Efficacy and safety of anti-COVID-19 vaccination in patients with autoimmune blistering diseases: A French national study.

To the Editor: The COVID-19 pandemic was a concern for patients with autoimmune blistering diseases (AIBD), with an increased risk of COVID-19 in patients receiving rituximab, and a mortality rate observed in patients hospitalized for COVID-19 during the first COVID-19 wave in France of 38%.1Joly P. Incidence and severity of COVID-19 in patients with autoimmune blistering skin diseases: a nationwide study.J Am Acad Dermatol. 2022; 86: 494-497https://doi.org/10.1016/j.jaad.2021.10.034Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar The first vaccines were available in France from December 2020.2Mascellino M.T. Di Timoteo F. De Angelis M. Oliva A. Overview of the main anti-SARS-CoV-2 vaccines: mechanism of action, efficacy and safety.Infect Drug Resist. 2021; 14: 3459-3476https://doi.org/10.2147/IDR.S315727Crossref PubMed Scopus (135) Google Scholar Nevertheless, safety and efficacy of anti-COVID-19 vaccination are poorly known in AIBD population. Anti-COVID-19 vaccination may trigger AIBD flares and onset,3Damiani G. Pacifico A. Pelloni F. Iorizzo M. The first dose of COVID-19 vaccine may trigger pemphigus and bullous pemphigoid flares: is the second dose therefore contraindicated?.J Eur Acad Dermatol Venereol. 2021; 35: e645-e647https://doi.org/10.1111/jdv.17472Crossref PubMed Scopus (59) Google Scholar,4Pauluzzi M. Stinco G. Errichetti E. Bullous pemphigoid in a young male after COVID-19 mRNA vaccine: a report and brief literature review.J Eur Acad Dermatol Venereol. 2022; 36: e257-e259https://doi.org/10.1111/jdv.17891Crossref PubMed Scopus (13) Google Scholar and low vaccine immunogenicity was demonstrated in immunocompromised patients (hematological malignancies and organ transplantation).5Galmiche S. Luong Nguyen L.B. Tartour E. et al.Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review.Clin Microbiol Infect. 2022; 28: 163-177https://doi.org/10.1016/j.cmi.2021.09.036Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar We aimed to assess risk of AIBD flares (tolerance) and of COVID-19 after vaccination (efficacy). We conducted a French national retrospective study, from May to September 2021 (tolerance; 325 patients) and from October 2021 to March 2022 (efficacy; 244 patients). These time windows allowed: (1) full vaccination; (2) sufficient time of COVID-19 exposure after vaccination (efficacy). For the tolerance study, patients with AIBD previously diagnosed and receiving ≥1 anti-COVID-19 vaccine dose, with an 8-weeks minimal follow-up, were included. Patients with de novo AIBD or AIBD-flare confounding factors (ie, concurrent discontinuation of AIBD treatment) were excluded. For the efficacy study, patients should have received: (1) if immunocompetent, ≥2 vaccine doses or 1 dose in case of COVID-19 history; (2) if immunocompromised, ≥2 vaccine doses; with a 6-month minimal follow-up after the first dose. Patients were considered immunocompromised if receiving oral corticosteroids ≥10 mg/d, mycophenolate mofetil, cyclophosphamide, and azathioprine during the first vaccine dose, or rituximab during the 18 months before the first vaccine dose (Supplementary Material, available via Mendeley at https://data.mendeley.com/datasets/ss5xy6j3jy/1). Before anti-COVID-19 vaccination, most patients were in clinical remission (61%) or minimal clinical activity (24%) (Table I and Supplementary Table I, available via Mendeley at https://data.mendeley.com/datasets/ss5xy6j3jy/1). Most patients had a 2-dose vaccination schedule (83%), with BNT162b2 (Comirnaty) (82%). After a mean of 3.5 months after vaccination, 30/325 (9.2%) patients experienced AIBD flares. Twenty-five patients received an additional dose during follow-up (missing data: 5): only 2 (8%) had a new relapse. Flares were moderate (mean Bullous Pemphigoid Disease Area Index [BPDAI] 2.4 before vs 12.7 after vaccination), and controlled by topical corticosteroids in 80% of cases in BP (Supplementary Table II, available via Mendeley at https://data.mendeley.com/datasets/ss5xy6j3jy/1). On univariate analysis, the only factor associated with AIBD flares was baseline treatment with cyclines (P = .015) (Supplementary Table III, available via Mendeley at https://data.mendeley.com/datasets/ss5xy6j3jy/1).Table ICharacteristics of the studied population and autoimmune blistering disease subgroups (tolerance study)Data recordedTotal, N = 325 n (%)BP, N = 115 n (%)MMP, N = 107 n (%)PV, N = 66 n (%)PF, N = 19 n (%)EBA, N = 11 n (%)LABD, N = 5 n (%)DH, N = 1 n (%)PNP, N = 1 n (%)Sex (women)164 (51)48 (42)60 (56)42 (64)5 (26)6 (55)3 (60)00Age, y (mean ± SD)71.6 ± 14.678.4 ± 10.474.6 ± 11.060.7 ± 15.456.9 ± 17.762.1 ± 14.675.4 ± 13.55578Clinical activity of AIBD before vaccination Remission198 (61)77 (67)54 (50)47 (71)11 (58)7 (64)2 (40)00 Minimal activity79 (24)28 (24)28 (26)15 (23)5 (26)1 (9)01 (100)1 (100) Moderate activity41 (13)9 (8)21 (20)4 (6)1 (5)3 (27)3 (60)00 High activity7 (2)1 (1)4 (4)02 (11)0000AIBD under treatment at first vaccination∗Several treatments could be associated.284 (87)101 (88)95 (89)52 (79)18 (95)11 (100)5 (100)1 (100)1 (100) Rituximab†During the 18 months before the first anti-COVID-19 vaccine dose.88 (27)4 (3)24 (22)39 (59)14 (74)4 (36)2 (40)01 (100) Superpotent topical corticosteroids85 (26)54 (47)16 (15)9 (14)4 (21)1 (9)1 (20)00 Dapsone81 (25)6 (5)62 (58)01 (5)9 (82)2 (40)1 (100)0 Methotrexate37 (12)34 (30)3 (3)000000 Oral corticosteroids35 (11)9 (8)4 (4)15 (23)4 (21)02 (40)01 (100) Cyclines24 (7)9 (8)15 (14)000000 Omalizumab16 (5)14 (12)2 (2)000000 Conventional immunosuppressants‡Including mycophenolate mofetil, azathioprine, or cyclophosphamide.15 (5)6 (5)4 (4)4 (6)1 (5)0000AIBD flare after vaccination30 (9)15 (13)7 (7)4 (6)3 (16)1 (9)000 After first vaccine dose13 (4)6 (5)4 (4)1 (2)2 (11)0––– After second vaccine dose14 (4)9 (8)3 (3)1 (2)1 (5)0––– After third vaccine dose3 (1)002 (3)01 (9)–––AIBD, Autoimmune bullous skin disease; BP, bullous pemphigoid; DH, dermatitis herpetiformis; EBA, epidermolysis bullosa acquisita; LABD, linear IgA bullous dermatosis; MMP, mucous membrane pemphigoid; PF, pemphigus foliaceus; PNP, paraneoplastic pemphigus; PV, pemphigus vulgaris.∗ Several treatments could be associated.† During the 18 months before the first anti-COVID-19 vaccine dose.‡ Including mycophenolate mofetil, azathioprine, or cyclophosphamide. Open table in a new tab AIBD, Autoimmune bullous skin disease; BP, bullous pemphigoid; DH, dermatitis herpetiformis; EBA, epidermolysis bullosa acquisita; LABD, linear IgA bullous dermatosis; MMP, mucous membrane pemphigoid; PF, pemphigus foliaceus; PNP, paraneoplastic pemphigus; PV, pemphigus vulgaris. When evaluated for vaccination efficacy, with a mean of 10 months after vaccination, most patients had received a 3-dose vaccination schedule (73%), with BNT162b2 (Comirnaty) (80%) (Table II and Supplementary Table IV, available via Mendeley at https://data.mendeley.com/datasets/ss5xy6j3jy/1). COVID-19 occurred in 18/244 (7.4%) patients, including 3 (1.2%) with severe forms requiring hospitalization and 1 (0.4%) death (Delta variant). During the 3 postvaccination months, 20/26 (77%) immunocompetent patients, 19/31 (61%) drug-immunosuppressed patients, and 15/26 (58%) patients receiving rituximab exhibited protective levels of antispike antibodies (Supplementary Fig 1, available via Mendeley at https://data.mendeley.com/datasets/ss5xy6j3jy/1). Factors associated with COVID-19 were COVID-19 before vaccination (P = .003), immunosuppression (P < .001), rituximab therapy (P = .002), receiving <3 vaccine doses (P = .01), and nonprotective level of postvaccination antispike antibodies (P < .001) (Supplementary Table V, available via Mendeley at https://data.mendeley.com/datasets/ss5xy6j3jy/1).Table IICharacteristics of the studied population and autoimmune bullous skin disease subgroups (efficacy study)Data recordedTotal, N = 244 n (%)BP, N = 83 n (%)MMP, N = 82 n (%)PV, N = 57 n (%)PF, N = 11 n (%)EBA, N = 7 n (%)LABD, N = 3 n (%)PNP, N = 1 n (%)Sex (women)120 (49)35 (42)44 (54)35 (61)1 (9)3 (43)2 (66)0Age, y (mean ± SD)72.2 ± 14.779.0 ± 10.675.5 ± 11.561.5 ± 15.457.9 ± 14.561.3 ± 16.473.0 ± 23.579Significant comorbidities188 (77)71 (86)53 (65)46 (81)10 (91)5 (71)2 (67)1 (100) Immunosuppression111 (45)28 (34)28 (34)41 (72)9 (82)3 (43)1 (33)1 (100)Drug-induced∗Defined as treatment with rituximab, oral corticosteroids ≥10 mg/d, mycophenolate mofetil, azathioprine, or cyclophosphamide.87 (36)13 (16)22 (27)40 (70)9 (82)2 (29)01 (100)Cancer or hematological malignancy28 (11)15 (18)7 (9)2 (4)1 (9)1 (14)1 (33)1 (100)Solid organ or hematopoietic stem cell transplantation1 (0.4)01 (1)00000 Type 1 or 2 diabetes58 (24)28 (34)19 (23)7 (12)1 (9)1 (14)1 (33)1 (100) Complicated hypertension53 (22)23 (28)22 (27)6 (11)01 (14)1 (33)0 Obesity33 (14)18 (22)8 (10)5 (9)2 (18)000 Heart failure23 (9)15 (18)5 (6)2 (4)001 (33)0 Chronic kidney disease23 (9)15 (18)4 (5)3 (5)1 (9)000 Chronic lung disease13 (5)7 (8)2 (2)2 (4)1 (9)1 (14)00 Postvaccination COVID-1918 (7)4 (5)†Including 1 severe form.7 (9)‡Including 2 severe forms, 1 of which resulted in the patient’s death.5 (9)1 (9)1 (14)00BP, Bullous pemphigoid; EBA, epidermolysis bullosa acquisita; LABD, linear IgA bullous dermatosis; MMP, mucous membrane pemphigoid; PF, pemphigus foliaceus; PNP, paraneoplastic pemphigus; PV, pemphigus vulgaris.∗ Defined as treatment with rituximab, oral corticosteroids ≥10 mg/d, mycophenolate mofetil, azathioprine, or cyclophosphamide.† Including 1 severe form.‡ Including 2 severe forms, 1 of which resulted in the patient’s death. Open table in a new tab BP, Bullous pemphigoid; EBA, epidermolysis bullosa acquisita; LABD, linear IgA bullous dermatosis; MMP, mucous membrane pemphigoid; PF, pemphigus foliaceus; PNP, paraneoplastic pemphigus; PV, pemphigus vulgaris. In conclusion, anti-COVID-19 vaccination in AIBD patients is associated with low rate of minor flares, and protective against severe COVID-19. Vaccination and antispike antibodies monitoring are highly recommended in this population. None disclosed.