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Methotrexate and cyclosporine appear to have better safety profiles over a six-month period than other systemic treatments used to treat atopic dermatitis, according to a recent study.
Methotexate and cyclosporine appear to have better safety profiles over a six-month period than other systemic treatments used to treat atopic dermatitis, according to the results of a study published in the Journal of the American Academy of Dermatology.1
Researchers at Brigham and Women’s Hospital in Boston analyzed insurance claims data to determine and compare rates of occurrence of serious bacterial and opportunistic infections among patients taking the drugs for atopic dermatitis in real-life practice.
They examined five non-biologic systemic drugs that are often used off-label: methotrexate, cyclosporine, azathioprine, prednisone and mycophenolate. They also examined phototherapy and dupilumab (Dupixent, Sanofi and Regeneron Pharmaceuticals), the only targeted biologic drug specifically approved for atopic dermatitis. Phototherapy is generally considered a safe treatment option for patients with recalcitrant atopic dermatitis, with most of its safety evidence coming from use in patients with psoriasis.2
Cyclosporine and methotrexate were associated with the lowest rates of serious infections, while prednisone, azathioprine and mycophenolate were associated with higher infection rates.1 The small amount of available data on dupilumab did not suggest any safety concerns, but the researchers pointed out that since dupilumab has been marketed in the United States since March 28, 2017, a more in-depth evaluation is needed.
The claims data covered 185 million patients in the United States between 2003 and 2017. Patients aged 18 or older with a diagnosis of atopic dermatitis who had not taken an immunomodulating agent in the six months prior to initiation of treatment were included. Patients were excluded if they had started a systemic immunomodulatory drug for reasons other than atopic dermatitis, such as rheumatoid arthritis, connective tissue disease, psoriasis, inflammatory bowel disease, cancer or HIV.
Patients were followed up to six months from treatment initiation for events of serious bacterial infections, such as cellulitis and abscess, septicemia and bacteremia, pneumonia or opportunistic infections, such as pulmonary tuberculosis, listeriosis and leishmaniasis that led to hospital admission.
Data on 232,611 patients were analyzed, and these showed that the incidence of serious infections was 7.53 per 1,000 (95% confidence interval 7.18-7.89) among patients treated with systemic non-biologics, 7.38 per 1,000 (95% confidence interval 5.68-9.57) among patients treated with phototherapy, and 2.6 per 1,000 (95% confidence interval 0.45-14.3) among dupilumab users.
Regression analysis was used to compare infection rates of the drugs to infection rates with methotrexate. Results showed that cyclosporine had a significantly reduced six-month risk (RR =0.87), while prednisone, azathioprine and mycophenolate showed increased risks (RR = 1.78, 1.89 and 3.31, respectively).
“These findings may help inform clinicians in their selection of medications for patients requiring systemic therapy for atopic dermatitis,” says Joseph Merola, M.D., department of dermatology, Brigham and Women’s Hospital and division of pharmacoepidemiology, department of medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston.
However, cyclosporine and systemic prednisone are typically used for induction and flares rather than long-term maintenance, which may have impacted the results, he says, and cyclosporine duration may be limited by other long-term toxicities considerations, such as nephrotoxicity.
Data on serious infection rates in the small numbers of dupilumab users were compared with those for methotrexate (relative risk =0.33; 0.03 - 3.20), and “encouragingly showed no increase in risk,” Dr. Merola says. However, he adds that this would need to be confirmed in larger user populations with longer use.
As dupilumab was only marketed in the United States from late March 2017, it could only be evaluated on preliminary 2017 data. That data showed one event among 391 patients. “This analysis is limited but does not show an obvious signal for increased risk,” Dr. Merola says.
1. Schneeweiss MC, Perez-chada L, Merola JF. Comparative Safety of Systemic Immuno-modulatory Medications in Adults with Atopic Dermatitis. J Am Acad Dermatol. 2019;
2. Patrizi A, Raone B, Ravaioli GM. Management of atopic dermatitis: safety and efficacy of phototherapy. Clin Cosmet Investig Dermatol. 2015;8:511-20.
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