Collaborative seeks protocols, data for pediatric dermatoses therapies

January 1, 2011

Evidence-based treatment options for moderate-to-severe pediatric atopic dermatitis and psoriasis are severely limited, according to specialists in the field, leading to the creation of a national collaborative by several pediatric dermatologists.

National report - Evidence-based treatment options for moderate-to-severe pediatric atopic dermatitis and psoriasis are severely limited, according to specialists in the field, leading to the creation of a national collaborative by several pediatric dermatologists.

The collaborative aims to gather information on pediatric patients who are receiving systemic treatments at several medical centers. The group specifically is targeting inflammatory conditions, beginning with atopic dermatitis, as this area has the greatest unmet need in terms of research data, says Wynnis Tom, M.D., assistant clinical professor in the departments of pediatrics and medicine (dermatology) at the University of California, San Diego, and Rady Children’s Hospital-San Diego.

At present, there are drugs or biologic agents with a pediatric indications for these diseases that have been approved by the Food and Drug Administration.

Wynnis Tom, M.D.

“This makes it much more difficult to obtain treatments for children with severe disease, as insurance plans often will not approve treatments such as biologic agents, citing the lack of pediatric data and approval,” says Dr. Tom, who is a member of the collaborative.

Collaborative hope
The collaborative, initiated by a group of pediatric dermatologists, is called the Pediatric Dermatology Research Alliance (PEDRA). Among its founding members are Amy Paller, M.D., at Northwestern University Feinberg School of Medicine, and Lawrence Eichenfield, M.D., at the University of California, San Diego, and Rady Children’s Hospital-San Diego. Other members include Ilona Frieden, M.D., Kelly Cordoro, M.D., and Jeff Sugarman, M.D., at the University of California San Francisco Medical Center; Elaine Siegfried, M.D., at Saint Louis University Health Sciences Center, St. Louis; Lisa Beck, M.D., at University of Rochester Medical Center, Rochester, N.Y.; and Dr. Tom.

The inflammatory skin group collaborative first started “meeting” together through conference calls in 2009 in an effort to organize information. Through subsequent discussions, the group decided to form a global research organization.

“We came up with the name in July 2010 at the Society for Pediatric Dermatology meeting in our annual research afternoon that Jeff Sugarman chairs and I co-chair),” Dr. Paller says. “We see PEDRA as an umbrella organization for all clinical research activity in pediatric dermatology.

Amy Paller, M.D.

“The hemangioma investigator's group is well organized - and as we move forward will hopefully be under the same umbrella. Similarly, the inflammatory skin disease group (PEDRA-ISD) is a subset. There is also an Epidermolysis Bullosa research group under the umbrella of PEDRA (PEDRA-EB) - and hopefully more to come.”

Dr. Paller points out, “PEDRA is modeled after the hugely successful and well-organized CARRA (Childhood Arthritis and Rheumatology Research Alliance), which has enabled a broad network of pediatric rheumatologists to work collaboratively in studying patients in a systematic manner with federal grant support.”

The collaborative has several goals: pulling together to give more robust data, generating more safety and efficacy data, and developing more uniform protocols of dosing and monitoring.

“By using similar methods in treating and following the kids, we get to make comparisons to see who tends to respond better, to which therapy, and for how much longer. Therefore, we can hopefully determine how to use these medicines in as safe a manner as possible with less risk for the kids, and get a better sense of efficacy across drugs,” Dr. Tom says.

Research dearth
The lack of data for pediatric dermatitis treatment options has a significant impact for those children whose skin disease detrimentally impacts their lives, the physicians say.

“These are the kids who have failed not just intensive topical and adjunctive therapies, but they have such chronic, severe disease that it is a tremendous burden on their quality of life, sleep and ability to focus in school. In the case of eczema, they often suffer from repeated infections,” Dr. Tom says. These children have the degree of skin disease where phototherapy or systemic treatments are in order.

“However, a lot of times for young kids, trying to use the light box is not very practical or easy, and it is not very effective for the severely flaring atopic patient,” she adds.

Dr. Tom says when treating pediatric atopic dermatitis, she mostly uses systemic immunosupppressives, including azathioprine, mycophenolate, cyclosporine and methotrexate.

“Though used low-dose, we do worry of potential long-term side effects with these drugs,” she says. “My hope would be that we would have more targeted therapies for atopic dermatitis. But these just aren’t available at the moment.” Dr. Tom says some physicians are using biologic agents from other conditions, such as rituximab, for atopic dermatitis but the research is still very early. Pediatric trials are greatly needed, she says.

“Despite the great number of trials in adults, particularly in psoriasis, many fewer have been conducted in children,” Dr. Tom says. “It is more difficult to study kids and have studies sponsored by pharmaceutical companies for this age group.” Also, many of the older medicines, such as cyclosporine and azathioprine, are off patent and available in generic forms.

“Therefore, we can’t really get companies to fund research studies for these drugs. So, it is hard to have large-scale trials in this area,” Dr. Tom says.

Protocols
PEDRA’s first project is to create collaborative protocols for systemic therapy of atopic dermatitis. “These protocols have been established, including outcomes measures that will be reliable and reportable across centers,” Dr. Eichenfield says. “Dr. Wynnis Tom has established electronic methods to generate both ‘EASI and SCORAD’ scores of atopic dermatitis from patient visits (the two standardized eczema scores used in studies), and is working on methods of using electronic medical records to input study data.”

Lawrence Eichenfield, M.D.

Dr. Tom adds, “We have developed drug administration and monitoring protocols for the four main systemic agents used for pediatric atopic dermatitis and are in the process of obtaining IRB approval to start data collection.”

These protocols for the use of cyclosporine, azathioprine, mycophenylate mofetil and methotrexate - including appropriate baseline and follow-up laboratory screening, and standardized dosing - should allow safer use of these medications and tremendous insight into their relative safety and efficacy, Dr. Eichenfield says.

Future goals
“The power of collaborative research is tremendous, especially with rarer conditions in pediatric dermatology. The plan is for PEDRA to begin with a set of studies on inflammatory skin disease (PEDRA-ISD), with severe atopic dermatitis initially, and expanding (quickly) to psoriasis,” Dr. Eichenfield says. “It is also expected that PEDRA will expand to many more pediatric dermatology centers, increasing the ability to research and discover best therapies, as well as allow us to assess biomarkers, disease genetics, disease comorbidities, and for the study of new agents developed through translational medicine initiatives.”

“Ultimately, we would all love to see newer drugs with pediatric indications and more pediatric trials for this group of children who are the most severely affected,” Dr. Tom says.

The collaborative may seek to do more multicenter studies in pediatric psoriasis and other conditions, and will look to get funding through foundations or the National Institutes of Health to get the studies up and running. One future goal is to expand to form a much bigger research collaborative.

“Members of the initial group have worked collaboratively in studies related to inflammatory skin disease for many years, and our early efforts, including collating our collaborative record of past studies and published manuscripts, will form the basis for expansion to a much larger network of collaborators within PEDRA and the inflammatory skin disease subset,” Dr. Paller says.

Disclosures: Drs. Eichenfield, Paller and Tom report no relevant financial interests.