Efficacy of GM-CSF as an adjuvant to hepatitis B vaccination in patients with chronic renal failure--results of a prospective, randomized trial.
BACKGROUND
Chronic renal failure patients on hemodialysis are at an increased risk of acquiring hepatitis B infection. Hence vaccination against hepatitis B assumes great importance in these patients. However, the response to hepatitis B vaccination is poor, even when 4 double doses (40 microg) of the vaccine are given. This study was conducted to determine the efficacy of GM-CSF as an adjuvant to hepatitis B vaccine in CRF patients.


METHODS
CRF patients including both hemodialysis (HD) and non-dialysis (ND) patients were randomized to receive either placebo or a single injection of GM-CSF (in varying doses of 50 microg, 100 microg, 150 microg) a day prior to the 1st dose of recombinant hepatitis B vaccine (40 microg). Three more doses of the vaccine were given at 1, 2, and 6 months. The anti-HBs antibody titres were measured by ELISA at 3 and 7 months. Patients having antibody titres less than 10 IU/L were considered non-responders. The response rate and mean antibody titers were compared between the control (I) and GM-CSF (II) groups.


RESULTS
In group I, 31 and 27 patients were available for evaluation at 3 and 7 months respectively. In group II, 33 and 28 patients could be evaluated at the same time points. Within the control group (group I), the response rate in hemodialysis patients (63.6%) was lower as compared to non-dialysis patients (81.2%). The response rate in group II was higher than that in group I at both 3 months as well as 7 months (78.1% vs. 62.3% and 89.3% vs. 74.1%, p = ns). The best response rates in group II were observed when GM-CSF was used in a dose of 150 microg (90.9% at 3 months and 100% at 7 months). The mean antibody titers were also found to be higher in the group II as compared to group I (409.6 vs. 243.9 IU/L, p = 0.01).


CONCLUSIONS
The results of this randomized, prospective study suggest that: 1. Patients with chronic renal failure should be vaccinated for hepatitis B as chronic renal insufficiency is established. 2. GM-CSF is an effective adjuvant to hepatitis B vaccine in these patients especially when a priming dose of 150 microg is used prior to 1st dose of hepatitis B vaccination.
Nephrology Division, Department of Medicine, Maulana Azad Medical College, Lok Nayak Hospital, New Delhi, India. nanu_singh@yahoo.com
N P
NP
Singh
S K
SK
Mandal
A
A
Thakur
D
D
Kapoor
S
S
Anuradha
A
A
Prakash
R
R
Kohli
S K
SK
Agarwal
D000328:Adult; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000627:therapeutic use*; D006509:Hepatitis B / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D006435:Renal Dialysis; D012307:Risk Factors; D013997:Time Factors
D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor