Jonathan Silverberg, MD, PHD, MPH
George Washington University School of Medicine and Health Sciences
Washington, DC
A new era of evidence-based practice for atopic dermatitis
Atopic dermatitis (AD) is one of the most common diseases of childhood and still very common in adults worldwide. AD is also a very burdensome disease with considerable patient-burden. Despite the enormous population- and patient- burden, there remain many unmet needs in the management of AD. In addition, many treatments commonly used in AD had scant or mixed evidence regarding their efficacy and safety. For example, topical corticosteroids (TCS) are the workhorse for treatment in AD and most other inflammatory skin diseases. Yet, virtually everything we know about the efficacy of TCS comes from vasoconstriction proxy assays with almost no studies formally studying the efficacy of TCS in AD. Similarly, many therapies used off-label to treat more severe AD, such as phototherapy or allergen immunotherapy have inconsistent evidence to guide their use. Well, things are finally changing and the evidence is coming in at a frenzied pace. Development of multiple novel therapeutics in AD led to renewed interest in studying the efficacy and safety of older therapies as well.
- Phototherapy is an important treatment modality in AD patients who have an inadequate response to topical therapy. Many different modalities and devices were used to treat AD over the years, including narrowband ultraviolet B (NBUVB) and ultraviolet A (UVA)-1. NBUVB is the most commonly used approach in the United States and some other regions of the world. Ben Mordehai et al. published the results of a retrospective cohort study of 390 Israeli patients with moderate-severe AD treated with NBUVB therapy between 2000-2017 with ≥3 years of follow-up. Overall, 55.4% achieved an Investigator’s Global Assessment score of clear or almost clear. Facial involvement, occurrence of adverse effects, fewer treatments, and pretreatment immunoglobulin E levels >4000 IU/ml were associated with poorer clinical response to NBUVB. Median duration of response was 12 months with more relapses in children (<18 years).
- House dust mites (HDM) were previously shown to be triggers of AD via Immunoglobulin E dependent and independent mechanisms. Unfortunately, HDM avoidance is challenging for patients and has not proven to be reliably effective in clinical trials. Previous studies examined different approaches for immunotherapy to HDM with mixed results. Langer et al. published the results of a randomized, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT) or placebo for 18 months in 91 children and adults with AD and positive skin test result and/or Immunoglobulin E to Dermatophagoides pteronyssinus. After 18 months, patients treated with HDM SLIT achieved greater reductions in the SCOring AD (SCORAD) index and were more likely to achieve an Investigator’s Global Assessment score of clear or almost clear compared to placebo. Headache and abdominal pain were the most common adverse events reported by both groups. Efficacy of HDM SLIT in this study was relatively modest. Nevertheless, it appears to be a safe therapy and a reasonable adjunctive therapy in patients with AD whose disease is believed to be triggered by HDM.
- We are fortunate to have multiple non-steroidal topical therapies for atopic dermatitis, including crisaborole ointment, pimecrolimus cream and tacrolimus ointment. A number of questions remain about how these therapies compare with each other and with topical corticosteroids. Some of these questions were answered in two recent studies.
- Thom et al. compared individual data from two phase 3 studies of crisaborole ointment with previously published data for topical pimecrolimus and tacrolimus in patients ≥2 years with mild-to-moderate AD using an approach referred to as unanchored matching-adjusted indirect comparison. By week 6, the odds of achieving Investigator’s Static Global Assessment score of 0/1 was higher for crisaborole ointment vs. pimecrolimus cream and tacrolimus 0.03% ointment.
- Salava et al. followed 152 children age 1-3 years with moderate-severe AD for 36 months. They found no significant differences of topical tacrolimus 0.03% or 0.1% ointment vs. low or mid potency topical corticosteroids on AD severity (as judged by the eczema area and severity index), skin or other infections, and various cytokine levels.
While these data do not replace the need for head-to-head studies, they do provide important context about comparative efficacy and safety of the various topical agents in our toolbox.
References
- Ben Mordehai Y et al. Long-Term Narrowband UV-B Efficacy in Moderate to Severe Atopic Dermatitis. Dermatitis. 2021 (Nov 27).
- Langer SS et al. Efficacy of house dust mite sublingual immunotherapy in patients with atopic dermatitis: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol Pract. 2021 (Nov 9).
- Thom H et al. Matching-Adjusted Indirect Comparison of Crisaborole Ointment 2% vs. Topical Calcineurin Inhibitors in the Treatment of Patients with Mild-to-Moderate Atopic Dermatitis Dermatol Ther (Heidelb). 2021 (Dec 8).
- Salava A et al. Safety of tacrolimus 0.03% and 0.1% ointments in young children with atopic dermatitis - a 36-month follow-up study. Clin Exp Dermatol. 2021 (Nov 19).