In Dermatology Patients, Immunomodulators May Need Adjustment During the Pandemic

By Marilynn Larkin

April 14, 2020

NEW YORK (Reuters Health) - Immunomodulatory therapies for dermatologic conditions that impact the body's ability to fight viruses require extra precaution during the pandemic, and in some cases, modifications, researchers suggest.

Two papers published in the Journal of the American Academy of Dermatology address the use of immunomodulatory therapies. In the first paper, Dr. John Zampella and Payal Shah of New York University School of Medicine expand upon recent guidelines from the academy. (https://bit.ly/2UvGq2c).

"The American Academy of Dermatology recommended against stopping these medicines in patients who are already on them, and if patients have severe diseases requiring these medicines, not to withhold treatment," Dr. Zampella told Reuters Health by email. "We emphasized avoiding medications that inhibit molecular pathways involved in the immune system's ability to fight off viruses. Inhibiting other pathways may be less worrisome."

In their paper, they note that biologic therapies that modulate and blunt Th1 responses, including TNF-alpha inhibitors, abatacept (CTLA-4 inhibitor), and ustekinumab (IL-12/23 inhibitor) may require more stringent precautions to diminish the risk of infection, and so alternative therapies should be prioritized when possible.

Similar precautions should be taken with non-biologic therapies, such as cyclosporine, azathioprine, and methotrexate, since they create a state of generalized immunosuppression, they suggest.

In addition, Dr. Zampella and Shah note that paradoxically, "further deterioration in infected patients may be the result of a proinflammatory state created by a cytokine storm, suggesting that a subset of immunotherapies may actually play a protective role in patients with SARS-CoV-2 infection by inhibiting the intensity of the cytokine storm."

Dr. Adam Friedman, Interim Chair of Dermatology and Director of the Supportive Oncodermatology Clinic at George Washington School of Medicine and Health Science in Washington, DC, commented by email, "The authors raise a commonly overlooked component to life-threatening infections: Is it the infection or the resulting inflammatory storm that is the source of morbidity and mortality? The answer is the latter, which is the reason systemic steroids are often part of a hospital's sepsis protocol."

"While it is plausible that many of the medications we use so routinely could increase infection risk, so too could they potentially be protective," he said. "One therapeutic approach being evaluated for the management of COVID-19 infection is nitric oxide, which can have a dichotomous biological role in both killing pathogens/being pro-inflammatory as well as being anti-inflammatory/pro-resolution of damaging inflammation."

"For now," he noted, "my approach has been to maintain patients on their biologics and immunosuppressants but with strict guidance with respect to hand washing, social distancing, and close communication with me via telehealth platforms."

In the second paper, Dr. Alessia Villani of the University of Naples and colleagues report their experience in managing 37 patients (median age, 75) with advanced basal cell carcinoma on sonic hedgehog inhibitor therapy during the outbreak. Nine were treated with sonidegib, and 28, with vismodegib. The median treatment duration was 4.4 months. All patients responded to treatment, with partial (from 25% to 75%) and almost complete (>75%) remission.

Teleconsultations were provided to help patients stay on therapy and avoid infection. Eight (89%) patients on sonidegib went to an outpatient clinic for their mandatory monthly drug prescription. By contrast, 19 (68%) on vismodegib did not go to the clinic and continued treatment with a dose adjustment.

"In three patients, considered high-risk...for the presence of severe comorbidities, we favored discontinuation," they noted.

"Teledermatology could be a useful tool for taking care of our patients during this pandemic period to avoid treatment discontinuation and to prevent the worsening of skin diseases," Dr. Villani told Reuters Health by email. "As proposed in the article, patients with a good response to treatment could also decide to modify the treatment (regimen) in order to prolong therapy duration."

Dr. Zampella commented on the study, noting that, from a pathophysiologic standpoint, "the sonic hedgehog pathway may be involved in early stages of T-cell maturation; however, it has less of a role later on. So other than the general immunosuppression from having a cancer or getting chemotherapy, this medicine may be less worrisome than other chemotherapies or immunomodulating therapies that directly impact the body's ability to fight viruses."

SOURCE: https://bit.ly/2Vfasq2 and https://bit.ly/2Vjeuh9 Journal of the American Academy of Dermatology, online March 31, 2020.

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