Original article
HBV vaccination with Fendrix is effective and safe in pre-dialysis CKD population

https://doi.org/10.1016/j.clinre.2019.06.010Get rights and content

Highlights

  • The immunological response to hepatitis B virus vaccine in patients with chronic kidney disease is unsatisfactory due to the immune compromise from chronic uraemia.

  • A recombinant HB vaccine containing an adjuvant has been adopted (HBV-AS04) in order to improve the immune response in CKD population but the available evidence on this point is extremely limited.

  • The current evidence regards mostly patients on long-term dialysis who received HBV-AS04; we have conducted a prospective study (‘real-life’ practice) to assess immunogenicity and safety of HBV-AS04 in pre-dialysis CKD population.

  • The seroprotection (HBsAb > 10 mIU/mL) rate was 95% (97/102), according to per-protocol analysis; no major side effects were found.

  • It appears that HBV-AS04 is really an advance as it gives great seroprotection rates in CKD population.

  • We need studies provided with longer follow-ups to evaluate the immunological response in CKD patients after completion of HBV-AS04 vaccine course.

Summary

Background

Patients with chronic kidney disease have a poor response to hepatitis B vaccine due to the immunodeficiency conferred from chronic uremia. A recombinant HB vaccine containing an improved adjuvant system AS04 (HBV-AS04) has been manufactured but scarce evidence exists on HBV-AS04 use among patients with CKD.

Aim

To assess efficacy and safety of an adjuvanted recombinant vaccine (HBV-AS04) in a large cohort of CKD patients at pre-dialysis stage (with susceptibility to HBV infection).

Methods

Patients were prospectively enrolled to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 1, 2, 3, and 4. Anti-HBs surface antibody concentrations were tested at intervals of 1, 2, 3, 4, and 12 months. Multivariate analyses were performed to assess the parameters, which predicted immunologic response to HBV-AS04 vaccine.

Results

One hundred and seven patients were included and 102 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers  10 mIU/mL) was 95% (97/102) (mean anti-HBs antibody titers, 688.9 ± 385 mIU/mL), according to per-protocol analysis. Serum haemoglobin levels were greater in responder than non- or low-responder patients to HBV-AS04 (P = 0.04) and this was confirmed by multivariate analysis. The seroprotection rate at month 50 was 88% (30/34) with lower anti-HBs antibody titers (218.5 ± 269.6 mIU/mL, P = 0.001). No major side effects were observed.

Conclusions

Our prospective study performed in a real-world setting showed a high immunogenicity and safety of HBV-AS04 vaccine in patients with CKD not yet on maintenance dialysis. Studies provided with longer follow-ups are under way to assess the durability of seroprotection in responders.

Section snippets

Abbreviations

    AEs

    adverse events

    CAPD

    continuous ambulatory peritoneal dialysis

    CDC

    centers for disease control and prevention

    CI

    confidence intervals

    CKD

    chronic kidney disease

    CKD EPI

    Chronic Kidney Disease Epidemiology Collaboration

    eGFR

    estimated glomerular filtration rate

    ESRD

    end-stage renal disease

    GI

    gastrointestinal

    HBV

    hepatitis B virus

    HCV

    hepatitis C virus

    HIV

    human immunodeficiency virus

    HD

    haemodialysis

    IFN

    interferon

    PD

    peritoneal dialysis

    RT

    renal transplant

    STROBE

    Strengthening the Reporting of Observational studies in

Setting and study subjects

This was a prospective, cohort study in outpatients on regular follow-up at a metropolitan hospital (Milano city). There was a program-wide screening for hepatitis B virus infection susceptibility and immunization since early nineties at the unit. Hepatitis B virus susceptible patients with CKD were given an opportunity to participating in the study.

Inclusion criteria were receiving periodic follow-up at a inner city nephrology center, 18 years or older, serum HBsAg/anti-HBs negative at

Patient characteristics

We originally enrolled 107 patients, 102 of them completed the study, for which per-protocol analysis was done. Five patients did not complete the vaccine course – three patients were lost to follow-up, and two patients died or withdrew from the study on a voluntary basis, respectively.

The demographic, clinical and biochemical parameters of the patients at baseline are reported in Table 1. The majority of patients had Caucasian origin, none had detectable human immunodeficiency virus antibodies

Discussion

The evidence in the literature regarding the use of recombinant adjuvanted (HBV-AS04) vaccines in patients with CKD is extremely limited. In this prospective, cohort study aimed to assess immunogenicity and safety of HBV-AS04 in a large group of CKD patients not yet requiring dialysis we found a high immunization rate (97/102 = 95%); of note, this study concerns a real-life practice. As listed above, the study group presented several co-morbidities at baseline (such as arterial hypertension,

Conclusion

Our prospective cohort study conducted in a ‘real-life’ setting suggests a great immunogenicity and safety of HBV-AS04 among patients with CKD not requiring maintenance dialysis. Studies are under way to assess the persistence of anti-HBs antibodies in patients with CKD who have been subjected to active immunization successfully.

Disclosure of interest

The authors declare that they have no competing interest.

Acknowledgments

None.

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