COVID-19 and immunomodulator/immunosuppressant use in dermatology

Abstract

To the Editor: We read with great interest the Commentary by Lebwohl et al1Lebwohl M. Rivera-Oyola R. Murrell D.F. Should biologics for psoriasis be interrupted in the era of COVID-19?.J Am Acad Dermatol. 2020; 82: 1217-1218Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar recently published in the Journal of the American Academy of Dermatology. The authors provided a pertinent overview of infection risk associated with commonly used biologics to treat psoriasis in light of the current coronavirus disease 2019 (COVID-19) outbreak. We agree that this time has been particularly concerning for patients taking immunomodulators/immunosuppressants who are unsure of their risk for severe disease. In response to the previous commentary, the goal of this letter is to expand and provide the latest information about COVID-19 along with considerations for addressing patient concerns surrounding dermatology-related immunomodulator/immunosuppressant use. Theoretical data from previous coronavirus outbreaks has suggested a strong role for type I interferon, B-cell–released antibodies, tumor necrosis factor-α, and other cytokines in the viral immune response (Fig 1).2Rothan H.A. Byrareddy S.N. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak.J Autoimmun. 2020; : 102433Crossref PubMed Scopus (2853) Google Scholar, 3Prompetchara E. Ketloy C. Palaga T. Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic.Asian Pac J Allergy Immunol. 2020; 38: 1-9PubMed Google Scholar, 4Li G. Fan Y. Lai Y. et al.Coronavirus infections and immune responses.J Med Virol. 2020; 92: 424-432Crossref PubMed Scopus (1095) Google Scholar Interleukin (IL) 17 cytokines are important for immune cell recruitment to infection sites to promote clearance, while also activating downstream cascades of cytokines and chemokines.4Li G. Fan Y. Lai Y. et al.Coronavirus infections and immune responses.J Med Virol. 2020; 92: 424-432Crossref PubMed Scopus (1095) Google Scholar IL-1 promotes fever and the differentiation of T-helper cells to IL-17–producing T cells. Tumor necrosis factor-α promotes dendritic cell differentiation, leukocyte recruitment, and mediates fever.4Li G. Fan Y. Lai Y. et al.Coronavirus infections and immune responses.J Med Virol. 2020; 92: 424-432Crossref PubMed Scopus (1095) Google Scholar Antibodies produced by plasma cells help to neutralize the virus, limit infection, and prevent future infections. Disruption of B-cell differentiation into plasma cells could limit antibody production.3Prompetchara E. Ketloy C. Palaga T. Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic.Asian Pac J Allergy Immunol. 2020; 38: 1-9PubMed Google Scholar Broad immunosuppression across multiple cytokine axes with immunosuppressants has the potential to increase susceptibility, persistence, and reactivation of viral infections. Immunosuppressants decrease cytokines that recruit and differentiate immune cells needed to clear the infection. In addition, inflammatory mediators can become hyperactivated, resulting in a “cytokine storm,” which is the primary cause of death in severe disease.3Prompetchara E. Ketloy C. Palaga T. Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic.Asian Pac J Allergy Immunol. 2020; 38: 1-9PubMed Google Scholar Whether withdrawal of broadly immunosuppressive therapies may increase the risk of precipitating cytokine storm is unknown. Therefore, classic immunosuppressants may present the most concerning risk for those affected by COVID-19 (Table I). Immunomodulators, such as biologics, that do not target vital domains within the viral immune response may dampen, but not significantly affect viral clearance.Table IConsiderations for commonly used immunomodulators and immunosuppressants for dermatologic conditionsDrug classMechanism of actionDrug nameRiskComments/considerations∗General considerations only, medication use should be considered based on each individual patient's risk and disease profile.Classic immunosuppressantsInhibits NF-κBCorticosteroidsLikely concerning riskConsider stopping when viral symptoms present especially with known or potential exposureCalcineurin inhibitorTacrolimusCyclosporine AntimetabolitesInhibits DNA replicationMycophenolate mofetilAzathioprineMethotrexateImmunomodulators Monoclonal antibodiesTNF-α inhibitionInfliximabLikely moderate riskContinue if viral symptoms are mild, consider stopping if viral symptoms worsen or high fever develops Receptor fusion proteinEtanercept Monoclonal antibodiesCertolizumab Monoclonal antibodiesAdalimumab IL receptor modulatorsIL inhibitionAnakinra (IL-1) Monoclonal antibodiesDupilumab (IL-4)Likely low riskContinue unless severe symptoms present Monoclonal antibodiesBrodalumab (IL-17)Likely moderate riskContinue if viral symptoms are mild, consider stopping if viral symptoms worsen or high fever develops Monoclonal antibodiesSecukinumab (IL-17a) Monoclonal antibodiesIxekizumab (IL-17a) Monoclonal antibodiesUstekinumab (IL-12/23) Monoclonal antibodiesGuselkumab (IL-23) Monoclonal antibodiesAnti-CD20 antibodyRituximabLikely concerning riskConsider stopping when viral symptoms present especially with known or potential exposure.PDE4 inhibitionApremilastLikely low riskContinue unless severe symptoms presentIL, Interleukin; NF-κB, nuclear factor κB; PDE4, phosphodiesterase 4.∗ General considerations only, medication use should be considered based on each individual patient's risk and disease profile. Open table in a new tab IL, Interleukin; NF-κB, nuclear factor κB; PDE4, phosphodiesterase 4. Currently, there are no data describing the benefits or risks of stopping immunomodulators/immunosuppressants during the COVID-19 outbreak. However, each medication's mechanism of action, administration method/frequency, and pharmacokinetics/pharmacodynamics are important to consider. Nonbiologic medications, including small molecule inhibitors and immunosuppressants, are typically easier to stop and restart within days to weeks due to shorter half-life. Meanwhile, biologics generally have a longer half-life and include a risk of antidrug antibody formation with treatment cessation and subsequent continuation. However, biologics also tend to be more targeted and less involved in the previously mentioned components of the viral immune response. General medication considerations are included in Table I. Although patient dependent, clinicians may consider weaning patients with stable disease off of immunosuppressants. Shared decision making is needed when deciding on a treatment plan that includes immunomodulators/immunosuppressants during the COVID-19 outbreak. Patients with existing comorbidities may require more conservative measures.5Centers for Disease Control and PreventionCoronavirus (COVID-19).https://www.cdc.gov/coronavirus/2019-ncov/index.htmlDate accessed: March 9, 2020Google Scholar Physicians should continue to consult with the Centers for Disease Control and Prevention Information for Healthcare Providers, which is updated daily (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html). Once again, we thank the authors for raising awareness of patient concerns during this evolving outbreak. Should biologics for psoriasis be interrupted in the era of COVID-19?Journal of the American Academy of DermatologyVol. 82Issue 5PreviewTo the Editor: With daily media warnings of a looming pandemic, physicians are understandably concerned about immunosuppressive or immunomodulating effects that might render patients receiving biologic therapies more susceptible to COVID-19 infection. At this early stage, we do not have specific data about susceptibility to the virus, but we have data on infectious complications for biologic therapies from their pivotal trials for psoriasis. Full-Text PDF