Phototherapy

Ultraviolet (UV) light, either UVB or UVA, in combination with a photosensitizing agent is used for the treatment of AD much in the way UV light is used for treatment of psoriasis. Phototherapy is often used when there is widespread skin involvement but systemic therapy is either not needed or not desired. Patients are treated in the office 2 to 3 times weekly, and benefits begin to be seen after several weeks of therapy. The inconvenience of treatment makes this impractical in many cases.

Systemic Treatments

When the extent and severity of AD precludes topical treatment or phototherapy, or when these modes of treatment have been tried and are not adequately effective, systemic agents may be considered. Systemic steroids, azathioprine, methotrexate, and cyclosporine are the most commonly prescribed agents. Use of these therapies is complicated by the number and severity of adverse events and the need for careful monitoring of patients. Systemic steroids are particularly troublesome given the plethora of medically significant adverse events and the potential for rebound flares upon discontinuation. The role of antihistamines in the treatment of AD deserves special mention; nonsedating antihistamines are not effective for AD, and the beneficial effects of sedating antihistamines are achieved through decreased scratching during sleep.

Biologic Agents

We are currently at the advent of a new era, as the use of biologics such as dupilumab has transformed the management of AD. Dupilumab is a biologic drug that was approved by the US Food and Drug Administration in March of 2017 for use in patients aged >18 years; the drug has since been approved for patients aged ≥12 years with moderate to severe AD. Biomarker analyses have shown that dupilumab reduces the Th2 response by blocking IL- 4 and IL- 13 signaling.8 Dupilumab inhibits the IL-4 α subunit, having the downstream effect of reducing both IL-4 and IL-13.

Dupilumab is subcutaneously administered by injections either by a healthcare provider or at home.  The initial loading dose of dupilumab is 600 mg, followed by injections of 300 mg administered every other week. Some patients require weekly injections.

According to a recent review by Frampton, et al, phase 3 trial data have proven that 16 weeks of treatment with dupilumab has resulted in significant improvement of AD disease severity in terms of rash intensity, pruritus, sleep disturbance, anxiety and depression, and overall quality of life compared with placebo.9 The vast majority of patients improve with dupilumab, and almost 40% of patients achieve clear or almost clear skin.8

Reports have shown that dupilumab effects are enhanced when it is used in conjunction with topical ointments, especially topical corticosteroids.10

No serious adverse events of dupilumab have been reported in phase 3 clinical trials.11 Some less serious adverse events of dupilumab include injection site reactions, eye problems (redness, swelling, and itching), oropharyngeal pain, upper respiratory tract infections like colds, and some skin infections. Eye symptoms are usually managed with over-the-counter or prescription allergy drops.

In an original research study, Kuznik, et al compared the cost of dupilumab administered every 2 weeks with supportive care.12 The investigators concluded that dupilumab for the management of AD is cost-effective in US adults at an annual price for maintenance therapy of $ 29,000 to 40,000.12

Summary

As AD is a chronic process, long-term treatment with multistep management is required. Patient understanding of disease and adherence to treatment are of utmost importance for controlling the clinical symptoms of AD. Newer, cost-effective medications like dupilumab have shown great efficacy in patients with severe AD. However, more research is required to understand the long-term effects of treatment with the novel biologic agent.

References

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2. Egawa G, Kabashima K. Multifactorial skin barrier deficiency and atopic dermatitis: essential topics to prevent the atopic march. J Allergy Clin Immunol. 2016;138(2):350-358.e1.

3. Weidinger S, Illig T, Baurecht H, et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol. 2006;118:214-219.

4. Levin J, Friedlander SF, Del Rosso JQ. Atopic dermatitis and the stratum corneum: part 3: the immune system in atopic dermatitis. J Clin Aesthet Dermatol. 2013;6(12):37-44.

5. Liu T, Ji R-R. New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms? Pflugers Arch. 2013;465(1):1671-1685.

6. Cevikbas F, Wang X, Akiyama T, et al. A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: Involvement of TRPV1 and TRPA1. J Allergy Clin Immunol. 2014;133(2):448-460.

7. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis.  Section 2: Management and treatment of atopic dermatitis with topical therapies. J Amer Acad Dermatol. 2014;71(1):116-132.

8. Ariëns LFM, Bakker DS, van der Schaft J, Garritsen FM, Thijs JL, de Bruin-Weller MS. Dupilumab in atopic dermatitis: rationale, latest evidence and place in therapy. Ther Adv Chronic Dis. 2018;9(9):159-170.

9. Frampton JE, Blair HA. Dupilumab: a review in moderate-to-severe atopic dermatitis. Am J Clin Dermatol. 2018;19(4):617-624.

10. Rodrigues MA, Nogueira M, Torres T. Dupilumab for atopic dermatitis. Evidence to date

[published online June 17, 2019]

. G Ital Dermatol Venereol. doi: https://doi.org/10.23736/S0392-0488.19.06417-4

11. Eshtiaghi P, Gooderham MJ. Dupilumab: an evidence-based review of its potential in the treatment of atopic dermatitis. Core Evid. 2018;13:13-20.

12. Kuznik A, Bégo-Le-Bagousse G, Eckert L, et al.  Economic evaluation of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults. Dermatol Ther. 2017;7(4):493-505.