Reduced COVID-19 vaccine response in patient treated with Dupilumab for IgG4 related disease

ABSTRACT

Case report Dupilumab is a novel anti-interleukin- 4 (IL-4) receptor-alpha monoclonal antibody that targets the signaling pathways of IL-4 and IL-13, which are key type 2 cytokines. Current evidence suggests that patients on dupilumab are not at significantly increased risk of SARS-CoV- 2 related hospitalization and mortality and clinicians should avoid preventive cessation of therapy in patients with moderate-to- severe disease necessitating systemic treatment with dupilumab. However, there has been limited data about adequate and durable humoral immune response after vaccination to SARS-CoV- 2 in these patients, with some recent evidence by Runnstrom et al. suggesting that patients with severe asthma or atopic dermatitis on biologic therapies have lower antibody levels after SARS-CoV- 2 mRNA vaccination compared to healthy adults. We previously reported the case of a 71-year- old man with IgG4 related-disease (IgG4-RD) that we successfully treated with dupilumab. This patient was followed over the past three-years while his IgG4-RD remained well controlled on dupilumab which he remained on during the pandemic. Based on the vaccination guidelines and availability, he received two SARS-CoV- 2 mRNA vaccinations on March 24, 2021 and June 18, 2021. On July 24, 2021 (36 days after his last vaccination), during his routine follow up assessment, he was found to have no antibodies against SARS-CoV2. In response to this, we facilitated for him to receive his third booster vaccination on November 10, 2021. In preparation for this, his dupilumab was held for 1 month prior to this date and was continued two weeks after the injection. On December 3, 2021 (23 days after), his SARS-CoV2 Spike Total AB was repeated and found to be elevated at 2282 while his SARS-CoV2 NPROT Total AB was negative, implying immune response through vaccination and not natural exposure. To our knowledge, this is the first case report on a patient with IgG4-RD controlled on dupilumab who was found to have adequate vaccine titres after his dupilumab was held for 1 month after failing to mount a response to the first two vaccination doses while on therapy. As there is evidence that lower vaccine-specific titers afford less protection against COVID-19, acknowledging that holding dupilumab may not be feasible in all cases, this report highlights this approach as one possible strategy to protecting these individuals who may unknowingly remain at high risk for severe disease.