Atopic dermatitis (AD), the most common form of eczema, is a chronically relapsing inflammatory skin disease with a complex pathogenesis affecting up to 25% of children in industrialized countries. One-third of cases persist into adulthood, with a prevalence of 2% to 10%.1 In the United States, the prevalence of childhood eczema/AD is 10.7% overall and as high as 18.1% in individual states, according to the National Eczema Association.2 The pathogenesis of AD involves complex interactions between susceptible genes, immunologic factors, skin barrier defects, and neuroendocrine and environmental factors.3
A Challenging Disease
Because its exact cause is unknown, it is a challenging disease for dermatologists to treat and manage. “The cause of eczema/AD is complex and difficult to explain. Patients are often focused on a simple solution, such as eliminating a food from their diet, which is unlikely to improve the situation. No one wants to be told they could be dealing with a skin problem that can be for their whole life,” said Anna L. Bruckner, MD, associate professor of dermatology and pediatrics, University of Colorado School of Medicine,” in an interview with The Dermatologist.
“Most patients are not willing to acknowledge AD as a chronic condition. Proper treatment of AD requires long-term commitment to gentle skin care and use of topical corticosteroids during flares. Some patients benefit from daily use of a topical calcineurin inhibitor or phosphodiesterase inhibitor to prevent flares,” said John C. Browning, MD, MBA, FAAD, FAAP, chief of dermatology, Children’s Hospital of San Antonio.
In addition to dispelling the myths associated with chronic disease, lack of well-defined optimal treatment, and input from various sources (ie, well-meaning relatives, the internet), access to prescription medication is huge barrier, according to Elaine Siegfried, MD, professor of pediatrics and dermatology, Saint Louis University. “Payers have limited formularies and they often deny coverage for a variety of medications for kids who have skin disease. Because eczema is so common, it is among the most common denials that we get,” Dr Siegfried told The Dermatologist.
“The amount of time our office is forced to spend trying to justify the prescriptions we write and gain access to medications for our patients is growing and becoming relatively insurmountable. About 50% of my patients have eczema, but it takes 90% of my time to manage them,” she said.
Advances in Eczema/AD Treatment
Recent FDA approvals of therapies to treat eczema/AD are offering new treatment options for individuals living with skin disease. “After so many years of trying to help patients manage their disease with almost nothing that has labeling for this disease in the pediatric age group, we finally have an expanding pipeline,” noted Dr Siegfried.
In late 2106, the FDA approved crisaborole (Eucrisa) for mild to moderate AD in patients aged 2 years and older. This topical phosphodiesterase-4 (PDE4) inhibitor marked the first drug approved in 15 years for eczema. The approval of crisaborole is “very exciting as it has been studied in patients 2 and up with AD as a daily application. Treatment breaks are not required, as is with topical steroids,” said Dr Browning, who is also an assistant professor at Baylor College of Medicine.
The safety and efficacy of crisaborole were established in 2 identically designed, vehicle-controlled, double-blind, phase 3 studies (AD-301 and AD-302) with a total of 1522 participants (aged 2-79 years) with mild to moderate AD. Overall, the participants receiving crisaborole achieved greater response with clear or almost clear skin at day 29 of treatment (AD-301, 51.7% and AD-302, 48.5%). Crisaborole demonstrated a favorable safety profile and treatment-related adverse events were infrequent and mild to moderate in severity. The most common adverse event was application site pain, including burning, or stinging.4
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In March 2017, the FDA approved dupilumab (Dupixent), the first biologic for the treatment of adults with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not available. Dupilumab is a human monoclonal antibody that is designed specifically to inhibit overactive signaling of 2 key proteins, IL-4 and IL-13, which are believed to be major drivers of the persistent underlying inflammation in AD.5
Dupilumab has been studied in pivotal trials as a monotherapy and with topical corticosteroids. Two identical, randomized, double-blind, placebo-group, phase 3 trials of dupilumab monotherapy (SOLO 1 and SOLO 2) included 1379 participants with inadequately controlled moderate to severe AD. Simpson and colleagues reported that dupilumab met the primary endpoint in both studies—a score of 0 or 1 (clear or almost clear) on the 5-point Investigator’s Global Assessment (IGA). At 16 weeks, in SOLO 1, 38% and 37% of participants, respectively, who received dupilumab 300 mg every other week or weekly achieved clear or almost clear skin; the results were similar in SOLO 2, with 36% of participants in each treatment arm achieving the primary endpoint. The most common adverse events in both studies were exacerbations of AD, injection-site reactions, and nasopharyngitis.6
"This biggest challenge with dupilumab is access because it is very expensive and we are having difficulty accessing it off-label for children,” explained Dr Siegfried. “Although eczema occurs in adults, it is primarily a disease of children and has its onset in infancy. We have less data and higher sensitivity for potential adverse effects associated with off-label medications that we use.”
Regeneron and Sanofi Genzyme, who market dupilumab in the United States, launched Dupixent MyWay, a specialized program that provides support and services to patients during the treatment process, and also helps eligible patients who are uninsured, lack coverage, or who need assistance with out-of-pocket costs. Dr Siegfried noted that children are not able to benefit from the program because it is used off-label in this patient population.
The companies announced in March that dupilumab is being evaluated in a comprehensive development program for AD that includes studies in children with severe AD (aged 6 months to 11 years) and adolescents with moderate to severe AD (aged 12-17 years). In October 2016, the FDA granted dupilumab Breakthrough Therapy designation for both populations.5
References
1. D’Erme AM, Romanelli M, Chiricozzi A. Spotlight on dupilumab in the treatment of atopic dermatitis: design, development, and potential place in therapy. Drug Des Devel Ther. 2017;11:1473-1480.
2. Facts about eczema. National Eczema Association website. https://nationaleczema.org/wp-content/uploads/2016/08/Media-Kit-FINAL-08.11.16.pdf?2b800d. Accessed September 13, 2017.
3. Hon KL, Leung AK, Barankin B. Barrier repair therapy in atopic dermatitis: an overview. Am J Clin Dermatol. 2013;14(5):389-399.
4. Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults: J Am Acad Dermatol. 2016;75(3):494-503.e6.
5. The first biologic approved to treat moderate to severe AD. The Dermatologist. 2017;25(4):42-44.
6. Simpson EL, Beiber T, Guttman-Yassky E, et al; SOLO 1 and SOLO Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348.
7. Eichenfield LF, Friedlander SF, Simpson, EL, Irvine AD. Assessing the new and emerging treatments for atopic dermatitis. Semin Cutan Med Surg. 2016;35(5 suppl): S92-S96.
8. Renert-Yuval Y, Guttman-Yassky E. Systemic therapies in atopic dermatitis: the pipeline. Clin Dermatol. 2017;35(4):387-397.
9. Ruzicka T, Hanifin JM, Furue M, et al; XCIMA Study Group. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017;376(9):826-835.
10. Hanifin JM, Ellis CN, Frieden IJ, et al. OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2016;75(2):297-305.
Atopic dermatitis (AD), the most common form of eczema, is a chronically relapsing inflammatory skin disease with a complex pathogenesis affecting up to 25% of children in industrialized countries. One-third of cases persist into adulthood, with a prevalence of 2% to 10%.1 In the United States, the prevalence of childhood eczema/AD is 10.7% overall and as high as 18.1% in individual states, according to the National Eczema Association.2 The pathogenesis of AD involves complex interactions between susceptible genes, immunologic factors, skin barrier defects, and neuroendocrine and environmental factors.3
A Challenging Disease
Because its exact cause is unknown, it is a challenging disease for dermatologists to treat and manage. “The cause of eczema/AD is complex and difficult to explain. Patients are often focused on a simple solution, such as eliminating a food from their diet, which is unlikely to improve the situation. No one wants to be told they could be dealing with a skin problem that can be for their whole life,” said Anna L. Bruckner, MD, associate professor of dermatology and pediatrics, University of Colorado School of Medicine,” in an interview with The Dermatologist.
“Most patients are not willing to acknowledge AD as a chronic condition. Proper treatment of AD requires long-term commitment to gentle skin care and use of topical corticosteroids during flares. Some patients benefit from daily use of a topical calcineurin inhibitor or phosphodiesterase inhibitor to prevent flares,” said John C. Browning, MD, MBA, FAAD, FAAP, chief of dermatology, Children’s Hospital of San Antonio.
In addition to dispelling the myths associated with chronic disease, lack of well-defined optimal treatment, and input from various sources (ie, well-meaning relatives, the internet), access to prescription medication is huge barrier, according to Elaine Siegfried, MD, professor of pediatrics and dermatology, Saint Louis University. “Payers have limited formularies and they often deny coverage for a variety of medications for kids who have skin disease. Because eczema is so common, it is among the most common denials that we get,” Dr Siegfried told The Dermatologist.
“The amount of time our office is forced to spend trying to justify the prescriptions we write and gain access to medications for our patients is growing and becoming relatively insurmountable. About 50% of my patients have eczema, but it takes 90% of my time to manage them,” she said.
Advances in Eczema/AD Treatment
Recent FDA approvals of therapies to treat eczema/AD are offering new treatment options for individuals living with skin disease. “After so many years of trying to help patients manage their disease with almost nothing that has labeling for this disease in the pediatric age group, we finally have an expanding pipeline,” noted Dr Siegfried.
In late 2106, the FDA approved crisaborole (Eucrisa) for mild to moderate AD in patients aged 2 years and older. This topical phosphodiesterase-4 (PDE4) inhibitor marked the first drug approved in 15 years for eczema. The approval of crisaborole is “very exciting as it has been studied in patients 2 and up with AD as a daily application. Treatment breaks are not required, as is with topical steroids,” said Dr Browning, who is also an assistant professor at Baylor College of Medicine.
The safety and efficacy of crisaborole were established in 2 identically designed, vehicle-controlled, double-blind, phase 3 studies (AD-301 and AD-302) with a total of 1522 participants (aged 2-79 years) with mild to moderate AD. Overall, the participants receiving crisaborole achieved greater response with clear or almost clear skin at day 29 of treatment (AD-301, 51.7% and AD-302, 48.5%). Crisaborole demonstrated a favorable safety profile and treatment-related adverse events were infrequent and mild to moderate in severity. The most common adverse event was application site pain, including burning, or stinging.4
{{pagebreak}}
In March 2017, the FDA approved dupilumab (Dupixent), the first biologic for the treatment of adults with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not available. Dupilumab is a human monoclonal antibody that is designed specifically to inhibit overactive signaling of 2 key proteins, IL-4 and IL-13, which are believed to be major drivers of the persistent underlying inflammation in AD.5
Dupilumab has been studied in pivotal trials as a monotherapy and with topical corticosteroids. Two identical, randomized, double-blind, placebo-group, phase 3 trials of dupilumab monotherapy (SOLO 1 and SOLO 2) included 1379 participants with inadequately controlled moderate to severe AD. Simpson and colleagues reported that dupilumab met the primary endpoint in both studies—a score of 0 or 1 (clear or almost clear) on the 5-point Investigator’s Global Assessment (IGA). At 16 weeks, in SOLO 1, 38% and 37% of participants, respectively, who received dupilumab 300 mg every other week or weekly achieved clear or almost clear skin; the results were similar in SOLO 2, with 36% of participants in each treatment arm achieving the primary endpoint. The most common adverse events in both studies were exacerbations of AD, injection-site reactions, and nasopharyngitis.6
"This biggest challenge with dupilumab is access because it is very expensive and we are having difficulty accessing it off-label for children,” explained Dr Siegfried. “Although eczema occurs in adults, it is primarily a disease of children and has its onset in infancy. We have less data and higher sensitivity for potential adverse effects associated with off-label medications that we use.”
Regeneron and Sanofi Genzyme, who market dupilumab in the United States, launched Dupixent MyWay, a specialized program that provides support and services to patients during the treatment process, and also helps eligible patients who are uninsured, lack coverage, or who need assistance with out-of-pocket costs. Dr Siegfried noted that children are not able to benefit from the program because it is used off-label in this patient population.
The companies announced in March that dupilumab is being evaluated in a comprehensive development program for AD that includes studies in children with severe AD (aged 6 months to 11 years) and adolescents with moderate to severe AD (aged 12-17 years). In October 2016, the FDA granted dupilumab Breakthrough Therapy designation for both populations.5
References
1. D’Erme AM, Romanelli M, Chiricozzi A. Spotlight on dupilumab in the treatment of atopic dermatitis: design, development, and potential place in therapy. Drug Des Devel Ther. 2017;11:1473-1480.
2. Facts about eczema. National Eczema Association website. https://nationaleczema.org/wp-content/uploads/2016/08/Media-Kit-FINAL-08.11.16.pdf?2b800d. Accessed September 13, 2017.
3. Hon KL, Leung AK, Barankin B. Barrier repair therapy in atopic dermatitis: an overview. Am J Clin Dermatol. 2013;14(5):389-399.
4. Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults: J Am Acad Dermatol. 2016;75(3):494-503.e6.
5. The first biologic approved to treat moderate to severe AD. The Dermatologist. 2017;25(4):42-44.
6. Simpson EL, Beiber T, Guttman-Yassky E, et al; SOLO 1 and SOLO Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348.
7. Eichenfield LF, Friedlander SF, Simpson, EL, Irvine AD. Assessing the new and emerging treatments for atopic dermatitis. Semin Cutan Med Surg. 2016;35(5 suppl): S92-S96.
8. Renert-Yuval Y, Guttman-Yassky E. Systemic therapies in atopic dermatitis: the pipeline. Clin Dermatol. 2017;35(4):387-397.
9. Ruzicka T, Hanifin JM, Furue M, et al; XCIMA Study Group. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017;376(9):826-835.
10. Hanifin JM, Ellis CN, Frieden IJ, et al. OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2016;75(2):297-305.
Atopic dermatitis (AD), the most common form of eczema, is a chronically relapsing inflammatory skin disease with a complex pathogenesis affecting up to 25% of children in industrialized countries. One-third of cases persist into adulthood, with a prevalence of 2% to 10%.1 In the United States, the prevalence of childhood eczema/AD is 10.7% overall and as high as 18.1% in individual states, according to the National Eczema Association.2 The pathogenesis of AD involves complex interactions between susceptible genes, immunologic factors, skin barrier defects, and neuroendocrine and environmental factors.3
A Challenging Disease
Because its exact cause is unknown, it is a challenging disease for dermatologists to treat and manage. “The cause of eczema/AD is complex and difficult to explain. Patients are often focused on a simple solution, such as eliminating a food from their diet, which is unlikely to improve the situation. No one wants to be told they could be dealing with a skin problem that can be for their whole life,” said Anna L. Bruckner, MD, associate professor of dermatology and pediatrics, University of Colorado School of Medicine,” in an interview with The Dermatologist.
“Most patients are not willing to acknowledge AD as a chronic condition. Proper treatment of AD requires long-term commitment to gentle skin care and use of topical corticosteroids during flares. Some patients benefit from daily use of a topical calcineurin inhibitor or phosphodiesterase inhibitor to prevent flares,” said John C. Browning, MD, MBA, FAAD, FAAP, chief of dermatology, Children’s Hospital of San Antonio.
In addition to dispelling the myths associated with chronic disease, lack of well-defined optimal treatment, and input from various sources (ie, well-meaning relatives, the internet), access to prescription medication is huge barrier, according to Elaine Siegfried, MD, professor of pediatrics and dermatology, Saint Louis University. “Payers have limited formularies and they often deny coverage for a variety of medications for kids who have skin disease. Because eczema is so common, it is among the most common denials that we get,” Dr Siegfried told The Dermatologist.
“The amount of time our office is forced to spend trying to justify the prescriptions we write and gain access to medications for our patients is growing and becoming relatively insurmountable. About 50% of my patients have eczema, but it takes 90% of my time to manage them,” she said.
Advances in Eczema/AD Treatment
Recent FDA approvals of therapies to treat eczema/AD are offering new treatment options for individuals living with skin disease. “After so many years of trying to help patients manage their disease with almost nothing that has labeling for this disease in the pediatric age group, we finally have an expanding pipeline,” noted Dr Siegfried.
In late 2106, the FDA approved crisaborole (Eucrisa) for mild to moderate AD in patients aged 2 years and older. This topical phosphodiesterase-4 (PDE4) inhibitor marked the first drug approved in 15 years for eczema. The approval of crisaborole is “very exciting as it has been studied in patients 2 and up with AD as a daily application. Treatment breaks are not required, as is with topical steroids,” said Dr Browning, who is also an assistant professor at Baylor College of Medicine.
The safety and efficacy of crisaborole were established in 2 identically designed, vehicle-controlled, double-blind, phase 3 studies (AD-301 and AD-302) with a total of 1522 participants (aged 2-79 years) with mild to moderate AD. Overall, the participants receiving crisaborole achieved greater response with clear or almost clear skin at day 29 of treatment (AD-301, 51.7% and AD-302, 48.5%). Crisaborole demonstrated a favorable safety profile and treatment-related adverse events were infrequent and mild to moderate in severity. The most common adverse event was application site pain, including burning, or stinging.4
{{pagebreak}}
In March 2017, the FDA approved dupilumab (Dupixent), the first biologic for the treatment of adults with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not available. Dupilumab is a human monoclonal antibody that is designed specifically to inhibit overactive signaling of 2 key proteins, IL-4 and IL-13, which are believed to be major drivers of the persistent underlying inflammation in AD.5
Dupilumab has been studied in pivotal trials as a monotherapy and with topical corticosteroids. Two identical, randomized, double-blind, placebo-group, phase 3 trials of dupilumab monotherapy (SOLO 1 and SOLO 2) included 1379 participants with inadequately controlled moderate to severe AD. Simpson and colleagues reported that dupilumab met the primary endpoint in both studies—a score of 0 or 1 (clear or almost clear) on the 5-point Investigator’s Global Assessment (IGA). At 16 weeks, in SOLO 1, 38% and 37% of participants, respectively, who received dupilumab 300 mg every other week or weekly achieved clear or almost clear skin; the results were similar in SOLO 2, with 36% of participants in each treatment arm achieving the primary endpoint. The most common adverse events in both studies were exacerbations of AD, injection-site reactions, and nasopharyngitis.6
"This biggest challenge with dupilumab is access because it is very expensive and we are having difficulty accessing it off-label for children,” explained Dr Siegfried. “Although eczema occurs in adults, it is primarily a disease of children and has its onset in infancy. We have less data and higher sensitivity for potential adverse effects associated with off-label medications that we use.”
Regeneron and Sanofi Genzyme, who market dupilumab in the United States, launched Dupixent MyWay, a specialized program that provides support and services to patients during the treatment process, and also helps eligible patients who are uninsured, lack coverage, or who need assistance with out-of-pocket costs. Dr Siegfried noted that children are not able to benefit from the program because it is used off-label in this patient population.
The companies announced in March that dupilumab is being evaluated in a comprehensive development program for AD that includes studies in children with severe AD (aged 6 months to 11 years) and adolescents with moderate to severe AD (aged 12-17 years). In October 2016, the FDA granted dupilumab Breakthrough Therapy designation for both populations.5
References
1. D’Erme AM, Romanelli M, Chiricozzi A. Spotlight on dupilumab in the treatment of atopic dermatitis: design, development, and potential place in therapy. Drug Des Devel Ther. 2017;11:1473-1480.
2. Facts about eczema. National Eczema Association website. https://nationaleczema.org/wp-content/uploads/2016/08/Media-Kit-FINAL-08.11.16.pdf?2b800d. Accessed September 13, 2017.
3. Hon KL, Leung AK, Barankin B. Barrier repair therapy in atopic dermatitis: an overview. Am J Clin Dermatol. 2013;14(5):389-399.
4. Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults: J Am Acad Dermatol. 2016;75(3):494-503.e6.
5. The first biologic approved to treat moderate to severe AD. The Dermatologist. 2017;25(4):42-44.
6. Simpson EL, Beiber T, Guttman-Yassky E, et al; SOLO 1 and SOLO Investigators. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348.
7. Eichenfield LF, Friedlander SF, Simpson, EL, Irvine AD. Assessing the new and emerging treatments for atopic dermatitis. Semin Cutan Med Surg. 2016;35(5 suppl): S92-S96.
8. Renert-Yuval Y, Guttman-Yassky E. Systemic therapies in atopic dermatitis: the pipeline. Clin Dermatol. 2017;35(4):387-397.
9. Ruzicka T, Hanifin JM, Furue M, et al; XCIMA Study Group. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017;376(9):826-835.
10. Hanifin JM, Ellis CN, Frieden IJ, et al. OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2016;75(2):297-305.
