The compromised immunologic status of patients with autoimmune inflammatory diseases, such as rheumatoid arthritis (RA) often exposes them to increased risk for infection and associated complications during the course of their disease, a risk that is associated with 1.5- to 2-fold higher risk for hospitalization and death from the complications of infection.1 The evidence linking immunosuppressive agents with increased infection risk is compelling. A systematic review that evaluated infection risk for the various biologic therapies that are now a standard of care for the treatment of RA, including abatacept, rituximab, tumor necrosis factor inhibitors, tocilizumab, and tofacitinib, show increased risk for infection associated with the majority of these agents.2 Furthermore, meta-analysis of 29 randomized controlled trials involving 11,879 patients, and specifically focused on tumor necrosis factor inhibitors, concluded that the risk for tuberculosis may be increased significantly in patients treated with this class of agents.3 Indeed the US Food and Drug Administration approval label for these agents includes a black box warning about the risk for infections, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections.

Vaccination can potentially prevent infections or can reduce the risk for infection significantly. Consequently, vaccinations in patients with RA are of crucial importance because of the increased risk for infections associated with the disease itself and with the immunomodulatory drugs used to treat it. Various institutions have published guidelines on vaccination recommendations for patients with rheumatologic disease. Specifically, the American College of Rheumatology provides vaccination recommendations for patients with RA who are starting or currently receiving disease-modifying antirheumatic drugs (DMARDs) or biologics4:

● pneumococcal,

● influenza,

● hepatitis B virus (HBV),

● human papilloma virus (HPV), and

● varicella-zoster virus.

The European League Against Rheumatism has published updated recommendations for the management of RA with synthetic and biologic DMARDs, which include recommendations for vaccination as well as a score to calculate the risk for infection in patients exposed to biologic DMARDs.5

The US Centers for Disease Control and Prevention (CDC) recommends annual influenza vaccine for adults with chronic diseases such as RA.6 Other important vaccines include pneumococcal vaccines, herpes zoster vaccines, as well as vaccines against HPV and HBV.1,6 Annual influenza vaccination saves lives. A study compared the risk for mortality between 3748 patients with RA who received annual influenza vaccine and 3748 matched control who did not receive the vaccination. The study found that patients who received influenza vaccine had reduced risk for hospitalization for septicemia, bacteremia, or viremia, and lower risk for mortality.7

Despite the elevated risk for infection and the CDC recommendation for annual influenza vaccination, the vaccination rate is low among patients with RA. A study presented at the 2018 American College of Rheumatology and Association of Rheumatology Health Professionals Annual Meeting in Chicago, Illinois, found that only 52.7% of those surveyed had ever received the influenza vaccination, and just 28.9% received the influenza vaccination in 2 consecutive years.8 In another study, just 54% of patients with RA on immunosuppressive medications were up to date with pneumococcal vaccination, and among new initiators of immunosuppressive medications, only 45% were vaccinated before starting immunosuppressive therapy.9

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Factors that contribute to the low vaccination rate among patients with RA have been explored, and the consensus is that the reasons are complex and multifactorial and possibly related to patient, physician, and system barriers. Available published studies have focused on interventions such as patient reminder and recall, including postcards, personalized phone calls, and home visits, with positive effect on improving vaccination rates among the target population.10,11 Missing from these studies is an exploration of physician and patient behavior change following interventions that can have an impact on vaccination acceptance and uptake rate among patients with RA. The systematic review by Vincent Gosselin Boucher, PhD, and colleagues attempted to address this gap by exploring change in provider prescription of vaccine preintervention and postintervention.12 Behavior change techniques identified in the studies evaluated included feedback and monitoring, pharmacologic support (ie, provided with vaccination documentation or advice to get vaccinated), and object triggers, such as paper reminders. Although only 5 articles of the 450 records reviewed met the study inclusion criteria, the study found that between preintervention and postintervention, vaccination rates for influenza, pneumococcal virus, and herpes zoster virus increased by a mean 16.6%.12 The authors acknowledge the low number of the included studies, the lack of randomized study design, and the heterogeneity of the study design, which precludes generalizability of the study findings. The study, however, initiates a dialogue on the potential value of interventions focused on changing patient and physician behavior to improve vaccination acceptance and uptake among patients with RA.

The findings from the systematic review by Gosselin Boucher et al may inform the design of additional studies to further explore interventions for behavior change. Motivational communication is a technique that involves training providers in evidence-based behavior change focused on shared decision making between the patient and the provider. Motivational communication has been shown to produce improvements in a wide range of health behaviors, including medication adherence, physical activity, and exercise, and was suggested by Gosselin Boucher et al as an intervention that can be explored to improve vaccination rates in patients with RA. Clearly, further studies are needed, with stakeholder involvement in study design. Studies to date suggest that a focus on behavior change may be the strategy to improve vaccination uptake in the at-risk population.

References

1. Meroni PL, Zavaglia D, Girmenia C. Vaccinations in adults with rheumatoid arthritis in an era of new disease-modifying anti-rheumatic drugs. Clin Exp Rheumatol. 2018;36(2):317-328.

2. Strand V, Ahadieh S, French J, et al. Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials. Arthritis Res Ther. 2015;17:362.

3. Zhang Z, Fan W, Yang G, et al. Risk of tuberculosis in patients treated with TNF-α antagonists: a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2017;7(3):e012567.

4. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26.

5. Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960-977.

6. US Centers for Disease Control and Prevention. Adults With Chronic Conditions: Get Vaccinated. Updated August 17, 2018. Accessed February 15, 2019.

7. Chen CM, Chen HJ, Chen WS, Lin CC, Hsu CC, Hsu YH. Clinical effectiveness of influenza vaccination in patients with rheumatoid arthritis. Int J Rheum Dis. 2018;21(6):1246-1253.

8. Coca A, Dolan J, Ritchlin CT. Rates of influenza vaccination in a cohort of patients with rheumatoid arthritis and psoriatic arthritis. Presented at 2018 ACR/ARHP Annual Meeting; October 19-24, 2018; Chicago, IL. Abstract 231.

9. Desai SP, Turchin A, Szent-Gyorgyi LE, et al. Routinely measuring and reporting pneumococcal vaccination among immunosuppressed rheumatology outpatients: the first step in improving quality. Rheumatology (Oxford). 2011;50(2):366-372.

10. Thomas RE, Lorenzetti DL. Interventions to increase influenza vaccination rates of those 60 years and older in the community. Cochrane Database Syst Rev. 2018;5:CD005188.

11. Jacobson Vann JC, Jacobson RM, Coyne-Beasley T, Asafu-Adjei JK, Szilagyi PG. Patient reminder and recall interventions to improve immunization rates. Cochrane Database Syst Rev. 2018;1:CD003941.

12. Gosselin Boucher V, Colmegna I, Gemme C, Labbe S, Pelaez S, Lavoie KL. Interventions to improve vaccine acceptance among rheumatoid arthritis patients: a systematic review [published online January 15, 2019]. Clin Rheumatol. doi: 10.1007/s10067-019-04430-7