Systematic review of the efficacy and safety of intradermal versus intramuscular hepatitis B vaccination in end-stage renal disease population unresponsive to primary vaccination series

Figures & data

Figure 1. Literature search.

Table 1. Methodological quality of included studies.

Study	Randomization	Blinding	Concealment	Follow-up
Barraclough et al. (2009)	Adequate Computer generated permuted blocks of 4 without stratification, p. 96	Unclear Open-Label	Unclear	Adequate; 7 lost to follow-up 4 due to patient preference 1 due to transplantation and two because of death 5 ID, 2 IM
Radziszewski et al. (2007)	Unclear	Unclear	Unclear	Unclear
Micozkadioglu et al. (2007)	Unclear “Randomly assigned”, p. 286	Unclear	Unclear	Adequate 2 lost to follow-up from IM group. One exitus, another transferred to another HD center
Fabrizi et al. (1997)	Adequate Table of random numbers, p. 1205	Unclear	Unclear	Unclear

Table 2. Demographics of included studies.

	Barraclough et al. (2009)		Radziszewski et al. (2007)	Micozkadioglu et al. (2007)		Fabrizi et al. (1997)
	ID	IM	Combined patient data	ID	IM	ID	IM
Age (years)	60 ± 15	54 ± 18	56 (22–78)	60	55.5	67.4	63.1
Gender (M:F)	17:12	17:13	38:24	20:13		13:12	17:8
Body mass index (kg/m^2)	26 ± 7	27 ± 5	NA	23	23	NA	NA
Time on dialysis (months)	35 (22–48)	31 (15–70)	23 (1–118)	28	29.5	41	19
Diabetes	10	7	9.6%	NA	NA	8	5
HCV	NA	NA	7 patients HCV-Ab and HCV-RNA positive	NA	NA	28% (7/25)	12% (3/25)
Hemoglobin (g/L)	11.0 (8–12.1)	10.8 (9.8–12.0)	NA	10.1	9.9	NA	NA
Albumin (g/L)	3.8 (3.5–4.0)	4.0 (3.8–4.3)	NA	3.9	3.7	NA	NA
Kt/V	1.4 (1.3–1.7)	1.4 (1.3–1.5)	NA	1.2	1.2	NA	NA
ESA use	23	24	61	4000 IU/wk	4000 IU/wk	NA	NA
Etiology of ESRD
• Chronic GN	NA	NA	18%	13% (4 patients)		6/50 = 12%
• Diabetic nephropathy	NA	NA	14.5%	32% (10 patients)		13/50 = 26%
• Chronic interstitial nephritis	NA	NA	10.5%	13% (4 patients) Tubulointerstitial nephritis		5/50 = 10%
• Polycystic kidney disease	NA	NA	5%	NA	NA	8/50 = 16%
• Nephroangiosclerosis	NA	NA	NA	NA	NA	10/50 = 20%
• Kidney cancer	NA	NA	3.3%	NA	NA	NA	NA
• Amyloidosis	NA	NA	1.6%	6% (2 patients)		NA	NA
• Lupus nephritis	NA	NA	1.6%	NA	NA	NA	NA
• Autoimmune causes	NA	NA	NA	NA	NA	1/50 = 2%
• Unknown etiology	NA	NA	45%	19% (6 patients)		“Others” 7/50 = 16%

Note: NA indicates that data were not available.

Table 3. Results of included studies.

						Seroconversion (antibody >10 IU/L or ≥ 10 IU/L) n (ID%):n(IM%)
Reference	Primary vaccination	N (ID:IM)	Vaccine type	Intradermal and intramuscular injection dose	Cumulative dose ID:IM (mcg)	1 mo	2 mo	3 mo	6–9 mo	12 mo	20 mo
Barraclough et al. (2009)	40 mcg × 3 IM HBV vaccination and <10 IU/L antibody at 1 month	59 (29:30)	Engerix B (GlaxoSmith Kline Pharmaceuticals)	ID: 5 mcg twice/week for 8 weeks on dialysis days IM: 40 mcg at week 1 and 8 on non-dialysis days	80:80	NA	23(79):12(40) p = 0.002	NA	NA	NA	NA
Radziszewski et al. (2007)	40 mcg × 4 IM HBV vaccination and and <9 IU/L antibody in a period of 1–6 months	62 (49:13)	Engerix B (SmithKline & Beecham)	ID: 10 mcg every week for 12 weeks IM: 10 mcg every week for 12 weeks *Maximum of 2 booster 10 mg doses given if antibody <10 IU/L *If antibody >100 IU/L, further vaccination terminated	120:120 Reminder doses given to 15 patients. Study does not specify which patients were given the reminder doses, or how many doses were given	43(88):11(85)	42(86):13(100)	43(88):11(85)	41(84):12(92)	43(88):9(69)	NA
Micozkadioglu et al. (2007)	Unresponsive to 2 series of 40 mcg × 4 IM HBV vaccination	31 (17:14)	Genhevac B (Pasteur)	ID: 10 mcg every week for 8 weeks IM: 40 mcg at 0, 1, 2, and 6 months	80:160	NA	NA	NA	16(94):7(50) p = 0.011	NA	NA
Fabrizi et al. (1997)	40 mcg × 3 IM HBV vaccination	50 (25:25)	Engerix B (SmithKline & Beecham)	ID: 5 mcg every week for 16 weeks IM: 40 mcg at 0 and 1 month	80:80	24(96):10(40) p = 0.001	NA	21(83):11(44) NS	17(69):4(14) p = 0.048	13(50):0(0) NS	8(30):0(0) NS
Combined seroconversion rates						67(91):22(55) p = 0.0001	65(83):25(58) p = 0.0048	64(86):22(58) p = 0.0016	74(81):23(44) p < 0.0001	56(76):9(24) p < 0.0001	8(30):0(0) p = 0.0069

Appendix 1. Sixty-three of 113 Results from Embase, MEDLINE and Cochrane Cochrane Central Register of Controlled Trials Literature Search (50 duplicates not listed).

Article	Included	Excluded
Dhillon et al. (2012)		5
Resic et al. (2011)		1
Medeiros et al. (2011)		5,6
Wang et al. (2010)		3
Alavian et al. (2010)		6, 7, 8
Barraclough et al. (2009)	Yes
Medeiros et al. (2009)		3
Morais et al. (2007)		5
Sorkhi et al. (2006)		8
Karahocagil et al. (2006)		4, 8
Mat et al. (2006)		6, 7
Di Paolo et al. (2005)		5
Chau et al. (2004)		4, 6
Somboonsilp et al. (2003)		5
Kovacic et al. (2003)		1
Vlassopoulos (2003)		3
Choy et al. (2002)		5, 6
Anandh et al. (2000)		5, 6
Milkowski et al. (2000)		1
Charest et al. (2000)		4
Ghosh (2000)		3
Rault et al. (1995)		4,6
Poux et al. (1995)		1
Theilacker et al. (2014)		1, 4, 5, 6
Momeni et al. (2012)		7
Hassan et al. (2014)		6
Medeiros et al. (2011)		6
Fabrizi et al. (2011)		3
Momeni et al. (2011)		7
Wang et al. (2010)		6
Levin (2009)		6
Barraclough et al. (2009)		3
Micozkadioglu et al. (2007)	Yes
Radziszewski et al. (2007)	Yes
Gombos et al. (2006)		1, 3, 6
Chanchairujira et al. (2006)		4
Argani et al. (2006)		4, 6
Fabrizi et al. (2006)		3
Roozbeh et al. (2005)		4
Charest et al. (2003)		4, 6
Milkowski et al. (2000)		8
Charest et al. (2000)		4
Fabrizi et al. (2000)		3
Vlassopoulos et al. (1999)		6
Ozener et al. (1999)		4, 6
Rosman et al. (1999)		3
Propst et al. (1998)		4
Vincent et al. (1998)		6
Fabrizi et al. (1997)	Yes
Vlassopoulos et al. (1997)		5, 6
Terribile et al. (1996)		1, 4
Chang et al. (1996)		8
Mettang et al. (1996)		4
Sirsat et al. (1995)		6
Waite et al. (1995)		6, 7
Poux et al. (1995)		3, 6
Vlassopoulos et al. (1994)		6
Reid et al. (1994)		3
Suma et al. (1994)		6
Marangi et al. (1994)		3
Mettang et al. (1993)		3
Ono et al. (1991)		4
Van Geelen et al. (1987)		4, 5, 6