Abstract

Patients with immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and inflammatory bowel disease, are at increased risk of infection. International guidelines recommend vaccination to limit this risk of infection, although live attenuated vaccines are contraindicated once immunosuppressive therapy has begun. Biologic therapies used to treat IMIDs target the immune system to stop chronic pathogenic process but may also attenuate the protective immune response to vaccines. Here, we review the current knowledge regarding vaccine responses in IMID patients receiving treatment with biologic therapies, with a focus on the interleukin (IL)-12/23 inhibitors. B cell-depleting therapies, such as rituximab, strongly impair vaccines immunogenicity, and tumor necrosis factor (TNF) inhibitors and the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) fusion protein abatacept are also associated with attenuated antibody responses, which are further diminished in patients taking concomitant immunosuppressants. On the other hand, integrin, IL-6, IL-12/23, IL-17, and B-cell activating factor (BAFF) inhibitors do not appear to affect the immune response to several vaccines evaluated. Importantly, treatment with biologic therapies in IMID patients is not associated with an increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or developing severe disease. However, the efficacy of SARS-CoV-2 vaccines on IMID patients may be reduced compared with healthy individuals. The impact of biologic therapies on the response to SARS-CoV-2 vaccines seems to replicate what has been described for other vaccines. SARS-CoV-2 vaccination appears to be safe and well tolerated in IMID patients. Attenuated but, in general, still protective responses to SARS-CoV-2 vaccination in the context of certain therapies warrant current recommendations for a third primary dose in IMID patients treated with immunosuppressive drugs.

Highlights

  • Immune-mediated inflammatory diseases (IMIDs) are a diverse group of clinically unrelated conditions, including, among others, rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PsO), and inflammatory bowel disease (IBD)

  • In a recent study evaluating the effectiveness of SARS-CoV-2 revaccination in IMID patients who failed to respond to two-dose mRNA vaccination, 80% of patients not previously exposed to rituximab achieved seroconversion after revaccination, whereas only 20% of those treated with B-cell depleting agents seroconverted [188]

  • Another study evaluating the efficacy of mRNA vaccines against infection in a Veterans Affairs cohort of 14,697 IBD patients in the US (20% were taking tumor necrosis factor (TNF) inhibitors) found that full vaccination status reduced the risk of infection by 69%, showing that the effectiveness of a two-dose course of an mRNA

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Summary

Introduction

Immune-mediated inflammatory diseases (IMIDs) are a diverse group of clinically unrelated conditions, including, among others, rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PsO), and inflammatory bowel disease (IBD) They share molecular mechanisms and are characterized by altered immune homeostasis that results in chronic excessive inflammation leading to tissue injury in affected organs and eventually functional disability [1]. It is likely that the vaccine’s ability to generate an effective immune response against SARS-CoV-2 will be affected by the type of medications patients are receiving The aim of this narrative review is to summarize current knowledge regarding vaccine responses in IMID patients treated with biologic therapies, with a focus on agents that inhibit interleukin (IL)-12 and/or -23, as various new IL-23 inhibitors are being approved for several IMID conditions

Increased Risk of Infections in Patients with IMIDs
Vaccines and IMIDs
Immune Response Necessary to Generate Immunity
Approved Biologic Therapies and Their Impact on Responses to Vaccines
Integrins
Co-Stimulators of T Cells
B Cells
Anti-TNF
Anti-IL-1
Anti-IL-17
Anti-IL-6
SARS-CoV-2 Vaccination in IMID Patients
Humoral Responses to SARS-CoV-2 in IMIDs
Cellular Responses to SARS-CoV-2 in IMIDs
Revaccination and New Variants
Vaccine Protection against SARS-CoV-2 Infection in IMIDs
Safety of SARS-CoV-2 Vaccines in IMIDs
Guidelines on SARS-CoV-2 Vaccination in IMIDs
Evidence Summary on SARS-CoV-2 Vaccination in IMIDs
Findings
Conclusions

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