Management of Systemic Immunomodulators During the COVID-19 Pandemic
An understanding of pathophysiology may serve to guide clinical decision making when using biologic agents during the COVID-19 pandemic.
Known data may serve as guidance for the use of biologic agents prescribed to treat patients with dermatologic issues amid the coronavirus disease 2019 (COVID-19) pandemic, according to a letter published in the Journal of the American Academy of Dermatology.1 The letter was a response to the American Academy of Dermatology’s publication, “Guidance on the use of biologic agents during COVID-19 outbreak.”2
The authors acknowledged that no data currently exist on the immunopathophysiology of biologic agents in patients infected with this specific virus, but existing data may point to those biologic therapies requiring “extra precautions to mitigate COVID-19 morbidity.” Although it is known that older patients, patients with serious chronic medical conditions, and patients who are immunosuppressed because of prior or current cancer represent populations at risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection — in whom prevention is a considerable tool to reduce risk — it is not yet established if patients treated with biologic agents and small molecule therapies are part of this at-risk population.
An understanding of the physiology and mechanisms of biologic agents can facilitate physician-patient collaboration in treatment decision making, the authors suggested, in patients who require immunosuppressive and immunomodulatory therapies to manage inflammatory and autoimmune disorders.
A key defense against viral pathogens is CD4+ T-cell immunity, and Th17, Th2, and Treg cell populations may be produced to fight infection against some viral pathogens. As tumor necrosis factor-alpha inhibitors such as abatacept and ustekinumab modulate and blunt Th1 responses, the authors suggested that these therapies be closely monitored in patients to reduce the risk for infection and other treatment options be pursued, if possible. Other treatments that should be used with caution include interleukin-17 inhibitors and dupilumab, as their effect on SARS-CoV-2 has not yet been defined. The immunosuppressive effects of the nonbiologic systemic therapies cyclosporine, azathioprine, and methotrexate imply that they should also be used with caution and other therapies considered.
A proinflammatory state created by a cytokine storm may be responsible for the advanced deterioration seen in infected patients, data suggest, and a similar disease pattern was noted in SARS-CoV and MERS-CoV. A subset of immunosuppressive therapies are suspected of having a protective effect in infected patients, as suggested by the cytokine storm immunopathology of SARS-CoV-2. Lung tissue damage and further clinical deterioration may be prevented by the immunosuppressant agents’ inhibition of an intense cytokine storm.
As clinical evidence is collected to inform evidenced-based guidelines for management of COVID-19, the authors wrote, “…dermatologists should use their clinical judgment, the existing AAD guidelines, and an understanding of pathophysiology to determine the appropriate risk-benefit of using systemic immunomodulating therapies.”
References
1. Shah P, Zampella, JG. Use of systemic immunomodulatory therapies during the coronavirus disease 2019 (COVID-19) pandemic [published online March 31, 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2020.03.056
2. American Academy of Dermatology. Guidance on treating patients with biologics. https://www.aad.org/member/practice/coronavirus/clinical-guidance/biologics. Accessed April 9, 2020.
