What is the interaction between Influenza (flu) vaccine and Leflunomide (an immunosuppressive disease-modifying antirheumatic drug)?

From the Guidelines

Patients taking leflunomide can safely receive the annual influenza vaccination without interrupting their leflunomide dosing schedule. Leflunomide is a disease-modifying antirheumatic drug (DMARD) commonly used for rheumatoid arthritis and other autoimmune conditions, while the flu vaccine is an inactivated or recombinant vaccine that does not contain live virus. Although leflunomide suppresses the immune system to some degree, which theoretically could reduce vaccine effectiveness, the benefits of flu vaccination still outweigh any potential reduced response.

Key Considerations

• The provided evidence does not directly address the interaction between the flu vaccine and leflunomide 1.
• However, it discusses the administration of non-live attenuated vaccinations, such as the influenza vaccine, in patients with rheumatic and musculoskeletal diseases (RMD) who are taking immunosuppressive medications.
• For patients with RMD, giving non–live attenuated vaccinations is conditionally recommended regardless of patients’ disease activity, with a level of evidence rated as very low 1.
• It is generally recommended that immunocompromised patients, including those on immunosuppressive medications like leflunomide, prioritize getting vaccinated against influenza to prevent complications from infection.

Recommendations

• Patients should continue their regular leflunomide dosing schedule without interruption when receiving the flu vaccine.
• The timing of vaccination doesn't need to be coordinated with leflunomide dosing.
• If patients experience any unusual side effects after vaccination while on leflunomide, they should report these to their healthcare provider, though such occurrences are rare.

From the Research

Interaction Between Flu Vaccine and Leflunomide

• There is limited direct evidence on the interaction between flu vaccine and leflunomide.
• However, studies have investigated the immunogenicity and safety of influenza vaccines in patients with rheumatoid arthritis (RA) taking various disease-modifying antirheumatic drugs (DMARDs), including leflunomide 2.
• One study found that leflunomide was at least as effective as sulphasalazine and methotrexate, and equally well tolerated, in patients with RA 2.
• Another study compared the immunogenicity and safety of high-dose trivalent inactivated influenza vaccine (HD-TIV) and standard-dose quadrivalent influenza vaccine (SD-QIV) in patients with RA, including those taking leflunomide 3.
• The study found that patients who received HD-TIV were more likely to seroconvert than those who received SD-QIV, and that local and systemic adverse events were similar in both vaccine groups 3.
• Other studies have investigated the effect of rituximab and TNF-alpha blockers on the humoral response to influenza vaccination in patients with RA, but did not specifically examine the interaction between flu vaccine and leflunomide 4, 5, 6.
• Overall, while there is limited direct evidence on the interaction between flu vaccine and leflunomide, studies suggest that influenza vaccination is safe and effective in patients with RA taking various DMARDs, including leflunomide 2, 3, 4, 5, 6.

Immunogenicity and Safety of Influenza Vaccines in Patients with RA

• Studies have shown that patients with RA have a reduced response to influenza vaccination compared to healthy controls 3, 4, 5, 6.
• However, the use of high-dose influenza vaccines may improve the immunogenicity of the vaccine in patients with RA 3, 6.
• The safety of influenza vaccination in patients with RA has been demonstrated in several studies, with no increase in disease activity or adverse events reported 3, 4, 5, 6.
• Overall, the available evidence suggests that influenza vaccination is safe and effective in patients with RA, including those taking leflunomide and other DMARDs 2, 3, 4, 5, 6.

Disease-Modifying Antirheumatic Drugs and Influenza Vaccination

• Several studies have investigated the effect of DMARDs, including leflunomide, on the response to influenza vaccination in patients with RA 2, 3, 4, 5, 6.
• The available evidence suggests that DMARDs, including leflunomide, do not significantly affect the response to influenza vaccination in patients with RA 2, 3, 4, 5, 6.
• However, further studies are needed to fully understand the interaction between DMARDs and influenza vaccination in patients with RA 2, 3, 4, 5, 6.