Comment on “An evidence-based guide to SARS-CoV-2 vaccination of patients on immunotherapies in dermatology”
Authors: Reinhart Speeckaert, Jo Lambert, Lluís Puig, Marijn Speeckaert, Hilde Lapeere, Sofie De Schepper, Nanja van Geel
Journal: Journal of the American Academy of Dermatology (2021)

To the Editor: We read with great interest the article by Gresham et al1Gresham L.M. Marzario B. Dutz J. Kirchhof M.G. An evidence-based guide to SARS-CoV-2 vaccination of patients on immunotherapies in dermatology.J Am Acad Dermatol. 2021; https://doi.org/10.1016/j.jaad.2021.01.047Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar summarizing the influence of immunotherapies used in dermatology on vaccine-induced immunity. We believe that a more in-depth discussion of rituximab and mycophenolate mofetil is crucial, as both drugs specifically act on B lymphocytes. The literature indicates that these treatments are associated with increased impairments of vaccine-induced responses compared to other immunomodulating/immunosuppressive therapies used in dermatology.2Kim W. Kim S.-H. Huh S.-Y. et al.Reduced antibody formation after influenza vaccination in patients with neuromyelitis optica spectrum disorder treated with rituximab.Eur J Neurol. 2013; 20: 975-980Crossref PubMed Scopus (50) Google Scholar The article by Gresham et al1Gresham L.M. Marzario B. Dutz J. Kirchhof M.G. An evidence-based guide to SARS-CoV-2 vaccination of patients on immunotherapies in dermatology.J Am Acad Dermatol. 2021; https://doi.org/10.1016/j.jaad.2021.01.047Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar cites a study conducted on patients with autoimmune blistering disorders as evidence that rituximab does not affect the humoral response to seasonal influenza vaccination.3Cho A. Bradley B. Kauffman R. et al.Robust memory responses against influenza vaccination in pemphigus patients previously treated with rituximab.JCI Insight. 2017; 2: e93222Crossref PubMed Scopus (48) Google Scholar However, this study recruited only patients who received their last rituximab dose more than 5 months before vaccination (median, 11 months). This time point was deliberately chosen as B lymphocytes start to recover after 5-6 months. In patients receiving rituximab, vaccination responses and the formation of neutralizing antibodies are blunted until naive B cells reappear. Decreased antibody titers for pneumococcal, tetanus, and influenza vaccines have been confirmed following rituximab administration. Therefore, this study cannot be used as evidence that vaccine-induced protection will be adequate in patients receiving rituximab for skin disorders, especially if the vaccine was given earlier than 5 months after the last rituximab dose. Substantial data have confirmed that vaccination should be administered preferably 6 months after the last rituximab dose. The authors reference another study that led to the conclusion that there is "no significant effect of rituximab on humoral response to yellow fever vaccination." However, this study included only 3 patients on rituximab (3/31) and one of them had the lowest antibody titer of all included patients.4Oliveira A.C.V. Mota L.M.H. Santos-Neto L.L. Simões M. Martins-Filho O.A. Tauil P.L. Seroconversion in patients with rheumatic diseases treated with immunomodulators or immunosuppressants, who were inadvertently revaccinated against yellow fever.Arthritis Rheumatol. 2015; 67: 582-583Crossref PubMed Scopus (28) Google Scholar Therefore, we believe that no conclusion can be made about the humoral response to yellow fever vaccination based on this study. For systemic immunotherapeutics, the evidence seems to point to a slightly different risk profile as mentioned in the conclusion of the paper since data indicate that rituximab and mycophenolate mofetil carry a higher propensity for reducing antibody levels compared to methotrexate, Janus kinase (JAK) inhibitors, and systemic corticoids (Fig 1). The authors correctly mention that, although diminished, satisfactory immune responses to vaccination are reached in most JAK inhibitor-treated patients. The authors recommend temporarily withdrawing the drug 2-3 weeks before vaccination; however, it is unclear if this approach is effective. Only 1 cited paper mentions withdrawal of JAK inhibitors and temporary discontinuation did not improve vaccine-induced response rates to pneumococcal polysaccharide vaccine (continuous vs withdrawal; 75.0% vs 84.6%, respectively) or influenza (66.3% vs 63.7%, respectively).5Winthrop K.L. Silverfield J. Racewicz A. et al.The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis.Ann Rheum Dis. 2016; 75: 687-695Crossref PubMed Scopus (157) Google Scholar As most patients were also receiving methotrexate and the subgroup of patients treated with JAK inhibitors alone was relatively small, there may be effects on T cell responses that were not captured by these data. Nonetheless, there is little evidence to recommend the temporary withdrawal of JAK inhibitors before SARS-CoV-2 vaccination. None disclosed. An evidence-based guide to SARS-CoV-2 vaccination of patients on immunotherapies in dermatologyJournal of the American Academy of DermatologyVol. 84Issue 6PreviewImmune-mediated diseases and immunotherapeutics can negatively affect normal immune functioning and, consequently, vaccine safety and response. The COVID-19 pandemic has incited research aimed at developing a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. As SARS-CoV-2 vaccines are developed and made available, the assessment of anticipated safety and efficacy in patients with immune-mediated dermatologic diseases and requiring immunosuppressive and/or immunomodulatory therapy is particularly important. Full-Text PDF Response to comment on "An evidence-based guide to SARS-Cov-2 vaccination of patients on immunotherapies in dermatology."Journal of the American Academy of DermatologyVol. 85Issue 2PreviewTo the Editor: We would like to thank Speeckaert et al for their thoughtful comments on our article. We appreciate the authors' attention to detail in noting that in the study by Cho et al,1 although rituximab exposure did not significantly affect the humoral response to seasonal influenza vaccination in patients with autoimmune blistering disease, the interpretation was limited as rituximab treatment had been discontinued for at least 5 months prior to the vaccination.1 Based on the study of ocrelizumab (a humanized anti-CD20 antibody),2 Waldman et al3 have suggested the timing of the vaccination to be at least 4 weeks prior to anti-CD20 administration, and/or vaccinating the patients 12-20 weeks after a treatment cycle. Full-Text PDF