Toward a COVID-19 vaccine strategy for patients with pemphigus on rituximab
Authors: Reid A. Waldman, Marina Creed, Kelley Sharp, Jonas Adalsteinsson, Jaime Imitola, Timothy Durso, Jun Lu
Journal: Journal of the American Academy of Dermatology (2020)

To 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. The effect of rituximab and other anti-CD20 monoclonal antibodies on vaccine response has been studied for inactivated vaccines, including those for seasonal influenza, hepatitis B, tetanus, shingles, pneumococcus, and Haemophilus influenzae type b.1Baker D. Roberts C.A.K. Pryce G. et al.COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases.Clin Exp Immunol. 2020; 202: 149-161Crossref PubMed Scopus (160) Google Scholar,2Houot R. Levy R. Cartron G. Armand P. Could anti-CD20 therapy jeopardise the efficacy of a SARS-CoV-2 vaccine?.Eur J Cancer. 2020; 136: 4-6Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar These studies suggest that rituximab recipients mount attenuated yet meaningful vaccine responses.1Baker D. Roberts C.A.K. Pryce G. et al.COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases.Clin Exp Immunol. 2020; 202: 149-161Crossref PubMed Scopus (160) Google Scholar Additionally, these studies indicate that rituximab recipients are not at increased risk of inactivated vaccine-related adverse effects.3Mohme S. Schmalzing M. Müller C.S.L. Vogt T. Goebeler M. Stoevesandt J. Immunizations in immunocompromised patients: a guide for dermatologists.J Dtsch Dermatol Ges. 2020; 18: 699-723Google Scholar Recently, a prospective clinical trial evaluated the effect of ocrelizumab (humanized anti-CD20 antibody) on the immunogenicity of several vaccines that were administered 12 weeks after infusion.4Bar-Or A. Calkwood J.C. Chognot C. et al.Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: the VELOCE study.Neurology. 2020; 95: e1999-e2008Crossref PubMed Scopus (253) Google Scholar This study showed increased seroprotection rates across all studied vaccines in ocrelizumab recipients, although these conversion rates are lower than those observed in control individuals. Consensus guidelines recommend administering routine vaccinations (eg, tetanus, diphtheria, and pertussis [TDaP]) at least 4 weeks before rituximab initiation.3Mohme S. Schmalzing M. Müller C.S.L. Vogt T. Goebeler M. Stoevesandt J. Immunizations in immunocompromised patients: a guide for dermatologists.J Dtsch Dermatol Ges. 2020; 18: 699-723Google Scholar Notably, they recommend administering inactivated influenza vaccine even in individuals undergoing active treatment with rituximab, because patients face imminent risk of contracting influenza, which outweighs the minimal risks associated with vaccination.3Mohme S. Schmalzing M. Müller C.S.L. Vogt T. Goebeler M. Stoevesandt J. Immunizations in immunocompromised patients: a guide for dermatologists.J Dtsch Dermatol Ges. 2020; 18: 699-723Google Scholar Importantly, there are no studies addressing the immunogenicity of live attenuated vaccines, given theoretical safety concerns regarding the use of live attenuated vaccines in rituximab recipients.3Mohme S. Schmalzing M. Müller C.S.L. Vogt T. Goebeler M. Stoevesandt J. Immunizations in immunocompromised patients: a guide for dermatologists.J Dtsch Dermatol Ges. 2020; 18: 699-723Google Scholar Additionally, there are no studies that have evaluated the safety and immunogenicity of messenger RNA vaccines or viral vector vaccines, which are among the leading COVID-19 vaccine candidates, because no vaccines in these classes are commercially available. How should dermatologists approach vaccination of rituximab recipients with a future COVID-19 vaccine? Although the answer will depend on the type(s) of vaccine(s) that reach the market, inoculation with vaccines that do not contain live virus particles (eg, inactivated vaccines, messenger RNA vaccines) should be considered in the absence of postmarketing data or vaccine trial signals suggesting previously unforeseen risk.5Pardi N. Hogan M.J. Porter F.W. Weissman D. mRNA vaccines—a new era in vaccinology.Nat Rev Drug Discov. 2018; 17: 261-279Crossref PubMed Scopus (2560) Google Scholar We assess that COVID-19 vaccine recommendations similar to influenza vaccine recommendations are sensible until COVID-19 vaccine response data for individuals receiving rituximab emerges. The ideal timing of vaccination is unknown; however, individuals who have not initiated rituximab therapy are typically vaccinated at least 4 weeks before rituximab infusion. Individuals who are actively receiving rituximab are often vaccinated against influenza 12 to 20 weeks after completion of a treatment cycle so that patients have 4 weeks or longer before their next infusion (assuming dosing every 6 months) to mount an immune response.3Mohme S. Schmalzing M. Müller C.S.L. Vogt T. Goebeler M. Stoevesandt J. Immunizations in immunocompromised patients: a guide for dermatologists.J Dtsch Dermatol Ges. 2020; 18: 699-723Google Scholar Extending rituximab dosing intervals to enhance vaccine response should be weighed against the risk of disease recurrence. Although vaccine response may be attenuated and may occur at lower rates in rituximab recipients, vaccine response can be quantified with titers, which may be helpful for guiding decisions to revaccinate patients after humoral immune reconstitution (approximately 6-9 months after rituximab discontinuation). Until COVID-19 vaccines arrive, the data encourage careful use of anti-CD20 therapy for skin disease. When vaccines are available, dermatologists can consider vaccinating patients 12 to 20 weeks after the completion of a treatment cycle or extending rituximab dosing intervals. 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 Reply to "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 letter by Shakshouk et al, "Treatment Considerations for Patients With Pemphigus During the COVID-19 Pandemic."1 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. Full-Text PDF