Despite improved treatment for systemic vasculitis (SV) in recent decades, patients with the disease are still at increased risk for all-cause mortality. The mortality ratio among patients with antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis is 2.6 compared with healthy individuals. The most common cause of death in these cases in infection, which is also a significant cause of morbidity in vasculitis patients and is linked with the prolonged use of immunosuppressive therapy.
Immunosuppression is at its peak during the first year post-diagnosis, and previous findings show that a quarter of patients with SV had an infection episode during that time period. Additionally, SV patients were found to have a 5-fold risk of hospital admission for pneumonia as compared with age-matched healthy controls. While their risk of infection decreases over time, it remains higher than that of the healthy population.
To improve outcomes in this patient population, it is necessary to identify those with an elevated risk of treatment-associated side effects. It has been shown that cumulative immunosuppression, patient age, and extent of renal impairment are risk factors for infection and mortality.
“However, no immune biomarkers, beyond leucopenia… have been shown to help identify those with poor functional immune systems and increased risk of infection,” wrote the authors of a new study published in Arthritis Care & Research.
“Vaccination is not only therapeutic but also provides information on the health of the immune system,” they noted. Though the immune response to vaccination is often poor in immunosuppressed patients, it is recommended for infection prevention. The researchers investigated whether response to vaccination and a detailed examination of the immune system would predict infection risk and all-cause mortality in SV patients.
Patients at a vasculitis clinic were eligible for vaccination if they had been in stable remission for at least 6 months and met specific criteria regarding vaccine and medication history and other variables. Total immunoglobulin, antibody titers, and lymphocytes were measured in 92 SV patients before they received multiple vaccinations. Antibody titers were measured again 4 weeks and 2 years following vaccination, and infections and deaths were tracked.
According to results, the vaccinations were safely tolerated and were not associated with increased disease relapse. The overall rate of infection was 0.4 (interquartile range [IQR] 0.2–1.3) per patient per year, and 18 patients had died at a median of 2 years post-vaccination. Serum IgG levels and B cell counts predicted infection and vaccine response, while renal function, age, and vaccine response predicted all-cause mortality.
Summary & Clinical Applicability
“[Using the identified biomarkers] as risk stratification may allow identification of patients who may benefit from immunosuppression withdrawal if appropriate and/or the use of additional therapies, such as [intravenous immunoglobulin], as a way to reduce infection and mortality,” explained the authors.
Limitations & Disclosures
Because of the reduced immunosuppression used in patients in remission, the infection rates in the current study are lower than those in previous reports, and this “may explain the lack of association between vaccination response and infection,” the authors wrote.
In addition, they included meningitis vaccination in the study, which is not standard for this patient group but allowed them to assess T-cell dependent and T-cell independent vaccines. However, its inclusion “may limit the applicability of the vaccine response score,” they said.
Dr Richter disclosed consulting fees, speaking fees, and/or honoraria received from Pfizer, in the amount of less than $10,000. Dr Goldblatt disclosed consulting fees, speaking fees, and/or honoraria received from GlaxoSmithKline, Merck, Novartis, Pfizer, and Sanofi Pasteur, in the amount of less than $10,000 each.
David Morgan M, Richter A., Al-Ali S, Flint J, Yiannakis C, Drayson M, Goldblatt D, Harper L. Association of Low B Cell Count and IgG Levels With Infection, and Poor Vaccine Response With All-Cause Mortality in an Immunosuppressed Vasculitis Population. Arthritis Care Res. 2016; 68: 853–860. doi:10.1002/acr.22757.