“We know that AD is associated with varying severity, flares of disease and long-term persistence as well as periods of quiescence, yet its long-term course isn’t often incorporated into guidelines or clinical studies,” Chovatiya, assistant professor in the department of dermatology at Northwestern University, Chicago, stated during the Revolutionizing Atopic Dermatitis virtual symposium. Understanding the long-term course of AD could aid in understanding our patients and the prognosis.
AD is a common belief that is prevalent in childhood and lasts for a few years before it comes to an end. “I believe we all know that this is not the case,” he said. “This was largely based on anecdotal clinical experiences and large cross-sectional studies which did not consider the heterogeneity in AD.
Results from a large-scale, prospective study of 7,157 children in the Pediatric Eczema Elective Registry (PEER) indicates that AD commonly persists beyond adulthood. PEER was a phase IV postmarketing safety study of children aged 12-17 with moderate or severe AD who were exposed to topical pimecrolimus, and who were surveyed every 6 months (JAMA Dermatol. 2014;150:593-600). The researchers found that more persistent illness was associated with self-reported disease activity, many environmental exposures, White race, history of AD and a household income of less than $50,000. Half of those who were 20 and older reported at least a 6-month period without symptoms or taking medication. Chovatiya said that the most important takeaway was that more than 80% of people aged 20 and above had active AD. This means that the rate of persistence was higher than initially thought. “If you look at the literature prior this study, many were retrospective analyses, and persistence was estimated to be between 40 and 60% range.”
International prospective studies have provided a more accurate estimate of the persistence. For example, the German Multicenter Allergy Study followed 1,314 patients from birth until age 7 (J Allergy Clin Immunol. 2004;113:925-31). 22% of these people had AD within the first two years of their lives. 43% of them were in remission at the age of 3, 38% had intermittent AD, and 19% experienced symptoms throughout the year. Chovatiya noted that studies of other birth cohorts around the globe suggested that AD persists for a long time. Rates range from single digits into the teens.
Researchers conducted an exhaustive review of 45 studies that included 110,651 subjects from 15 different countries and covered 434,992 years of patient care (J Am Acad Dermatol). This was to compare the different estimates of AD persistence. 2016;75:681-7.e11). They found that 80% of childhood AD had at least one period of disease clearance by age 8. Chovatiya stated that less than 5% of childhood AD remained persistent 20 years after diagnosis. “However, interestingly, increased persistence was associated with later onset AD, more years of persistence, and more patient/caregiver-assessed disease.” He said that all studies on AD persistence have their limitations that include non-uniform data collection methods, differing cohorts, different methods to diagnose AD and severity scales that differ and the fact that many doctors do not evaluate flares or recurrences following the initial period of clearing. He suggested that this could result in an under or overestimation in the long-term persistence.
There are distinct predictors of persistence in childhood AD that can help determine AD pathologies. In several studies, chronic disease was associated to higher baseline severity, earlier-onset AD and personal history of AD.
“When it comes to evaluating the longitudinal course of AD in clinical practice, taking into account fluctuation, persistence, and improvement over time may actually improve our clinical decision-making and help us set realistic expectations for our patients,” Chovatiya said. “I think that AD classification could learn the lessons of asthma. If we think about what allergy experts perceive asthma, it’s usually classified as mild persistent, intermittent moderate persistent, or severe persistent. Patients with intermittent disease receive treatment, while those with persistent disease get proactive treatment. In the same way, AD could be classified as mild intermittent moderate persistent, mild to severe intermittent, and moderate to severe persistent.”
He concluded his presentation by suggesting that the varying course of AD be better captured in clinical trials. “Current controlled, randomized trials employ validated measures of AD symptoms and signs as inclusion criteria and indicators of efficacy,” he said. “Static tests can misinterpret treatments effects, and predefined dates can be untrue in the context of disease subsets. He suggests studies that focus on the overall measures of long-term disease control, like the the number of days without itch, weeks with clear skin and flares that occur. “Long-term control assessment in RCTs should include symptoms, signs health-related quality of living, and a patient global domain over time to better understand how AD is doing in the long run,” he said.
Chovatiya has disclosed that he’s a consultant to and a speaker for and/or a member of the advisory board of AbbVie, Arcutis, Arena, Incyte, Pfizer, Regeneron and Sanofi Genzyme.
This article first appeared on MDedge.com, part of the Medscape Professional Network.
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