COVID-19 vaccination and immunomodulatory or immunosuppressive drugs: indications and contraindications

Abstract

To the Editor, The COVID19 pandemic has taken millions of human lives and is still accelerating to severely affect globally. With the advent of SARSCoV2 vaccines viz, mRNA, recombinant adenovirus vector and whole virion inactivated vero cell, which are inactivated vaccines having emergency use authorisation granted by the US Food and Drug Administration on 11 December 2020, led to a ray of hope in the COVID19 pandemic. Immunotherapy has shown an importance in treating severe COVID19, but the development of vaccine has been considered to be crucial for protecting the uninfected. The Australasian medical dermatology group strongly recommended COVID19 vaccination in patients on immunomodulatory or biological agents as no specific contraindication or identifiable safety issues have been identified until. According to public health England’s immunisation against infectious disease, patients on immunosuppressed medications are extremely vulnerable and should be vaccinated. Patients who are on longterm immunosuppressive medications, such as methotrexate, cyclophosphamide, mycophenolate, systemic corticosteroids for more than a month and biological therapies such as antiTNF (Tumour necrosis factor) and antiCD20 monoclonal antibodies, may be considered as priority for vaccination. Systemic corticosteroids affect vaccine efficacy in a dosedependent manner. In a longitudinal study, it was found that >10 mg/day was associated with impaired humoral immunity. Rituximab and methotrexate have also been shown to reduce humoral response to seasonal influenza and pneumococcal vaccines. Druginduced B cell inhibition would not influence innate and CD8 T cell responses, which are central to SARSCoV2 elimination. The British Society of Rheumatology advised COVID19 vaccine course should be given 4 weeks or more prior to rituximab; moreover, suboptimal response is expected within 6 months of last rituximab infusion. Patients with rheumatoid arthritis, when vaccinated with influenza, hepatitis vaccines showed markedly blunting of seroconversion for 6–10 months after rituximab infusion. However, early data from case reports have suggested poor outcomes in patients with rituximabtreated COVID19. Such data are a red alert and reinforce the necessity of its judicious use for the most clinically crucial cases during this pandemic. Methotrexate cause humoral suppression by interaction with the B cell activation factor and increasing immunosuppressive adenosine and regulatory B cells. It has been seen that immunogenicity of influenza vaccine significantly improved by temporarily discontinuing methotrexate for 2 weeks postvaccination without causing an increase in rheumatoid arthritis disease activity. According to Public Health England’s immunisation against infectious disease, patients who are planned for immunosuppressive therapy, either methotrexate or cyclophosphamide, should ideally be vaccinated 2 weeks prior to their commencement. Azathioprine and mycophenolate mofetil have both shown to decrease the antibody titres after vaccination but not below the threshold seroprotection level; therefore, it is recommended to continue the treatment. AntiTNF agents have shown safety in context of live varicellazoster vaccine. It has been advised to continue these agents in vaccination drive as they also have been associated with a decrease in severity and hospitalisation of patients with COVID19. Tofacitinib also have been shown to be safe in context with varicellazoster vaccine. Discontinuation for 1 week before and after vaccination, yielded no effect in patients reaching serprotection. Available COVID19 vaccines are not contraindicated in patients on immunomodulatory or immunosuppressive agents, although it is indicated in most of the available