Do Encourage Your Scleroderma Patients at Risk to get Influenza Vaccine

Meliha C. Kapetanovic


Rheumatology. 2018;57(10):1691-1692. 

Vaccination is a cost-effective intervention to prevent infections. Influenza and pneumococcal vaccination is recommended for individuals at increased risk of these infections.[1,2] Patients with SSc receiving immunosuppressive treatment or those with predisposing conditions including interstitial lung disease belong to the target groups for these vaccinations. There are few studies that focus on the efficacy, antibody response and safety of the influenza vaccine in patients with SSc.[3,4] The current issue of Rheumatology publishes an important report by Sampaio-Barros et al.[5] from a case–control study investigating the impact of treatment, disease subtype and disease severity on the immunogenicity and tolerability of pandemic non-adjuvant influenza A, H1N1-like vaccine in patients with SSc.

SSc is an uncommon heterogeneous chronic CTD characterized by a complex interplay between autoimmunity, vasculopathy and fibrosis.[6] Based on skin involvement, SSc is classified into limited and diffuse disease, the latter usually being associated with more severe organ involvement.[6] Pulmonary involvement including interstitial lung disease and pulmonary arterial hypertension is a leading cause of increased morbidity and mortality in patients with SSc.[7,8] In the EULAR Scleroderma Trials and Research (EUSTAR) cohort, infections (including pneumonia) were reported as the most common non-disease-related cause of death.[8] Likewise, infections (mainly pneumonia) have been found to be a leading cause of death in a single-centre study in the UK.[9]

In spite of these facts, influenza vaccination coverage among SSc patients is still low.[10] Lack of recommendations from health-care providers and concerns regarding side effects is one of the leading causes of not being immunized. In addition, there is uncertainty whether SSc itself, e.g., the immunological disturbance as a part of the disease, or the treatment may influence the efficacy of the vaccine. Thus, there is need for better knowledge and higher levels of awareness regarding benefits of influenza vaccination among health-care providers. The important part is to provide evidence-based data supporting current recommendations.

Previously, a single dose of virosomal influenza vaccine in 46 SSc patients was shown to be safe, yielded satisfactory antibody response and was not associated with increased activity in SSc.[3] On the other hand, patients treated with immunosuppressants were not included. Another study including 26 SSc patients and 16 controls vaccinated with different influenza vaccines reported sufficient antibody response in SSc patients with the exception of a limited number of SSc patients with interstitial lung disease having lower response to H1N1.[4] In this rather small cohort of SSc patients, no safety issues were observed and the majority of disease activity factors were not affected.[4]

Dr Sampaio-Barros and colleagues now report results of a study on the immunogenicity and safety of the adjuvant-free pandemic influenza A (H1N1)-like vaccine in SSc patients.[5] Although being a single-centre study, this case–control study including 92 SSc patients with equal number age and gender matched controls is so far the largest vaccination study with this focus. The patient population reflects SSc patients with established disease likely to be encountered in an outpatient rheumatology practice. The majority of patients were women, and about two-thirds of the patients had limited SSc and had the expected autoantibody profile. In addition, ~50% were treated by the immunomodulating drugs. All patients fulfilled the 1980 ACR criteria for SSc and an additional validation of SSc diagnosis was performed by scrutinizing patients' medical charts. The immunogenicity was assessed by current immunological standards, that is, calculating seroprotection and seroconversion rates, geometric mean antibody titres and fold increase in geometric mean antibody titres.

A monovalent adjuvant-free influenza A vaccine comprising virus surface glycoproteins requires T cell-dependent antibody response. MTX and AZA can theoretically impair antibody response and have previously been shown to diminish vaccination response in patients with other rheumatic diseases.[2] However, Sampaio-Barros et al. demonstrated similar immunogenicity of a single dose of vaccine in patients and controls. Further analysis comparing patients with limited vs diffuse SSc and those with severe skin involvement vs mild/moderate involvement found comparable antibody responses. Immunomodulating treatment (MTX, AZA or steroids) did not affect the vaccine response.

Before vaccination, numerically higher proportions of patients with SSc had protective antibody levels (20.7%) compared with the controls (12%), probably due to previous exposure to influenza A antigen (previous infections, vaccination or cross-reactivity). However, the seroprotective rate increased to 87.3% of patients after vaccination, indicating satisfactory immunogenicity with over 60% of patients reaching protective antibody levels. Similar patterns were seen in SSc patients receiving DMARDs and controls.

The fold increase in antibody levels (calculated as post-vaccination antibody levels divided by pre-vaccinations levels) or seroconversion rate (the proportion of population with 4-fold increase of antibody levels) are more meaningful immunological parameters for estimating how immunomodulating remedies influence the ability of the immune system to respond to a vaccine challenge. Methotrexate treated patients in the study of Sampaio-Barros et al. had numerically lower seroconversion rate and fold increase compared with SSc without DMARDs but the difference was not statistically significant. The corresponding effect of AZA was less pronounced and SSc patients on this drug had even higher fold increase in geometric mean antibody titres compared with patients without immunomodulating treatment.

A strength of the study is a meticulous assessment of vaccine safety with diary cards distributed to all participants and consecutively collected at the end of follow-up providing the possibility to register side effects and the possible impact of SSc disease on the vaccine tolerability. Although being adjuvant-free, the vaccine was both sufficiently immunogenic and well tolerated. No case of increased activity or flare in SSc was reported and SSc clinical presentation did not influence the tolerability of the vaccine.

Taken together, data presented in the study by Sampaio-Barros et al. confirm that influenza vaccine using non-adjuvant pandemic influenza A vaccine is immunogenic in patients with SSc, including patients on traditional DMARDs such as MTX and AZA. The study provides further evidence for recommending influenza vaccination to patients with SSc.