Immunogenicity and safety of an investigational AS02(v)-adjuvanted hepatitis B vaccine in patients with renal insufficiency who failed to respond or to maintain antibody levels after prior vaccination results of two open, randomized, comparative trials

An investigational AS02(v)-adjuvanted hepatitis B (HB-AS02) was compared with a licensed conventional recombinant hepatitis B vaccine (HBVAXPRO™; Sanofi Pasteur MSD, Lyon, France) in pre-dialysis, peritoneal dialysis and hemodialysis patients aged ≥18 years who had failed either to respond to prior vaccination with a conventional hepatitis B vaccine (Study A; n=251) or to maintain protective antibody concentrations after prior hepatitis B vaccination (Study B; n=181). These were open, randomized, comparative trials. Mean (range) age was 65.9 (31-92) and 64.6 (29-92) years in the two studies, respectively. In Study A, two doses of HB-AS02 given one month apart were found to be superior to two doses of the licensed vaccine in terms of seroprotection rate (76.9% versus 37.6%) and anti-HBs geometric mean antibody concentration (GMC; 139.3 versus 6.9mIU/ml), with antibody concentrations ≥100mIU/ml in 61.1% and 15.4% of subjects in the two groups, respectively. In Study B, one month after administration of a single booster dose, seroprotection rates were 89.0% in the HB-AS02 group and 90.8% in the licensed vaccine group, 81.3% and 60.9% of subjects had antibody concentrations ≥100mIU/ml, and anti-HBs GMCs were 1726.8 and 189.5mIU/ml. HB-AS02 was found to be more reactogenic than the licensed vaccine. In summary, the investigational HB-AS02 vaccine induced higher seroprotection rates and anti-HBs GMCs than a licensed conventional hepatitis B vaccine in uremic patients who had failed to respond or to maintain protective antibody titers after prior hepatitis B vaccination

Type of dialysis access at first dialysis session accordingly with different studied subgroups.

<p>Abbreviations: ER+P, early referral and planned patients; ER+NP, early referral and non-planned patients; LR+P, late referral and planned patients; LR+NP, late referral and non-planned patients. PD, peritoneal dialysis; HD, hemodialysis; AVF, arterio-venous fistula. Figure represents a diagram of bars showing the different types of accesses at first dialysis session. Accesses were as follows for the total population: 34.5% AVF, 8% peritoneal catheter, 8.5% temporal hemodialysis catheter and 49% permanent HD catheter. For ER+P: 77% AVF, 21% peritoneal catheter, no temporal hemodialysis catheter and 2% permanent HD catheter. For ER+NP: 0.8% AVF, 2.6% peritoneal catheter, 9% temporal hemodialysis catheter and 88% permanent HD catheter. For LR+P: 89% AVF, 8% peritoneal catheter, no temporal hemodialysis catheter and 3% permanent HD catheter. For LR+NP: 0.4% AVF, 1% peritoneal catheter, 18% temporal hemodialysis catheter and 80% a permanent HD catheter.</p

Patients Flowchart for clinical study evaluation.

<p>Abbreviations: ER, early referred patients; LR, late referred patients; P, planned dialysis start patients; NP, non-planned dialysis start patients; ER+P, early referral and planned patients; ER+NP, early referral and non-planned patients; LR+P, late referral and planned patients; LR+NP, late referral and non-planned patients. A total of 626 patients started dialysis in 2012 from 25 Integrated Care Setting Clinics in Poland, Hungary and Romania at Diaverum Renal Services but only 547 were evaluated after excluding patients returning from a previous kidney transplantation (n = 23) and from one center with incomplete data (n = 56). Evaluated patients were primarily divided into two groups according with type of referral being 281 patients ascribed to the early referral and 266 patients into the late referral. Both groups were secondarily divided into another two groups each, depending on type of dialysis start. 168 patients were considered as early referred and with a planned dialysis start, 113 patients were considered as early referred but with a non-planned dialysis start, 63 patients were considered late referred but with planned dialysis start and 203 patients were late referred and had non-planned dialysis start. Planned dialysis patients were 231 of the total population and non-planned dialysis start were 316.</p

Clinical characteristics according to planning of dialysis start.

<p>Clinical characteristics according to planning of dialysis start.</p

Reasons for non-planned start and need of urgent dialysis start.

<p>Reasons for non-planned start and need of urgent dialysis start.</p

Peritoneal dialysis (PD) incidence (%) according with different studied subgroups.

<p>Maximum PD incidence was observed in the optimal care treated patients group being 22%. PD ranged 18% in the planned dialysis start, 16% in the early referred patients, 12% at modality information provision, 6% in the non-planned dialysis start, 5% in the late referral and no PD was observed if never previously informed. PD at the first dialysis session occurred in 8% and as first chronic RRT in 11% of the total studied population.</p

Clinical characteristics according to initial RRT modality.

<p>Clinical characteristics according to initial RRT modality.</p

Multivariate logistic regression for planned versus non-planned dialysis start.

<p>Pseudo r2 = 0.26.</p

Characteristics of patients with early referral (>3months) to Integrated Care Settings clinics follow-up according to planning of dialysis start.

<p>Characteristics of patients with early referral (>3months) to Integrated Care Settings clinics follow-up according to planning of dialysis start.</p