Methotrexate, Cyclosporine Yield Lowest Infection Risk in Atopic Dermatitis

Atopic dermatitis (an allergy-related skin disorder) with secondary infection on a patient's wrist.
Atopic dermatitis (an allergy-related skin disorder) with secondary infection on a patient’s wrist.
Patients requiring systemic therapy for atopic dermatitis may benefit from lower infection risk treatments such as methotrexate, cyclosporine.

Methotrexate and cyclosporine are associated with the lowest risks, over the course of 6 months, for serious infections in adults with atopic dermatitis, according to a study published in the Journal of the American Academy of Dermatology. The drugs mycophenolate, azathioprine, and prednisone were associated with an increased risk for serious infection.

This population-based claims study included participants with atopic dermatitis from longitudinal claims data. Cohort 1 included 232,611 individuals and compared new users of biologics with phototherapy, and cohort 2 included 23,908 individuals and compared new users of dupilumab with nonbiologics. Azathioprine, methotrexate, cyclosporine, mycophenolate, and prednisone were chosen as 5 systemic drugs commonly used to treat atopic dermatitis.

International Statistical Classification of Diseases and Related Health Problems diagnostic codes were used to compute the incidence of opportunistic and serious bacterial infections, resulting in hospitalization. The first use of a specified nonbiologic systemic drug constituted the cohort entry date, with follow-up spanning the period from 1 to 180 days after cohort entry. Propensity scores were used to match participants for pair-wise comparisons and relative risks.

Serious infections occurred among 7.53/1000 users of systemic nonbiologic drugs compared with 7.38/1000 among those treated with phototherapy and 2.6/1000 among those using dupilumab. Cyclosporine had a significantly lower 6-month risk for infection than methotrexate (relative risk [RR], 0.87; 95% CI, 0.59-1.29), whereas higher risks were found for prednisone (RR, 1.89; 95% CI, 1.05-3.42), mycophenolate (RR, 3.31; 95% CI, 1.94-5.64), and azathioprine (RR, 1.78; 95% CI, 0.98-3.25). Dupilumab was not associated with greater risk (RR, 0.33; 95% CI, 0.03-3.19), although it was found that dupilumab users had higher prior use of systemic prednisone.

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Limitations to this study include a small number of events, a lack of consideration of specific dosing methods, a lack of data on 6-month dose exposure to medications, and potential low applicability of the results because of the use of systemic prednisone and cyclosporine for flares and induction, rather than long-term management.

The researchers concluded that “cyclosporine and methotrexate appear to have better safety profiles than mycophenolate, azathioprine and systemic prednisone with regard to serious infections. These findings may help inform clinicians in their selection of medications for patients requiring systemic therapy for atopic dermatitis. Preliminary data on newer targeted biologic molecules such as dupilumab were encouragingly showing no increase in risk but need to be confirmed in larger user populations with longer use.”

Author JF Merola reports financial associations with multiple pharmaceutical companies.

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Schneeweiss MC, Perez-Chada L, Merola JF. Comparative safety of systemic immuno-modulatory medications in adults with atopic dermatitis [published online May 31, 2019]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.05.073