Management options in patients with atopic dermatitis refractory to topical therapies

Most people with atopic dermatitis (AD) can gain sufficient control by using emollients and prescription topical therapies. However, patients with more severe or widespread disease, those with substantially impaired quality of life and individuals with AD that is refractory to optimized topical therapy may require phototherapy or systemic therapies to improve disease control and quality of life. To assist in managing patients with more advanced disease, the American Academy of Dermatology has updated its 2014 evidence-based recommendations for management of atopic dermatitis (AD) with phototherapy and systemic therapies, including oral medications (immunosuppressants, corticosteroids, antimetabolites, Janus kinase [JAK] inhibitors) and injectable medications (biologics). The multidisciplinary workgroup that developed the guidelines was U.S.-based, but included Dr. Aaron Drucker, Division of Dermatology, Department of Medicine, University of Toronto, who is also with the Women’s College Research Institute, Women’s College Hospital in Toronto. Recommendations in the guidelines are summarized below, with each recommendation followed by the strength of the recommendation and the certainty of the evidence: Phototherapy Phototherapy (all types) is conditionally recommended for adults with AD. (Strength of recommendation–Conditional; Certainty of evidence–Low). Most current literature has reported on the efficacy and safety of narrow band UVB. Wherever possible, use a light source that minimizes the potential for harm, under the supervision of a qualified clinician. Monoclonal antibodies (biologics) Dupilumab is recommended for adults with moderate to severe AD. (Strong; Moderate) Tralokinumab is recommended for adults with moderate to severe AD. (Strong; Moderate) JAK inhibitors Upadacitinib is recommended for adults with moderate to severe AD. (Strong; Moderate) Note that upadacitinib is approved in patients with AD who have failed other systemic therapies (pills or injections, including biologics) or when use of those therapies is inadvisable. Abrocitinib is recommended for adults with moderate to severe AD. (Strong; Moderate). Abrocitinib is approved in patients with AD who have failed other systemic therapies (pills or injections, including biologics) or when use of those therapies is inadvisable. Baricitinib (off-label) is recommended for adults with moderate to severe AD. (Strong; Moderate) Antimetabolite Methotrexate (off-label) is conditionally recommended for adults with moderate to severe AD, with proper monitoring. (Conditional; Low). Methotrexate may be inappropriate for select patients due to comorbidities or drug interactions that may exacerbate toxicity. Immunosuppressants Systemic corticosteroids (e.g., prednisone). The guidelines conditionally recommend against systemic corticosteroids. (Conditional; Low). Their use should be reserved for acute severe exacerbations and as a short-term bridge therapy to other systemic corticosteroid-sparing therapy. Mycophenolate mofetil (off-label) is conditionally recommended for adults with refractory moderate to severe AD, with proper monitoring. (Conditional; Very low). It may be inappropriate for select patients due to comorbidities or drug interactions that may exacerbate toxicity. Azathioprine (off-label) is conditionally recommended for adults with refractory moderate to severe AD, with proper monitoring. (Conditional; Low). It may be inappropriate for select patients due to comorbidities or drug interactions that may exacerbate toxicity. Cyclosporine (off-label). Limited-term use of cyclosporine for adults with refractory moderate to severe AD is conditionally recommended, with proper monitoring. (Conditional; Low). In the United States, cyclosporine is approved for limited-term use (up to 1 year) in psoriasis. It may be inappropriate for select patients due to comorbidities or drug interactions that may exacerbate toxicity. The updated guidelines include a dosing table for all of the systemic drug therapies. The guidelines note that data are currently insufficient to make recommendations regarding the use of PUVA phototherapy, systemic antibiotics, oral antihistamines, montelukast, apremilast, ustekinumab, intravenous immunoglobulin, interferon gamma, omalizumab, tumour necrosis-alpha inhibitors, systemic calcineurin inhibitors (other than cyclosporine) or mepolizumab in the management of AD. The use of systemic antibiotics should be limited to situations of clinically evident infection. The authors comment that larger clinical trials are needed for cyclosporine, methotrexate, azathioprine and mycophenolate to improve the certainty of evidence for these medications. In addition, formal cost-effectiveness analyses comparing older to newer treatments are needed. As new systemic therapies continue to be developed, the authors encourage the use of active comparator arms in randomized controlled trials, rather than relying solely on placebo-controlled trials. Active comparators enable a better understanding of how new treatments fit into the current treatment paradigm. The authors endorse continuous monitoring of the long-term safety of systemic medications with rigorous pharmacovigilance studies. Studies evaluating the risk of venous thromboembolism, cardiovascular events and cancer associated with JAK inhibitors are also necessary. Summary For adults with moderate to severe AD, the guidelines make strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib (off-label) and upadacitinib. Conditional recommendations are made in favour of the use of phototherapy, cyclosporine (off-label), methotrexate (off-label), azathioprine (off-label) and mycophenolate (off-label), and against the use of systemic corticosteroids. The use of phototherapy and systemic therapies to manage AD in children will be covered in a forthcoming guideline. Reference 1. Davis DMR, Drucker AM, Alikhan A, et al. Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies. Am Acad Dermatol 2023; published online November 3, 2023. (accessed November 16, 2023).

Management options in patients with atopic dermatitis refractory to topical therapies

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