Immunogenicity of Intradermal Versus Intramuscular BNT162b2 COVID-19 Booster Vaccine in Patients with Immune-Mediated Dermatologic Diseases: A Non-Inferiority Randomized Controlled Trial
Chutima Seree-aphinan,
Ploysyne Rattanakaemakorn,
Poonkiat Suchonwanit,
Kunlawat Thadanipon,
Yanisa Ratanapokasatit,
Tanat Yongpisarn,
Kumthorn Malathum,
Pornchai Simaroj,
Chavachol Setthaudom,
Onchuma Lohjai,
Somsak Tanrattanakorn,
Kumutnart Chanprapaph
Affiliations
Chutima Seree-aphinan
Department of Medicine, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Ploysyne Rattanakaemakorn
Department of Medicine, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Poonkiat Suchonwanit
Department of Medicine, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Kunlawat Thadanipon
Department of Medicine, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Yanisa Ratanapokasatit
Department of Medicine, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Tanat Yongpisarn
Department of Medicine, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Kumthorn Malathum
Department of Medicine, Division of Infectious Diseases, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Pornchai Simaroj
Department of Ophthalmology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Chavachol Setthaudom
Immunology Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Onchuma Lohjai
Immunology Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Somsak Tanrattanakorn
Department of Medicine, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Kumutnart Chanprapaph
Department of Medicine, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
The intradermal route has emerged as a dose-sparing alternative during the coronavirus disease 2019 (COVID-19) pandemic. Despite its efficacy in healthy populations, its immunogenicity has not been tested in immune-mediated dermatologic disease (IMDD) patients. This assessor-blinded, randomized-controlled, non-inferiority trial recruited patients with two representative IMDDs (i.e., psoriasis and autoimmune bullous diseases) to vaccinate with fractionated-dose intradermal (fID) or standard intramuscular (sIM) BNT162b2 vaccines as a fourth booster dose under block randomization stratified by age, sex, and their skin diseases. Post-vaccination SARS-CoV-2-specific IgG and interferon-γ responses measured 4 and 12 weeks post-intervention were serological surrogates used for demonstrating treatment effects. Mean differences in log-normalized outcome estimates were calculated with multivariable linear regression adjusting for their baseline values, systemic immunosuppressants used, and prior COVID-19 vaccination history. The non-inferiority margin was set for fID to retain >80% immunogenicity of sIM. With 109 participants included, 53 received fID (all entered an intention-to-treat analysis). The fID demonstrated non-inferiority to sIM in humoral (mean outcome estimates of sIM: 3.3, ΔfID-sIM [mean, 95%CI]: −0.1, −0.3 to 0.0) and cellular (mean outcome estimates of sIM: 3.2, ΔfID-sIM [mean, 95%CI]: 0.1, −0.2 to 0.3) immunogenicity outcomes. Two psoriasis patients from the fID arm (3.8%) developed injection-site Koebner’s phenomenon. Fewer fID recipients experienced post-vaccination fever (fID vs. sIM: 1.9% vs. 12.5%, p = 0.027). The overall incidence of disease flare-ups was low without a statistically significant difference between groups. The intradermal BNT162b2 vaccine is a viable booster option for IMDD patients troubled by post-vaccination fever; its role in mitigating the risk of flare-ups remains unclear.
