Rapid CommunicationInfluenza vaccine administration in rheumatoid arthritis patients under treatment with TNFα blockers: Safety and immunogenicity
Introduction
Patients with rheumatoid arthritis (RA) are at higher risk of infections than healthy people, due to the combined effect of their dysfunctional immune system and immunosuppressive therapy. The risk may approximately be calculated as double for infections which are mainly located at bone and joints, skin, soft tissues and respiratory level [1]. Moreover, infections may induce disease flare-up and be characterized by a severe clinical course, representing a frequent cause of death (20–55%) in immune-suppressed individuals [2]. These patients should be protected against infections by preventive vaccine administration, but a systematic application of such a practice has not been performed yet for the largely diffuse fear of inducing disease reactivation via the immune system stimulation [3]. Anecdotal studies [4], [5], more recently confirmed by a larger number of papers [6], [7], [8], [9], [10], have demonstrated the safety of preventive vaccinations in RA patients without highly active disease [11].
Among the vaccine-preventable respiratory diseases, influenza [10] and pneumococcal [12] infection have been more extensively studied, probably for their possible severity and the availability of safe and effective vaccines. In particular, influenza is highly incident (5–20% of the general population in epidemic periods) and may induce potentially severe complications [2]. A preliminary study on systemic lupus erythematosus (SLE) and RA patients, 2 of whom treated with tumor necrosis factor (TNF) α blockers, studied before and after influenza vaccination [11], could demonstrate vaccine safety, immunogenicity and efficacy. The regulatory T cells (Tregs), as identified by the contemporaneous CD4 and CD25 expression, were then also analyzed. Tregs, in fact, play a pivotal role not only in the maintenance of peripheral self-tolerance and prevention of autoimmune diseases, but also in the regulation of protective response to infections [13], [14].
The aim of this paper is to systematically study RA patients under treatment with TNFα blockers before and after influenza vaccination. Patients with a dysfunctional immune system, treated with TNFα blockers and stimulated by flu vaccination for 3 consecutive influenza seasons, represent an interesting model to analyze the immune system modulation [12], [15], [16]. Moreover, Tregs, as now identified, may be considered a further tool in order to explore immune system reaction to vaccine in subjects with immune-mediated inflammatory diseases under immunosuppressive treatment.
Section snippets
Study design
Twenty-eight RA patients, diagnosed on the basis of the American College of Rheumatology criteria [17], age range 33–67 years, 23 females, under treatment with TNFα blockers (Infliximab, Etanercept, Adalimumab), have been vaccinated, after informed consent, by intramuscular route with 0.5 trivalent non-adjuvanted split influenza vaccine (Vaxigrip, Sanofi Pasteur MSD, Lyon, France), at least once during three consecutive influenza seasons (2005–2006, 2006–2007 and 2007–2008), for a total amount
Safety
No significant increase of disease activity was found at T1 and T2 compared with baseline values in any season. Data shown are the mean of 3-year values, being representative of the behavior observed in each year (Table 1).
No severe (adverse reaction causing death or threatening survival or creating chronic infirmity) adverse reactions were observed in vaccinated patients and healthy controls. Mild systemic and local side effects are reported in Table 2. No significant difference could be
Discussion
The current study demonstrates that RA patients with low-moderate, stable disease, under treatment with TNFα blockers, vaccinated with a flu non-adjuvanted vaccine during three consecutive years, do not show any disease reactivation, as inferred by DAS, nor any ANA appearance/increase of titer as a consequence of vaccine administration, thus confirming its clinical and immunological safety [10], [11]. TNFα blockers, in fact, have been frequently described as ANA-inducing/increasing agents, with
Acknowledgments
The study was financially supported by the Sapienza University of Rome, grant 2005 (C26A059989) “Ricerca di Ateneo” and by the “Accordo di collaborazione tra Min.Salute/CCM e ISS/NIC: Costruzione ed implementazione di una rete di laboratori per la sorveglianza virologica dell'influenza, con particolare riferimento alla diagnostica dei virus influenzali con potenziale pandemico. Responsabile Scientifico: Dr.ssa Isabella Donatelli-FASC. 7M23.”
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2021, Journal of the American Academy of DermatologyCitation Excerpt :The majority of primary data on the safety and efficacy of vaccines in patients exposed to biologics focuses on tumor necrosis factor (TNF) alpha inhibitors (primarily infliximab and etanercept) and the anti-CD20 monoclonal antibody rituximab.74,76,77,79,80,83,96-145 Patients with rheumatoid arthritis and inflammatory bowel disease were the most frequently studied populations.76,77,83,97-101,103,105,108-110,113,114,116,117,120-122,124,126,127,129-131,133-137,139,140,142-146 No studies on the safety or efficacy of vaccination in patients exposed to the following biologics were identified: brodalumab, anakinra, omalizumab, guselkumab, risankizumab, or tildrakizumab (Table III).147-152