital Tongji University and his coauthors reported in the Journal of Thoracic and Cardiovascular Surgery (2017 Apr;153:979-85).
The researchers reviewed the medical records of 37 consecutive patients – 10 men and 27 women – with nonlocalized bronchiectasis who had lobectomies via thoracotomies during 2010-2013. Twenty-three patients (62.2%) were symptom free after surgery and 10 (27%) reported that their symptoms had improved. Four (10.8%) said their symptoms either did not improve or worsened, but three of them also had chronic occlusive pulmonary disease. There were no deaths, and the morbidity rate was 21.6%.
The researchers used three criteria to select candidates for surgery: persistent symptoms despite medical treatment; an identifiable predominant lesion; and cardiopulmonary function compatible with anesthetic risk. Average age was 54.5 years and more than half (19) had no smoking history.
The surgical technique involved a posterolateral thoracotomy and a double-lumen endotracheal tube to avoid contamination of the opposite side of the lung during surgery. Surgery avoided excessive bronchial dissection and preserved peribronchial tissues. Extrapleural dissection avoided spillage of lung contents into the pleural space.
Treatment of the hilum followed an order from the pulmonary artery to the pulmonary vein and then to the bronchus. An ultrasonic device helped isolate and then ligate or sever distorted bronchial arteries. A mechanical stapler was used to close the bronchial stump. Reinforcement involved an intercostal muscle flap in 16 cases and a pedicled parietal pleural flap in 21. If any sign of pleural infection appeared after hemostasis, pleural space irrigation with 0.5% neomycin (500 mg/L) was initiated. Two chest drains were placed at the bronchial stump, and the bronchial suture checked with bronchoscopy. Airway secretions were removed, and pathology confirmed bronchiectasis all specimens.
The frequency of acute infection and hemoptysis decreased significantly at 1 year postoperatively, from 5.3% to 1.8% and 4.9% to 1.1%, respectively, (P less than .01 for both). Daily sputum volume decreased an average of 26.3 mL (P less than .01) and sputum cultures became sterile in 13 (35%) of patients (P less than .01).
Previously, surgery for nonlocalized bronchiectasis had been reserved for life-threatening symptoms only, but Dr. Dai and his coauthors fashioned their study on previous studies of lobectomy that included patients with nonlocalized bronchiectasis (Br J Surg. 2005;92:836-9; Ann Thorac Surg. 2003;75:382-7).
Two major complications occurred in the Shanghai cohort: empyema and persistent air leak, both of which were managed without a reoperation and had been reported in previous series. Dr. Dai and his coauthors have adopted protocols to reduce complications, among them, requiring that patients have sputum output greater than 20 mL/day with little purulence and no engorgement or edema in the tunica mucosa bronchiorum on bronchoscopy.
But the researchers are not ready to extend surgery as a blanket indication for nonlocalized bronchiectasis. “It is worth mentioning that the surgical benefit is limited to patients who have only one predominant area of bronchiectatic disease that can be localized by CT instead of those with diffuse bronchiectasis,” they wrote. “The ideal surgical candidate has a heterogeneous distribution of diseased areas.”
The investigators pointed out that the study was limited by its small size and lack of information on etiologies of disease.
Dr. Dai and his coauthors had no financial relationships to disclose.
The study by Dr. Dai and his coauthors “is an important contribution to the literature” despite its limitations, Steven Milman, MD, and Thomas Ng, MD, of Brown University, Providence, R.I., said in their invited commentary (J Thorac Cardiovasc Surg. 2017 Apr;153:986). However, they added, “Several important points need to be stressed.”
Among those points: The researchers studied a “highly selected group” of young patients with good pulmonary functions; mean follow-up was short (15 months); the etiology of bronchiectasis was unknown; and lobectomy was not the optimal treatment for nonlocalized bronchiectasis. “It must be remembered that these patients first failed medical therapy and that the study population received lobectomy due to the extent of the dominant disease and not as routine treatment,” Dr. Milman and Dr. Ng wrote.
To validate the findings, Dr. Milman and Dr. Ng said, not only do more patients need to be studied with longer follow-up but future investigators also should study minimally invasive approaches to see if that would improve the outcomes.
Dr. Milman and Dr. Ng had no financial relationships to disclose.
The study by Dr. Dai and his coauthors “is an important contribution to the literature” despite its limitations, Steven Milman, MD, and Thomas Ng, MD, of Brown University, Providence, R.I., said in their invited commentary (J Thorac Cardiovasc Surg. 2017 Apr;153:986). However, they added, “Several important points need to be stressed.”
Among those points: The researchers studied a “highly selected group” of young patients with good pulmonary functions; mean follow-up was short (15 months); the etiology of bronchiectasis was unknown; and lobectomy was not the optimal treatment for nonlocalized bronchiectasis. “It must be remembered that these patients first failed medical therapy and that the study population received lobectomy due to the extent of the dominant disease and not as routine treatment,” Dr. Milman and Dr. Ng wrote.
To validate the findings, Dr. Milman and Dr. Ng said, not only do more patients need to be studied with longer follow-up but future investigators also should study minimally invasive approaches to see if that would improve the outcomes.
Dr. Milman and Dr. Ng had no financial relationships to disclose.
The study by Dr. Dai and his coauthors “is an important contribution to the literature” despite its limitations, Steven Milman, MD, and Thomas Ng, MD, of Brown University, Providence, R.I., said in their invited commentary (J Thorac Cardiovasc Surg. 2017 Apr;153:986). However, they added, “Several important points need to be stressed.”
Among those points: The researchers studied a “highly selected group” of young patients with good pulmonary functions; mean follow-up was short (15 months); the etiology of bronchiectasis was unknown; and lobectomy was not the optimal treatment for nonlocalized bronchiectasis. “It must be remembered that these patients first failed medical therapy and that the study population received lobectomy due to the extent of the dominant disease and not as routine treatment,” Dr. Milman and Dr. Ng wrote.
To validate the findings, Dr. Milman and Dr. Ng said, not only do more patients need to be studied with longer follow-up but future investigators also should study minimally invasive approaches to see if that would improve the outcomes.
Dr. Milman and Dr. Ng had no financial relationships to disclose.
Nonlocalized bronchiectasis is becoming more common in developing countries and has been difficult to treat. While surgery for localized bronchiectasis has been proven, its role in nonlocalized disease is less established; researchers from China are advocating for a reexamination of surgical resection in this disease based on results of a small cohort study at their academic center.
“Lobectomy for the predominant lesion is a safe procedure in the surgical treatment of nonlocalized bronchiectasis and leads to significant relief of symptoms with good rates of satisfaction,” Jie Dai, PhD, of Shanghai (China) Pulmonary Hospital Tongji University and his coauthors reported in the Journal of Thoracic and Cardiovascular Surgery (2017 Apr;153:979-85).
The researchers reviewed the medical records of 37 consecutive patients – 10 men and 27 women – with nonlocalized bronchiectasis who had lobectomies via thoracotomies during 2010-2013. Twenty-three patients (62.2%) were symptom free after surgery and 10 (27%) reported that their symptoms had improved. Four (10.8%) said their symptoms either did not improve or worsened, but three of them also had chronic occlusive pulmonary disease. There were no deaths, and the morbidity rate was 21.6%.
The researchers used three criteria to select candidates for surgery: persistent symptoms despite medical treatment; an identifiable predominant lesion; and cardiopulmonary function compatible with anesthetic risk. Average age was 54.5 years and more than half (19) had no smoking history.
The surgical technique involved a posterolateral thoracotomy and a double-lumen endotracheal tube to avoid contamination of the opposite side of the lung during surgery. Surgery avoided excessive bronchial dissection and preserved peribronchial tissues. Extrapleural dissection avoided spillage of lung contents into the pleural space.
Treatment of the hilum followed an order from the pulmonary artery to the pulmonary vein and then to the bronchus. An ultrasonic device helped isolate and then ligate or sever distorted bronchial arteries. A mechanical stapler was used to close the bronchial stump. Reinforcement involved an intercostal muscle flap in 16 cases and a pedicled parietal pleural flap in 21. If any sign of pleural infection appeared after hemostasis, pleural space irrigation with 0.5% neomycin (500 mg/L) was initiated. Two chest drains were placed at the bronchial stump, and the bronchial suture checked with bronchoscopy. Airway secretions were removed, and pathology confirmed bronchiectasis all specimens.
The frequency of acute infection and hemoptysis decreased significantly at 1 year postoperatively, from 5.3% to 1.8% and 4.9% to 1.1%, respectively, (P less than .01 for both). Daily sputum volume decreased an average of 26.3 mL (P less than .01) and sputum cultures became sterile in 13 (35%) of patients (P less than .01).
Previously, surgery for nonlocalized bronchiectasis had been reserved for life-threatening symptoms only, but Dr. Dai and his coauthors fashioned their study on previous studies of lobectomy that included patients with nonlocalized bronchiectasis (Br J Surg. 2005;92:836-9; Ann Thorac Surg. 2003;75:382-7).
Two major complications occurred in the Shanghai cohort: empyema and persistent air leak, both of which were managed without a reoperation and had been reported in previous series. Dr. Dai and his coauthors have adopted protocols to reduce complications, among them, requiring that patients have sputum output greater than 20 mL/day with little purulence and no engorgement or edema in the tunica mucosa bronchiorum on bronchoscopy.
But the researchers are not ready to extend surgery as a blanket indication for nonlocalized bronchiectasis. “It is worth mentioning that the surgical benefit is limited to patients who have only one predominant area of bronchiectatic disease that can be localized by CT instead of those with diffuse bronchiectasis,” they wrote. “The ideal surgical candidate has a heterogeneous distribution of diseased areas.”
The investigators pointed out that the study was limited by its small size and lack of information on etiologies of disease.
Dr. Dai and his coauthors had no financial relationships to disclose.
Nonlocalized bronchiectasis is becoming more common in developing countries and has been difficult to treat. While surgery for localized bronchiectasis has been proven, its role in nonlocalized disease is less established; researchers from China are advocating for a reexamination of surgical resection in this disease based on results of a small cohort study at their academic center.
“Lobectomy for the predominant lesion is a safe procedure in the surgical treatment of nonlocalized bronchiectasis and leads to significant relief of symptoms with good rates of satisfaction,” Jie Dai, PhD, of Shanghai (China) Pulmonary Hospital Tongji University and his coauthors reported in the Journal of Thoracic and Cardiovascular Surgery (2017 Apr;153:979-85).
The researchers reviewed the medical records of 37 consecutive patients – 10 men and 27 women – with nonlocalized bronchiectasis who had lobectomies via thoracotomies during 2010-2013. Twenty-three patients (62.2%) were symptom free after surgery and 10 (27%) reported that their symptoms had improved. Four (10.8%) said their symptoms either did not improve or worsened, but three of them also had chronic occlusive pulmonary disease. There were no deaths, and the morbidity rate was 21.6%.
The researchers used three criteria to select candidates for surgery: persistent symptoms despite medical treatment; an identifiable predominant lesion; and cardiopulmonary function compatible with anesthetic risk. Average age was 54.5 years and more than half (19) had no smoking history.
The surgical technique involved a posterolateral thoracotomy and a double-lumen endotracheal tube to avoid contamination of the opposite side of the lung during surgery. Surgery avoided excessive bronchial dissection and preserved peribronchial tissues. Extrapleural dissection avoided spillage of lung contents into the pleural space.
Treatment of the hilum followed an order from the pulmonary artery to the pulmonary vein and then to the bronchus. An ultrasonic device helped isolate and then ligate or sever distorted bronchial arteries. A mechanical stapler was used to close the bronchial stump. Reinforcement involved an intercostal muscle flap in 16 cases and a pedicled parietal pleural flap in 21. If any sign of pleural infection appeared after hemostasis, pleural space irrigation with 0.5% neomycin (500 mg/L) was initiated. Two chest drains were placed at the bronchial stump, and the bronchial suture checked with bronchoscopy. Airway secretions were removed, and pathology confirmed bronchiectasis all specimens.
The frequency of acute infection and hemoptysis decreased significantly at 1 year postoperatively, from 5.3% to 1.8% and 4.9% to 1.1%, respectively, (P less than .01 for both). Daily sputum volume decreased an average of 26.3 mL (P less than .01) and sputum cultures became sterile in 13 (35%) of patients (P less than .01).
Previously, surgery for nonlocalized bronchiectasis had been reserved for life-threatening symptoms only, but Dr. Dai and his coauthors fashioned their study on previous studies of lobectomy that included patients with nonlocalized bronchiectasis (Br J Surg. 2005;92:836-9; Ann Thorac Surg. 2003;75:382-7).
Two major complications occurred in the Shanghai cohort: empyema and persistent air leak, both of which were managed without a reoperation and had been reported in previous series. Dr. Dai and his coauthors have adopted protocols to reduce complications, among them, requiring that patients have sputum output greater than 20 mL/day with little purulence and no engorgement or edema in the tunica mucosa bronchiorum on bronchoscopy.
But the researchers are not ready to extend surgery as a blanket indication for nonlocalized bronchiectasis. “It is worth mentioning that the surgical benefit is limited to patients who have only one predominant area of bronchiectatic disease that can be localized by CT instead of those with diffuse bronchiectasis,” they wrote. “The ideal surgical candidate has a heterogeneous distribution of diseased areas.”
The investigators pointed out that the study was limited by its small size and lack of information on etiologies of disease.
Dr. Dai and his coauthors had no financial relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Lobectomy for nonlocalized bronchiectasis can improve symptoms significantly.
Major finding: Among 37 patients who had lobectomy, 62.2% were asymptomatic after surgery.
Data source: Single-center retrospective review of 37 patients who had lobectomy for nonlocalized bronchiectasis from January 2010 to December 2013.
Disclosure: Dr. Dai and his coauthors had no financial relationships to disclose.
Eltrombopag improves frequency, speed, robustness of hematologic recovery
Adding the thrombopoietin-receptor agonist eltrombopag to standard immunosuppressive therapy markedly improved the frequency, speed, and robustness of hematologic recovery in a phase I-II trial of patients with severe aplastic anemia, according to a report published online April 20 in the New England Journal of Medicine.
Previously, researchers found that eltrombopag was effective against aplastic anemia that was refractory to immunosuppression, inducing higher platelet counts, hemoglobin levels, and neutrophil numbers when used as a single agent. They then examined whether adding the drug to immunosuppression in treatment-naive patients would improve the response in this nonrandomized prospective trial, said Danielle M. Townsley, MD, of the hematology branch, National Heart, Lung, and Blood Institute, and her associates.
Ninety-two consecutive patients aged 3-82 years were divided into three cohorts with different timing and duration of treatment. Cohort 1 (30 patients) received eltrombopag from day 14 to 6 months; cohort 2 (31 patients) received it from day 14 to 3 months; and cohort 3 (31 patients) received it from day 1 to 6 months.
The primary efficacy endpoint – the rate of complete hematologic response at 6 months – was highest, at 58%, in cohort 3, which had the earliest initiation and the longest duration of eltrombopag treatment. It was lowest, at 26%, in cohort 2, which had the shortest duration of eltrombopag treatment. The rate of complete hematologic response was intermediate in cohort 1, at 33% (N Engl J Med. 2017 Apr 20. doi:10.1056/NEJMoa1613878).
These complete response rates all exceeded those reported historically, which range from 10% to 20%. Moreover, the rate of partial or complete hematologic response was 87% across all three cohorts, compared with the 66% partial or complete response rate that would be expected with standard immunosuppression alone. Absolute neutrophil counts and platelet counts in all three cohorts also were higher at both 3 and 6 months than were those that have been reported historically.
The average time to independence from transfusions in the entire study population was 1 month, and clinically meaningful improvements in neutrophil levels were seen within a few weeks of initiating eltrombopag.
Two cases of severe cutaneous eruptions led to discontinuation of the study drug. Liver abnormalities were frequent but transient and did not limit the use of eltrombopag.
If these results are validated in future studies, and if no unexpected late complications are identified, adding eltrombopag to standard immunosuppressive therapy “may help patients optimize the timing of allogeneic stem-cell transplantation or avoid it. Of particular interest would be use of eltrombopag in combination with less toxic immunosuppressive regimens that omit antithymocyte globulin, particularly in older patients, in patients with coexisting conditions, and in developing countries where aplastic anemia is prevalent and conventional therapies [are] extremely costly,” Dr. Townsley and her associates noted.
One such confirmatory study, a large randomized placebo-controlled trial (NCT02099747), is now underway in Europe, they wrote.
This trial was supported by the National Heart, Lung, and Blood Institute. Dr. Townsley and her associates reported ties to GlaxoSmithKline and Novartis, makers of eltrombopag.
Adding the thrombopoietin-receptor agonist eltrombopag to standard immunosuppressive therapy markedly improved the frequency, speed, and robustness of hematologic recovery in a phase I-II trial of patients with severe aplastic anemia, according to a report published online April 20 in the New England Journal of Medicine.
Previously, researchers found that eltrombopag was effective against aplastic anemia that was refractory to immunosuppression, inducing higher platelet counts, hemoglobin levels, and neutrophil numbers when used as a single agent. They then examined whether adding the drug to immunosuppression in treatment-naive patients would improve the response in this nonrandomized prospective trial, said Danielle M. Townsley, MD, of the hematology branch, National Heart, Lung, and Blood Institute, and her associates.
Ninety-two consecutive patients aged 3-82 years were divided into three cohorts with different timing and duration of treatment. Cohort 1 (30 patients) received eltrombopag from day 14 to 6 months; cohort 2 (31 patients) received it from day 14 to 3 months; and cohort 3 (31 patients) received it from day 1 to 6 months.
The primary efficacy endpoint – the rate of complete hematologic response at 6 months – was highest, at 58%, in cohort 3, which had the earliest initiation and the longest duration of eltrombopag treatment. It was lowest, at 26%, in cohort 2, which had the shortest duration of eltrombopag treatment. The rate of complete hematologic response was intermediate in cohort 1, at 33% (N Engl J Med. 2017 Apr 20. doi:10.1056/NEJMoa1613878).
These complete response rates all exceeded those reported historically, which range from 10% to 20%. Moreover, the rate of partial or complete hematologic response was 87% across all three cohorts, compared with the 66% partial or complete response rate that would be expected with standard immunosuppression alone. Absolute neutrophil counts and platelet counts in all three cohorts also were higher at both 3 and 6 months than were those that have been reported historically.
The average time to independence from transfusions in the entire study population was 1 month, and clinically meaningful improvements in neutrophil levels were seen within a few weeks of initiating eltrombopag.
Two cases of severe cutaneous eruptions led to discontinuation of the study drug. Liver abnormalities were frequent but transient and did not limit the use of eltrombopag.
If these results are validated in future studies, and if no unexpected late complications are identified, adding eltrombopag to standard immunosuppressive therapy “may help patients optimize the timing of allogeneic stem-cell transplantation or avoid it. Of particular interest would be use of eltrombopag in combination with less toxic immunosuppressive regimens that omit antithymocyte globulin, particularly in older patients, in patients with coexisting conditions, and in developing countries where aplastic anemia is prevalent and conventional therapies [are] extremely costly,” Dr. Townsley and her associates noted.
One such confirmatory study, a large randomized placebo-controlled trial (NCT02099747), is now underway in Europe, they wrote.
This trial was supported by the National Heart, Lung, and Blood Institute. Dr. Townsley and her associates reported ties to GlaxoSmithKline and Novartis, makers of eltrombopag.
Adding the thrombopoietin-receptor agonist eltrombopag to standard immunosuppressive therapy markedly improved the frequency, speed, and robustness of hematologic recovery in a phase I-II trial of patients with severe aplastic anemia, according to a report published online April 20 in the New England Journal of Medicine.
Previously, researchers found that eltrombopag was effective against aplastic anemia that was refractory to immunosuppression, inducing higher platelet counts, hemoglobin levels, and neutrophil numbers when used as a single agent. They then examined whether adding the drug to immunosuppression in treatment-naive patients would improve the response in this nonrandomized prospective trial, said Danielle M. Townsley, MD, of the hematology branch, National Heart, Lung, and Blood Institute, and her associates.
Ninety-two consecutive patients aged 3-82 years were divided into three cohorts with different timing and duration of treatment. Cohort 1 (30 patients) received eltrombopag from day 14 to 6 months; cohort 2 (31 patients) received it from day 14 to 3 months; and cohort 3 (31 patients) received it from day 1 to 6 months.
The primary efficacy endpoint – the rate of complete hematologic response at 6 months – was highest, at 58%, in cohort 3, which had the earliest initiation and the longest duration of eltrombopag treatment. It was lowest, at 26%, in cohort 2, which had the shortest duration of eltrombopag treatment. The rate of complete hematologic response was intermediate in cohort 1, at 33% (N Engl J Med. 2017 Apr 20. doi:10.1056/NEJMoa1613878).
These complete response rates all exceeded those reported historically, which range from 10% to 20%. Moreover, the rate of partial or complete hematologic response was 87% across all three cohorts, compared with the 66% partial or complete response rate that would be expected with standard immunosuppression alone. Absolute neutrophil counts and platelet counts in all three cohorts also were higher at both 3 and 6 months than were those that have been reported historically.
The average time to independence from transfusions in the entire study population was 1 month, and clinically meaningful improvements in neutrophil levels were seen within a few weeks of initiating eltrombopag.
Two cases of severe cutaneous eruptions led to discontinuation of the study drug. Liver abnormalities were frequent but transient and did not limit the use of eltrombopag.
If these results are validated in future studies, and if no unexpected late complications are identified, adding eltrombopag to standard immunosuppressive therapy “may help patients optimize the timing of allogeneic stem-cell transplantation or avoid it. Of particular interest would be use of eltrombopag in combination with less toxic immunosuppressive regimens that omit antithymocyte globulin, particularly in older patients, in patients with coexisting conditions, and in developing countries where aplastic anemia is prevalent and conventional therapies [are] extremely costly,” Dr. Townsley and her associates noted.
One such confirmatory study, a large randomized placebo-controlled trial (NCT02099747), is now underway in Europe, they wrote.
This trial was supported by the National Heart, Lung, and Blood Institute. Dr. Townsley and her associates reported ties to GlaxoSmithKline and Novartis, makers of eltrombopag.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Adding eltrombopag to standard immunosuppression markedly improves the frequency, speed, and robustness of hematologic recovery in patients with severe aplastic anemia.
Major finding: The rate of partial or complete hematologic response was 87% across all 3 cohorts, compared with the 66% partial or complete response rate that would be expected with standard immunosuppression alone.
Data source: A prospective phase I-II study involving 92 patients aged 3-82 years who were followed for a median of 2 years.
Disclosures: This trial was supported by the National Heart, Lung, and Blood Institute. Dr. Townsley and her associates reported ties to GlaxoSmithKline and Novartis, makers of eltrombopag.
In Rare Case Colorectal Cancer Causes Thrombus
A 46-year-old woman went to her family doctor after 3 months of abdominal bloating, fatigue, nausea, vomiting, anorexia, and weight loss. Ultrasound imaging revealed hepatic lesions and a mass in the colon; she was diagnosed with colon cancer. The cancer had metastasized to an extent that complete resection wasn’t possible, so she received palliative-intent therapy for the next 18 months.
Related: Colorectal Screening: Available but Underused
Initially, the patient responded to the treatment but then presented to the emergency department (ED) with a severe headache. A CT scan revealed that the cancer had spread to her brain. However, this time resection was possible, and she recovered well.
Three weeks later the patient was back in the ED with an infection. A new CT scan showed no evidence of abscess (one of the differential diagnoses). A transthoracic echocardiogram showed a right atrial lesion, and further imaging confirmed a lesion in the right atrium. “Unexpectedly,” her clinicians reported, the lesion originated from the distal inferior vena cava (IVC): She had shown no signs of symptoms of pulmonary embolus or occlusion of the IVC.
Tumor thrombus is rarely reported with colorectal cancer cases, so the patient’s clinicians at first thought the mass in the IVC was bland thrombus, managed with anticoagulation alone. The clinicians felt that the assumption was reasonable, given the link between malignancy and venous thromboembolism; also because the patient had an indwelling central venous catheter. Contrast-enhanced CT scan and contrast-enhanced ultrasound, however, supported the diagnosis of tumor thrombus.
Due to the rarity of tumor thrombus in colorectal cancer, there are no guidelines for diagnosis and management, the clinicians say. In the patient’s case, consultation with cardiologists, radiologists, and gastrointestinal specialists at the cancer center resulted in an offer to extract the thrombus, but the risks and the fact that she was asymptomatic led the patient to decline. She was instead restarted on palliative chemotherapy with heparin in case part of the thrombus was indeed bland thrombus.
The patient’s condition deteriorated over the next 3 months. She and her team agreed that supportive care at home was best. The patient still had no symptoms from the tumor thrombus when she died.
Related: Cancer Prevention and Gastrointestinal Risk
Autopsy supported the suspicion that the original lesion was partly tumor thrombus and partly bland thrombus, reduced by anticoagulation. But autopsy results revealed no embolization of tumor thrombus or bland thrombus into the pulmonary arteries, although there were extensive metastases in the brain, lung, liver, adrenals, and ovaries. Ultimately, the patient’s death was attributed not to the tumor thrombus that extended into the right atrium but to multiorgan failure due to cancer--validating the decisions to not choose surgery for the thrombus.
Source:
Meyers D, Nixon NA, Franko A, Ng D, Tam VC. BMJ Case Rep. 2017;2017:pii:bcr2016218107.
doi: 10.1136/bcr-2016-218107.
A 46-year-old woman went to her family doctor after 3 months of abdominal bloating, fatigue, nausea, vomiting, anorexia, and weight loss. Ultrasound imaging revealed hepatic lesions and a mass in the colon; she was diagnosed with colon cancer. The cancer had metastasized to an extent that complete resection wasn’t possible, so she received palliative-intent therapy for the next 18 months.
Related: Colorectal Screening: Available but Underused
Initially, the patient responded to the treatment but then presented to the emergency department (ED) with a severe headache. A CT scan revealed that the cancer had spread to her brain. However, this time resection was possible, and she recovered well.
Three weeks later the patient was back in the ED with an infection. A new CT scan showed no evidence of abscess (one of the differential diagnoses). A transthoracic echocardiogram showed a right atrial lesion, and further imaging confirmed a lesion in the right atrium. “Unexpectedly,” her clinicians reported, the lesion originated from the distal inferior vena cava (IVC): She had shown no signs of symptoms of pulmonary embolus or occlusion of the IVC.
Tumor thrombus is rarely reported with colorectal cancer cases, so the patient’s clinicians at first thought the mass in the IVC was bland thrombus, managed with anticoagulation alone. The clinicians felt that the assumption was reasonable, given the link between malignancy and venous thromboembolism; also because the patient had an indwelling central venous catheter. Contrast-enhanced CT scan and contrast-enhanced ultrasound, however, supported the diagnosis of tumor thrombus.
Due to the rarity of tumor thrombus in colorectal cancer, there are no guidelines for diagnosis and management, the clinicians say. In the patient’s case, consultation with cardiologists, radiologists, and gastrointestinal specialists at the cancer center resulted in an offer to extract the thrombus, but the risks and the fact that she was asymptomatic led the patient to decline. She was instead restarted on palliative chemotherapy with heparin in case part of the thrombus was indeed bland thrombus.
The patient’s condition deteriorated over the next 3 months. She and her team agreed that supportive care at home was best. The patient still had no symptoms from the tumor thrombus when she died.
Related: Cancer Prevention and Gastrointestinal Risk
Autopsy supported the suspicion that the original lesion was partly tumor thrombus and partly bland thrombus, reduced by anticoagulation. But autopsy results revealed no embolization of tumor thrombus or bland thrombus into the pulmonary arteries, although there were extensive metastases in the brain, lung, liver, adrenals, and ovaries. Ultimately, the patient’s death was attributed not to the tumor thrombus that extended into the right atrium but to multiorgan failure due to cancer--validating the decisions to not choose surgery for the thrombus.
Source:
Meyers D, Nixon NA, Franko A, Ng D, Tam VC. BMJ Case Rep. 2017;2017:pii:bcr2016218107.
doi: 10.1136/bcr-2016-218107.
A 46-year-old woman went to her family doctor after 3 months of abdominal bloating, fatigue, nausea, vomiting, anorexia, and weight loss. Ultrasound imaging revealed hepatic lesions and a mass in the colon; she was diagnosed with colon cancer. The cancer had metastasized to an extent that complete resection wasn’t possible, so she received palliative-intent therapy for the next 18 months.
Related: Colorectal Screening: Available but Underused
Initially, the patient responded to the treatment but then presented to the emergency department (ED) with a severe headache. A CT scan revealed that the cancer had spread to her brain. However, this time resection was possible, and she recovered well.
Three weeks later the patient was back in the ED with an infection. A new CT scan showed no evidence of abscess (one of the differential diagnoses). A transthoracic echocardiogram showed a right atrial lesion, and further imaging confirmed a lesion in the right atrium. “Unexpectedly,” her clinicians reported, the lesion originated from the distal inferior vena cava (IVC): She had shown no signs of symptoms of pulmonary embolus or occlusion of the IVC.
Tumor thrombus is rarely reported with colorectal cancer cases, so the patient’s clinicians at first thought the mass in the IVC was bland thrombus, managed with anticoagulation alone. The clinicians felt that the assumption was reasonable, given the link between malignancy and venous thromboembolism; also because the patient had an indwelling central venous catheter. Contrast-enhanced CT scan and contrast-enhanced ultrasound, however, supported the diagnosis of tumor thrombus.
Due to the rarity of tumor thrombus in colorectal cancer, there are no guidelines for diagnosis and management, the clinicians say. In the patient’s case, consultation with cardiologists, radiologists, and gastrointestinal specialists at the cancer center resulted in an offer to extract the thrombus, but the risks and the fact that she was asymptomatic led the patient to decline. She was instead restarted on palliative chemotherapy with heparin in case part of the thrombus was indeed bland thrombus.
The patient’s condition deteriorated over the next 3 months. She and her team agreed that supportive care at home was best. The patient still had no symptoms from the tumor thrombus when she died.
Related: Cancer Prevention and Gastrointestinal Risk
Autopsy supported the suspicion that the original lesion was partly tumor thrombus and partly bland thrombus, reduced by anticoagulation. But autopsy results revealed no embolization of tumor thrombus or bland thrombus into the pulmonary arteries, although there were extensive metastases in the brain, lung, liver, adrenals, and ovaries. Ultimately, the patient’s death was attributed not to the tumor thrombus that extended into the right atrium but to multiorgan failure due to cancer--validating the decisions to not choose surgery for the thrombus.
Source:
Meyers D, Nixon NA, Franko A, Ng D, Tam VC. BMJ Case Rep. 2017;2017:pii:bcr2016218107.
doi: 10.1136/bcr-2016-218107.
Prophylactic HIV Pill Also May Help Prevent Some STIs
Pre-exposure prophylaxis ( PrEP)—just 1 pill every day—can reduce the risk HIV infection by > 90%. A recent study shows that > 40% of chlamydia infections and 42% of gonorrhea infections also could be prevented over the next decade if 40% of homosexual and bisexual men took PrEP for HIV and were tested and treated every 6 months.
The CDC estimates that nearly 500,000 men are at “substantial risk” for HIV infection and could benefit from PrEP. But recent evidence suggests that some men may use condoms less when they are taking PrEP. According to researchers from the CDC and The Rollins School of Public Health at Emory University, PrEP prevented some STIs even with a 40% reduction in condom use.
The CDC recommends testing patients who use PrEP for bacterial STIs at least once every 6 months even if they don’t have symptoms. The study found that increasing STI testing from twice a year to 4 times a year would not dramatically affect the prevention of chlamydia or gonorrhea.
PrEP’s effectiveness in preventing HIV is well documented, the CDC says. The new study shows the “potential impact” that following the CDC’s clinical guidelines for PrEP can have on preventing bacterial STIs as well. But about one third of primary health care providers had not heard of PrEP as recently as 2015, the CDC says. To address that need, the CDC has been leading education efforts targeting providers, offering the guidelines, step-by-step PrEP checklists, and interview guides, along with a hotline to answer providers’ questions about when and how to offer PrEP.
Pre-exposure prophylaxis ( PrEP)—just 1 pill every day—can reduce the risk HIV infection by > 90%. A recent study shows that > 40% of chlamydia infections and 42% of gonorrhea infections also could be prevented over the next decade if 40% of homosexual and bisexual men took PrEP for HIV and were tested and treated every 6 months.
The CDC estimates that nearly 500,000 men are at “substantial risk” for HIV infection and could benefit from PrEP. But recent evidence suggests that some men may use condoms less when they are taking PrEP. According to researchers from the CDC and The Rollins School of Public Health at Emory University, PrEP prevented some STIs even with a 40% reduction in condom use.
The CDC recommends testing patients who use PrEP for bacterial STIs at least once every 6 months even if they don’t have symptoms. The study found that increasing STI testing from twice a year to 4 times a year would not dramatically affect the prevention of chlamydia or gonorrhea.
PrEP’s effectiveness in preventing HIV is well documented, the CDC says. The new study shows the “potential impact” that following the CDC’s clinical guidelines for PrEP can have on preventing bacterial STIs as well. But about one third of primary health care providers had not heard of PrEP as recently as 2015, the CDC says. To address that need, the CDC has been leading education efforts targeting providers, offering the guidelines, step-by-step PrEP checklists, and interview guides, along with a hotline to answer providers’ questions about when and how to offer PrEP.
Pre-exposure prophylaxis ( PrEP)—just 1 pill every day—can reduce the risk HIV infection by > 90%. A recent study shows that > 40% of chlamydia infections and 42% of gonorrhea infections also could be prevented over the next decade if 40% of homosexual and bisexual men took PrEP for HIV and were tested and treated every 6 months.
The CDC estimates that nearly 500,000 men are at “substantial risk” for HIV infection and could benefit from PrEP. But recent evidence suggests that some men may use condoms less when they are taking PrEP. According to researchers from the CDC and The Rollins School of Public Health at Emory University, PrEP prevented some STIs even with a 40% reduction in condom use.
The CDC recommends testing patients who use PrEP for bacterial STIs at least once every 6 months even if they don’t have symptoms. The study found that increasing STI testing from twice a year to 4 times a year would not dramatically affect the prevention of chlamydia or gonorrhea.
PrEP’s effectiveness in preventing HIV is well documented, the CDC says. The new study shows the “potential impact” that following the CDC’s clinical guidelines for PrEP can have on preventing bacterial STIs as well. But about one third of primary health care providers had not heard of PrEP as recently as 2015, the CDC says. To address that need, the CDC has been leading education efforts targeting providers, offering the guidelines, step-by-step PrEP checklists, and interview guides, along with a hotline to answer providers’ questions about when and how to offer PrEP.
Combo improves response rates in treatment-naïve SAA
Adding eltrombopag to immunosuppressive therapy (IST) can produce high rates of response in treatment-naïve severe aplastic anemia (SAA), according to research published in NEJM.
In patients who received eltrombopag for 6 months, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 58%.
Researchers noted that these rates are “markedly higher” than response rates observed in historical controls who received IST alone.
The team also said the safety profile of eltrombopag in this study was consistent with the known safety profile of the drug.
“[E]ltrombopag plus standard immunosuppressive therapy appeared to increase the overall response rate and substantially increase the frequency, speed, and robustness of hematologic recovery in patients with SAA compared to historical controls,” said study author Danielle Townsley, MD, of the National Heart, Lung and Blood Institute (NHLBI).
She and her colleagues at NHLBI conducted this research through a Cooperative Research and Development Agreement with Novartis, the company that markets eltrombopag as Promacta/Revolade.
Patients and treatment
This phase 1/2 trial included 92 patients with treatment-naïve SAA. The patients’ median age was 32 (range, 3-82), and 54% of them were male.
At baseline, the patients’ median neutrophil count was 310/mm3 (range, 0-1810), their median reticulocyte count was 19,950/mm3 (range, 1600-60,400), and their median platelet count was 9000/mm3 (range, 0-37,000). Their median thrombopoietin level was 3163 pg/ml (range, 1806-4955).
All patients received horse antithymocyte globulin on days 1 to 4 and cyclosporine from day 1 to 6 months. The patients also received eltrombopag at an age-dependent dose.
They received eltrombopag at 150 mg daily if they were 12 years or older, 75 mg daily if they were 6 to 11, and 2.5 mg/kg/day if they were 2 to 5 years of age.
Patients were also split into 3 cohorts according to treatment duration:
- Cohort 1 received eltrombopag from day 14 to the 6-month mark.
- Cohort 2 received eltrombopag from day 14 to the 3-month mark.
- Cohort 3 received eltrombopag from day 1 to 6 months.
Response
The study’s primary efficacy endpoint was hematologic CR at 6 months. CR was defined as an absolute neutrophil count of at least 1000/mm3, a hemoglobin level of at least 10 g/dL, and a platelet count of at least 100,000/mm3.
Secondary endpoints included partial response (PR) and ORR, among other endpoints. ORR was the rate of CR plus PR. Patients had a PR if they had blood counts that no longer met the criteria for SAA but they did not meet criteria for CR.
For all cohorts, at 6 months, the ORR was 87%, and the CR rate was 39%.
In cohort 1, the ORR was 80%, and the CR rate was 33%.
In cohort 2, the ORR was 87%, and the CR rate was 26%.
In cohort 3, the ORR was 94%, and the CR rate was 58%.
The researchers noted that ORRs were higher across all cohorts than the ORR observed in a historical cohort (66%). The cohort consisted of 102 patients who had received standard IST while serving as controls in 1 of 2 recent NHLBI clinical trials.
Relapse
Thirty-two percent of responding patients (25/78) relapsed after 6 months.
After the study protocol was amended to allow the continuation of low-dose cyclosporine from 6 months to 2 years, the frequency of relapse decreased.
Fourteen percent of responders receiving low-dose cyclosporine beyond 6 months relapsed (6/43), compared to 54% of patients who stopped cyclosporine at 6 months (19/35).
Restarting full-dose cyclosporine reversed relapse and increased blood counts in 13 of 25 patients. Adding eltrombopag reversed relapse in an additional 10 patients.
Survival
The 2-year overall survival rate was 97% for the entire study population and 99% when data were censored for transplant.
Twelve patients under went transplant after eltrombopag. Six of them had not responded or were still transfusion-dependent, 3 relapsed, and 3 had clonal evolution.
Three patients died—1 while on study and 2 after transplant.
Clonal evolution and PNH
The researchers said the frequency of clonal evolution in this study was similar to that observed in the historical cohort of patients who received standard IST. The rate of clonal evolution at 2 years was 8% in both groups.
In the current study, 7 patients had clonal evolution at 2 years. Five patients had loss of chromosome 7, which was associated with dysplastic bone marrow changes in 3 patients.
One patient with a complex karyotype progressed to acute myeloid leukemia.
Two patients developed hemolytic paroxysmal nocturnal hemoglobinuria (PNH).
Safety
Two severe adverse events (AEs) were attributed to eltrombopag. Both were cutaneous eruptions—a grade 2 and a grade 3 event. Both AEs led to discontinuation of the drug.
Seven patients briefly stopped taking eltrombopag during the first 2 weeks of treatment due to transient elevations in liver enzymes.
AEs not attributed to eltrombopag were neutropenic infections and AEs known to be associated with IST.
The single patient who died on study was a non-responder who died 3 months after starting treatment. The death was due to paraneoplastic encephalopathy, which was attributed to thymoma that predated study entry. 
Adding eltrombopag to immunosuppressive therapy (IST) can produce high rates of response in treatment-naïve severe aplastic anemia (SAA), according to research published in NEJM.
In patients who received eltrombopag for 6 months, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 58%.
Researchers noted that these rates are “markedly higher” than response rates observed in historical controls who received IST alone.
The team also said the safety profile of eltrombopag in this study was consistent with the known safety profile of the drug.
“[E]ltrombopag plus standard immunosuppressive therapy appeared to increase the overall response rate and substantially increase the frequency, speed, and robustness of hematologic recovery in patients with SAA compared to historical controls,” said study author Danielle Townsley, MD, of the National Heart, Lung and Blood Institute (NHLBI).
She and her colleagues at NHLBI conducted this research through a Cooperative Research and Development Agreement with Novartis, the company that markets eltrombopag as Promacta/Revolade.
Patients and treatment
This phase 1/2 trial included 92 patients with treatment-naïve SAA. The patients’ median age was 32 (range, 3-82), and 54% of them were male.
At baseline, the patients’ median neutrophil count was 310/mm3 (range, 0-1810), their median reticulocyte count was 19,950/mm3 (range, 1600-60,400), and their median platelet count was 9000/mm3 (range, 0-37,000). Their median thrombopoietin level was 3163 pg/ml (range, 1806-4955).
All patients received horse antithymocyte globulin on days 1 to 4 and cyclosporine from day 1 to 6 months. The patients also received eltrombopag at an age-dependent dose.
They received eltrombopag at 150 mg daily if they were 12 years or older, 75 mg daily if they were 6 to 11, and 2.5 mg/kg/day if they were 2 to 5 years of age.
Patients were also split into 3 cohorts according to treatment duration:
- Cohort 1 received eltrombopag from day 14 to the 6-month mark.
- Cohort 2 received eltrombopag from day 14 to the 3-month mark.
- Cohort 3 received eltrombopag from day 1 to 6 months.
Response
The study’s primary efficacy endpoint was hematologic CR at 6 months. CR was defined as an absolute neutrophil count of at least 1000/mm3, a hemoglobin level of at least 10 g/dL, and a platelet count of at least 100,000/mm3.
Secondary endpoints included partial response (PR) and ORR, among other endpoints. ORR was the rate of CR plus PR. Patients had a PR if they had blood counts that no longer met the criteria for SAA but they did not meet criteria for CR.
For all cohorts, at 6 months, the ORR was 87%, and the CR rate was 39%.
In cohort 1, the ORR was 80%, and the CR rate was 33%.
In cohort 2, the ORR was 87%, and the CR rate was 26%.
In cohort 3, the ORR was 94%, and the CR rate was 58%.
The researchers noted that ORRs were higher across all cohorts than the ORR observed in a historical cohort (66%). The cohort consisted of 102 patients who had received standard IST while serving as controls in 1 of 2 recent NHLBI clinical trials.
Relapse
Thirty-two percent of responding patients (25/78) relapsed after 6 months.
After the study protocol was amended to allow the continuation of low-dose cyclosporine from 6 months to 2 years, the frequency of relapse decreased.
Fourteen percent of responders receiving low-dose cyclosporine beyond 6 months relapsed (6/43), compared to 54% of patients who stopped cyclosporine at 6 months (19/35).
Restarting full-dose cyclosporine reversed relapse and increased blood counts in 13 of 25 patients. Adding eltrombopag reversed relapse in an additional 10 patients.
Survival
The 2-year overall survival rate was 97% for the entire study population and 99% when data were censored for transplant.
Twelve patients under went transplant after eltrombopag. Six of them had not responded or were still transfusion-dependent, 3 relapsed, and 3 had clonal evolution.
Three patients died—1 while on study and 2 after transplant.
Clonal evolution and PNH
The researchers said the frequency of clonal evolution in this study was similar to that observed in the historical cohort of patients who received standard IST. The rate of clonal evolution at 2 years was 8% in both groups.
In the current study, 7 patients had clonal evolution at 2 years. Five patients had loss of chromosome 7, which was associated with dysplastic bone marrow changes in 3 patients.
One patient with a complex karyotype progressed to acute myeloid leukemia.
Two patients developed hemolytic paroxysmal nocturnal hemoglobinuria (PNH).
Safety
Two severe adverse events (AEs) were attributed to eltrombopag. Both were cutaneous eruptions—a grade 2 and a grade 3 event. Both AEs led to discontinuation of the drug.
Seven patients briefly stopped taking eltrombopag during the first 2 weeks of treatment due to transient elevations in liver enzymes.
AEs not attributed to eltrombopag were neutropenic infections and AEs known to be associated with IST.
The single patient who died on study was a non-responder who died 3 months after starting treatment. The death was due to paraneoplastic encephalopathy, which was attributed to thymoma that predated study entry.
Adding eltrombopag to immunosuppressive therapy (IST) can produce high rates of response in treatment-naïve severe aplastic anemia (SAA), according to research published in NEJM.
In patients who received eltrombopag for 6 months, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 58%.
Researchers noted that these rates are “markedly higher” than response rates observed in historical controls who received IST alone.
The team also said the safety profile of eltrombopag in this study was consistent with the known safety profile of the drug.
“[E]ltrombopag plus standard immunosuppressive therapy appeared to increase the overall response rate and substantially increase the frequency, speed, and robustness of hematologic recovery in patients with SAA compared to historical controls,” said study author Danielle Townsley, MD, of the National Heart, Lung and Blood Institute (NHLBI).
She and her colleagues at NHLBI conducted this research through a Cooperative Research and Development Agreement with Novartis, the company that markets eltrombopag as Promacta/Revolade.
Patients and treatment
This phase 1/2 trial included 92 patients with treatment-naïve SAA. The patients’ median age was 32 (range, 3-82), and 54% of them were male.
At baseline, the patients’ median neutrophil count was 310/mm3 (range, 0-1810), their median reticulocyte count was 19,950/mm3 (range, 1600-60,400), and their median platelet count was 9000/mm3 (range, 0-37,000). Their median thrombopoietin level was 3163 pg/ml (range, 1806-4955).
All patients received horse antithymocyte globulin on days 1 to 4 and cyclosporine from day 1 to 6 months. The patients also received eltrombopag at an age-dependent dose.
They received eltrombopag at 150 mg daily if they were 12 years or older, 75 mg daily if they were 6 to 11, and 2.5 mg/kg/day if they were 2 to 5 years of age.
Patients were also split into 3 cohorts according to treatment duration:
- Cohort 1 received eltrombopag from day 14 to the 6-month mark.
- Cohort 2 received eltrombopag from day 14 to the 3-month mark.
- Cohort 3 received eltrombopag from day 1 to 6 months.
Response
The study’s primary efficacy endpoint was hematologic CR at 6 months. CR was defined as an absolute neutrophil count of at least 1000/mm3, a hemoglobin level of at least 10 g/dL, and a platelet count of at least 100,000/mm3.
Secondary endpoints included partial response (PR) and ORR, among other endpoints. ORR was the rate of CR plus PR. Patients had a PR if they had blood counts that no longer met the criteria for SAA but they did not meet criteria for CR.
For all cohorts, at 6 months, the ORR was 87%, and the CR rate was 39%.
In cohort 1, the ORR was 80%, and the CR rate was 33%.
In cohort 2, the ORR was 87%, and the CR rate was 26%.
In cohort 3, the ORR was 94%, and the CR rate was 58%.
The researchers noted that ORRs were higher across all cohorts than the ORR observed in a historical cohort (66%). The cohort consisted of 102 patients who had received standard IST while serving as controls in 1 of 2 recent NHLBI clinical trials.
Relapse
Thirty-two percent of responding patients (25/78) relapsed after 6 months.
After the study protocol was amended to allow the continuation of low-dose cyclosporine from 6 months to 2 years, the frequency of relapse decreased.
Fourteen percent of responders receiving low-dose cyclosporine beyond 6 months relapsed (6/43), compared to 54% of patients who stopped cyclosporine at 6 months (19/35).
Restarting full-dose cyclosporine reversed relapse and increased blood counts in 13 of 25 patients. Adding eltrombopag reversed relapse in an additional 10 patients.
Survival
The 2-year overall survival rate was 97% for the entire study population and 99% when data were censored for transplant.
Twelve patients under went transplant after eltrombopag. Six of them had not responded or were still transfusion-dependent, 3 relapsed, and 3 had clonal evolution.
Three patients died—1 while on study and 2 after transplant.
Clonal evolution and PNH
The researchers said the frequency of clonal evolution in this study was similar to that observed in the historical cohort of patients who received standard IST. The rate of clonal evolution at 2 years was 8% in both groups.
In the current study, 7 patients had clonal evolution at 2 years. Five patients had loss of chromosome 7, which was associated with dysplastic bone marrow changes in 3 patients.
One patient with a complex karyotype progressed to acute myeloid leukemia.
Two patients developed hemolytic paroxysmal nocturnal hemoglobinuria (PNH).
Safety
Two severe adverse events (AEs) were attributed to eltrombopag. Both were cutaneous eruptions—a grade 2 and a grade 3 event. Both AEs led to discontinuation of the drug.
Seven patients briefly stopped taking eltrombopag during the first 2 weeks of treatment due to transient elevations in liver enzymes.
AEs not attributed to eltrombopag were neutropenic infections and AEs known to be associated with IST.
The single patient who died on study was a non-responder who died 3 months after starting treatment. The death was due to paraneoplastic encephalopathy, which was attributed to thymoma that predated study entry.