Long-term immunogenicity and safety of the hepatitis B vaccine HepB-CpG (HEPLISAV-B) compared with HepB-Eng (Engerix-B) in adults with chronic kidney disease.

BACKGROUND: Hepatitis B virus (HBV) infection remains a significant global burden, especially for patients with chronic kidney disease (CKD) receiving hemodialysis. Three doses of HepB-CpG (HEPLISAV-B® vaccine) induced a superior immune response compared with 4 double doses of HepB-Eng (Engerix-B®) in a phase 3 trial (HBV-17) in adults with CKD. Here we report the long-term immunogenicity and safety of HepB-CpG and HepB-Eng in eligible participants of HBV-17 who enrolled in this optional 34-month follow-up trial (HBV-19). METHODS: HBV-19 is a multicenter, open-label, phase 3b trial of adults with CKD who previously received a complete series of HepB-CpG or HepB-Eng in the HBV-17 trial. Participants were assigned to seroprotection categories at enrollment on the basis of their antibody response to hepatitis B surface antigen (anti-HBs) in HBV-17. The objective was to evaluate the durability of seroprotection (defined as an anti-HBs concentration ≥ 10mIU/mL) induced by HepB-CpG and HepB-Eng. Participants whose anti-HBs concentration was below 10mIU/mL received additional HepB-CpG or HepB-Eng doses. RESULTS: 147 participants were enrolled; 66.7 % were men, median age was 65.0 years, and 83.7 % were white. The durability of seroprotection in participants with CKD was similar in those who received HepB-CpG and those who received HepB-Eng. Antibody concentrations ≥ 100mIU/mL persisted for longer in HepB-CpG than HepB-Eng recipients, among those with anti-HBs ≥ 100mIU/mL post vaccination. The geometric mean anti-HBs concentration in the HepB-CpG group was significantly higher than in the HepB-Eng group over time (P ≤ 0.0001). The safety profiles were similar between the vaccine groups. CONCLUSIONS: Due to the higher antibody levels induced by HepB-CpG in participants with CKD, seroprotection against HBV may be expected to persist longer than that induced by HepB-Eng. CLINICALTRIALS: gov: NCT01282762.

Immunogenicity and safety of a booster dose of the hepatitis B vaccine HepB-CpG (HEPLISAV-B®) compared with HepB-Eng (Engerix-B®) and HepB-AS04 (Fendrix®) in adults receiving hemodialysis who previously received hepatitis B vaccination and are not seroprotected: Results of a randomized, multicenter phase 3 study.

This study compared the immunogenicity and safety of a booster dose of HepB-CpG (HEPLISAV-B® vaccine) with HepB-Eng (Engerix-B®) and HepB-AS04 (Fendrix®) in patients receiving chronic hemodialysis. This was a multicenter, randomized, open-label, phase 3 study of adults receiving hemodialysis with antibodies to HBsAg (anti-HBs) <10 mIU/mL at study entry. The objective was to compare the seroprotection rate (SPR) induced by HepB-CpG with HepB-Eng or HepB-AS04. The SPR was defined as the percentage of patients with anti-HBs ≥10 mIU/mL post-vaccination. At 20 sites in Germany, 155 participants were randomized: HepB-CpG = 54; HepB-Eng = 50; and HepB-AS04 = 51. Of the 149 participants in the modified intention-to-treat population, 76.5% had not previously responded to at least one series of hepatitis B vaccine. Based on a post hoc analysis, the SPR in HepB-CpG recipients (52.8%; 95% confidence interval [CI]: 38.6%, 66.7%) was significantly higher than in HepB-Eng recipients (32.6%; 95% CI: 19.5%, 48.0%), and non-inferior to that in HepB-AS04 recipients (43.1%; 95% CI: 29.3%, 57.8%). Local post-injection reactions occurred in significantly fewer HepB-CpG (9.3%) than HepB-AS04 recipients (31.4%; p = .007) and at a similar rate to HepB-Eng recipients (8.2%). Systemic post-injection reactions in HepB-CpG recipients (18.5%) were similar to the HepB-AS04 group (19.6%) and higher than in the HepB-Eng group (12.2%). In this difficult-to-immunize population, a booster dose of HepB-CpG induced significantly higher levels of seroprotection than HepB-Eng with a similar safety profile. The higher levels of immunogenicity were not accompanied by higher levels of local post-injection reactions compared with HepB-AS04.

Online hemodiafiltration versus acetate-free biofiltration: a prospective crossover study.

Online hemodiafiltration (online HDF) and acetate-free biofiltration (AFB) are 2 innovative renal replacement therapies. Convincing evidence has shown that both techniques are superior to conventional hemodialysis in many aspects. The aim of the present investigation was to compare online HDF and AFB in 12 stable maintenance hemodialysis patients in a prospective, randomized crossover trial. Twelve stable dialysis patients, age 49.7 +/- 11.3 years and on dialysis for 83.5 +/- 76.7 months, were treated prospectively and randomly by either AFB, predilution HDF (pre-HDF), or postdilution HDF (post-HDF) for a total of 36 weeks using exclusively F60S high-flux dialyzers. Routine blood biochemical tests, bone metabolism parameters, and clearance for both small and larger molecular weight substances were measured at defined intervals. During the trial period inter- and intradialysis symptoms, e.g., hypotensive episodes and intradialysis arterial blood gas analyses, were recorded. Both online HDF and AFB were well accepted by the overwhelming majority of patients and also by the dialysis staff. Pretreatment sodium, total and ionized calcium, chloride, bicarbonate, and urea did not differ within or between the 3 treatment groups. Potassium increased slightly in HDF patients while phosphate and beta2-microglobulin (beta2-M) decreased in all groups. After dialysis, AFB patients exhibited a significantly higher bicarbonate concentration and lower potassium level when identical potassium concentrations in dialysate were used. Patients receiving AFB manifested less intradialysis partial pressure of oxygen drop and partial pressure of carbon dioxide rise than those on HDF treatments. HDF treatments could afford higher single-pool and double-pool Kt/V, higher effective urea and beta2M clearance, and lower total interdialysis symptom scores than the AFB treatment method. While bone metabolism parameters did not differ between the 3 dialysis modalities, some parameters such as deoxypyridinoline in HDF and osteocalcin, pyridinoline, and deoxypyridinoline in AFB deteriorated at the end of the crossover study. Aluminum concentration decreased progressively to about one-third of prestudy values at the end of the study with all 3 treatments. AFB was associated with a lower predialysis mean arterial pressure (MAP), a smaller drop in MAP during treatment, and similar hypotension episodes compared with the 2 HDF treatments. Albumin concentration showed a trend to decrease during the first 2 months of the trial period followed by a slight increase thereafter but still significantly lower than initial value at the end of crossover. Both online HDF and AFB share most of the features of optimal renal replacement therapy. Online HDF is superior to AFB in such aspects as increased delivered dialysis dose both for small and larger molecular weight toxins and less interdialysis symptoms. On the other hand, AFB is associated with a smaller effect on arterial blood gas values and improved intradialysis hemodynamic tolerance. Some dialysis-related symptoms and complications in the case of our AFB practice could be attributable, at least in part, to low dialysate calcium level.