Reply to “Treatment considerations for patients with pemphigus during the COVID-19 pandemic”
Authors: Brittney Schultz, David R. Pearson, Matthew Mansh
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: We read with interest the letter by Shakshouk et al, "Treatment Considerations for Patients With Pemphigus During the COVID-19 Pandemic."1Shakshouk H. Daneshpazhooh M. Murrell D.F. Lehman J.S. Treatment considerations for patients with pemphigus during the COVID-19 pandemic.J Am Acad Dermatol. 2020; 82: e235-e236Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar We agree with careful consideration of treatment for patients with pemphigus during this unprecedented pandemic. Rather than delaying all rituximab infusions, however, we advocate that rituximab be discussed and considered individually through shared decision making. In particular, rituximab should be considered for patients with severe disease and without active coronavirus disease 2019 (COVID-19) illness after discussion of specific individual-level risks (age, comorbidities, and occupation) and benefits of rituximab. We would also consider rituximab for younger patients without comorbidities and with less severe disease. First, rituximab is an effective and targeted therapy for pemphigus. We have limited data directly comparing adverse events in patients treated with rituximab versus other therapies, but compared with prednisone alone, rituximab plus short-term prednisone resulted in decreased cumulative exposure to prednisone and fewer adverse effects,2Joly P. Maho-Vaillant M. Prost-Squarcioni C. et al.First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial.Lancet. 2017; 389: 2031-2040Abstract Full Text Full Text PDF PubMed Scopus (404) Google Scholar including known risk factors for COVID-193Hu L. Chen S. Fu Y. et al.Risk factors associated with clinical outcomes in 323 COVID-19 hospitalized patients in Wuhan, China.Clin Infect Dis. 2020; (https://doi.org/10.1093/cid/ciaa539)Google Scholar: diabetes mellitus requiring insulin and major weight gain. Because of its superior efficacy, as well as uncertainty about pandemic length and time to develop an effective vaccine, rituximab has the potential to result in better patient outcomes while reducing cumulative immunosuppression throughout the pandemic. Second, the risk of COVID-19 infection and its associated outcomes after rituximab treatment is concerning but unknown. Although this represents only a single case, 1 patient with granulomatosis with polyangiitis who developed COVID-19 1 month after rituximab treatment and while receiving low-dose prednisone and methotrexate had a full recovery.4Fallet B. Kyburz D. Walker U.A. Mild course of coronavirus disease 2019 and spontaneous severe acute respiratory syndrome coronavirus 2 clearance in a patient with depleted peripheral blood B-cells due to treatment with rituximab.Arthritis Rheumatol. 2020; (https://doi.org/10.1002/art.41380)PubMed Google Scholar Furthermore, rituximab may be protective against severe COVID-19 infection because antiviral IgG has been shown to induce severe lung injury in COVID-19 illness and patients treated with rituximab may be less able to develop antiviral IgG, as in the above-mentioned case.4Fallet B. Kyburz D. Walker U.A. Mild course of coronavirus disease 2019 and spontaneous severe acute respiratory syndrome coronavirus 2 clearance in a patient with depleted peripheral blood B-cells due to treatment with rituximab.Arthritis Rheumatol. 2020; (https://doi.org/10.1002/art.41380)PubMed Google Scholar Additionally, T-cell response to viral antigens can still occur after rituximab treatment.4Fallet B. Kyburz D. Walker U.A. Mild course of coronavirus disease 2019 and spontaneous severe acute respiratory syndrome coronavirus 2 clearance in a patient with depleted peripheral blood B-cells due to treatment with rituximab.Arthritis Rheumatol. 2020; (https://doi.org/10.1002/art.41380)PubMed Google Scholar Conversely, physicians should discuss that rituximab may reduce immunoresponse to vaccination,5Friedman M.A. Winthrop K.L. Vaccines and disease-modifying antirheumatic drugs: practical implications for the rheumatologist.Rheum Dis Clin North Am. 2017; 43: 1-13Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar which may decrease the ability of patients to effectively receive a COVID-19 vaccine. The response to vaccination appears to improve when given 6 months or more after rituximab dosing.5Friedman M.A. Winthrop K.L. Vaccines and disease-modifying antirheumatic drugs: practical implications for the rheumatologist.Rheum Dis Clin North Am. 2017; 43: 1-13Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar Immunoresponse to infection itself may similarly be blunted, theoretically leading to risk of reinfection. In summary, we agree with careful consideration of rituximab for patients during the COVID-19 pandemic. However, with an unknown peak of COVID-19, it may not be feasible or beneficial to delay rituximab. On an individualized basis through shared decision making, dermatologists should consider rituximab for select patients. Our approach is to discuss rituximab for patients with severe disease who might otherwise require high doses of prednisone or more broadly immunosuppressive agents over an extended period, and for those with less severe disease but fewer comorbidities and younger age. Rheumatologic dosing of rituximab, rather than hematologic, can be considered to decrease health care exposures, and we would recommend against maintenance dosing in stable patients for whom the risk of disease flare is deemed low.2Joly P. Maho-Vaillant M. Prost-Squarcioni C. et al.First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial.Lancet. 2017; 389: 2031-2040Abstract Full Text Full Text PDF PubMed Scopus (404) Google Scholar Before rituximab is used, we recommend discussing vaccination concerns and general infection control guidance, including social distancing, frequent hand washing, and use of masks. Treatment considerations for patients with pemphigus during the COVID-19 pandemicJournal of the American Academy of DermatologyVol. 82Issue 6PreviewTo the Editor: COVID-19, a serious pulmonary illness caused by the highly contagious novel coronavirus, severe acute respiratory syndrome (SARS) coronavirus 2, is a global pandemic. COVID-19–related mortality risk factors include advanced age, male sex, and certain comorbidities, including immunosuppression.1 Besides direct viral-induced injury, the host cytokine-mediated antiviral response potentiates tissue damage.1 Full-Text PDF Authors' reply to the comment "Treatment considerations for patients with pemphigus during the COVID-19 pandemic"Journal of the American Academy of DermatologyVol. 84Issue 1PreviewTo the Editor: We read with interest the thoughtful reply by Schultz et al to our previous correspondence regarding treatment considerations for patients with pemphigus during the coronavirus disease 2019 (COVID-19) pandemic.1 There is established agreement about the need to use caution when approaching iatrogenic immunosuppression, as is usually required in the management of pemphigus. Early in the pandemic, we had suggested postponing rituximab infusions when feasible, given the temporarily irreversible nature of B-cell depletion caused by rituximab, as well as the unknown effect of rituximab on susceptibility to and severity of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Full-Text PDF Toward a COVID-19 vaccine strategy for patients with pemphigus on rituximabJournal of the American Academy of DermatologyVol. 84Issue 4PreviewTo the Editor: Shakshouk et al and Schultz et al discuss the potential impact of rituximab-induced peripheral B-cell depletion on future COVID-19 vaccine response. Their articles highlight the need for emergent study of anti-CD20 therapy's impact on COVID-19 vaccine response. Here, we review existing data surrounding the vaccination of individuals receiving anti-CD20 monoclonal antibodies. Full-Text PDF