Vaccinations in immunosuppressive-dependent pediatric inflammatory bowel disease

Table 1 Search strategies

Search terms	Search limitation	Number of search results
“inflammatory bowel disease” + “immunization”	Limited to human species and English language	436
“inflammatory bowel disease” + “vaccination”	Limited to human species and English language	284
“inflammatory bowel disease” + “pneumococcal”	Limited to human species and English language	44
“inflammatory bowel disease” + “Hepatitis B”	Limited to human species and English language	181
“inflammatory bowel disease” + “varicella”	Limited to human species and English language	68
“immunosuppression” + “pneumococcal”	Limited to human species and English language	191
“immunosuppression” + “Hepatitis B” + “vaccination”	Limited to human species and English language	141
“immunosuppression” + “varicella” + “vaccination”	Limited to human species and English language	71

Table 2 Studies of efficacy and safety of pneumococcal and hepatitis B vaccines in adult inflammatory bowel disease patients receiving immunosuppressive therapy

Ref.	Study design	Subjects (n.)	Comparison groups	Outcome measured	Adverse events	Effects
Andrade et al[38], 2015	Retrospective cohort	217	IBD patients treated with infliximab and/or azathioprine	Hepatitis B antibodies 1-3 mo after HepB series completion	No comment on adverse effects	Receipt of vaccination while under infliximab or azathioprine treatment resulted in decreased seroconversion (OR = 17.6, 95%CI: 8.5-33.9 and OR = 3.3, 95%CI: 1.6-9.1)
Cosio-Gil et al[39], 2015	Retrospective cohort	172	IBD patients	Hepatitis B antibodies 1-3 mo after HepB series completion	No comment on adverse effects	50.6% patients responded to 1st series (95%CI: 42.9-58.3) 66.8% patients responded to 1st or 2nd series (95%CI: 59.3-73.8) Older age associated with decreased response (for patients > 55 yr, OR = 3.6, 95%CI: 1.3-10.2)
Cekic et al[40], 2015	Retrospective cohort	125	IBD patients	Hepatitis B antibodies 1 mo after HepB series completion	No comment on adverse effects	Age over 45 years, active disease, CD subtype, and immune suppression negatively impacted vaccine response
Ben Musa et al[41], 2014	Retrospective, cross-sectional	500	IBD patients	Hepatitis B antibodies	No comment on adverse effects	Younger age associated with increased HepB vaccine response
Sempere et al[24] 2013	Retrospective cohort	105	IBD patients	Hepatitis B antibodies 1-3 mo after HepB series completion	No significant adverse events associated with vaccination	Ileal CD (P = 0.01), long-standing IBD (P = 0.03), low albumin (P = 0.02), and systemic steroid use with more than one dose (P = 0.02) associated with decreased response
Altunoz et al[42], 2012	Retrospective cohort	211-159 patients with IBD, 52 healthy controls	IBD patients and healthy controls	Hepatitis B antibodies at least 1 month after HepB series completion	No comment on adverse events	Diagnosis of IBD overall (P < 0.001), male sex among IBD patients (P = 0.01), immunosuppressive therapy (P < 0.001), and active disease (P < 0.001) associated with decreased response
Gisbert et al[19], 2012	Prospective cohort	241	IBD patients	Hepatitis B antibodies 1-3 mo after HepB series (accelerated schedule or double dose) completion	No direct comment on adverse events	Older age (OR = 0.96, 95%CI: 0.94-0.98, P < 0.001) and anti-TNF therapy (OR = 0.39, 95%CI: 0.20-0.76, P < 0.01) associated with decreased rate of seroconversion 65% of participants responded after the 1st or 2nd series
Kantsǿ et al[20], 2015	Randomized trial	157	CD patients receiving PCV13 vs PPV23	Specific antibody response to 12 pneumococcal serotypes 1 mo after vaccination	No significant adverse events related to vaccination	PCV13 induced higher post-immunization titers for 5 serotypes (P < 0.05), regardless of treatment Immunosuppressive treatment with or without anti-TNF-α impaired immune response to both vaccines
Lee et al[23], 2014	Prospective cohort	197	CD patients	Antibody response 1 mo after PPSV23	No serious adverse effects in study	Female gender and anti-TNF therapy (monotherapy or combination with immunomodulator) associated with decreased response
Fiorino et al[22], 2012	Prospective cohort	96	IBD patients	Antibody response 3 wk after PPSV23	No serious adverse effects in the study	Infliximab only and combination therapy associated with decreased response (P = 0.009 and P = 0.038, respectively)
Melmed et al[43], 2010	Prospective cohort	64-45 patients with IBD, 19 healthy controls	A) IBD patients not receiving immunosuppressive therapy B) IBD patients receiving immunosuppression C) Healthy controls	Specific antibody response to 5 pneumococcal serotypes 4 wk after PPSV23	No comments on adverse effects	Combination immunosuppression associated with decreased response rate (P ≤ 0.01)

CD: Crohn’s disease; HepB: Hepatitis B; IBD: Inflammatory bowel disease; PCV13: Pneumococcal conjugate vaccine; PPSV23: Pneumococcal polysaccharide vaccine; TNF: Tumor necrosis factor.

Table 3 Studies of efficacy and safety of pneumococcal and hepatitis B vaccines in pediatric inflammatory bowel disease patients receiving immunosuppressive therapy

Ref.	Study design	Subjects (n)	Comparison groups	Outcome measured	Adverse effects	Effects
Urganci et al[27], 2013	Prospective cohort	97-47 with IBD, 50 healthy controls	IBD patients and healthy controls	Hepatitis A and hepatitis B antibodies 1 month following hepatitis A vaccine and hepB series	No severe adverse reactions associated with vaccination	All participants seroconverted to hepatitis A IBD patients had decreased seroconversion to Hepatitis B (70.2% vs 90% in healthy controls, P = 0.02) No statistically significant association between treatment and vaccination response
Moses et al[27], 2012	Prospective, cross-sectional	100 IBD patients	IBD patients receiving infliximab	Hepatitis B immunity (anti-HBs ≥ 10 IU/mL)	No comments on adverse effects	Older age at diagnosis and study visit, pancolitis, and lower albumin levels associated with non-immunity (P < 0.05) Infliximab dose, duration, frequency did not affect baseline immunity; associated with decreased immunity to booster
Fallahi et al[44], 2014	Prospective cohort	38-18 with IBD; 20 healthy controls	A: IBD patients not receiving immunosuppressive therapy B: IBD patients receiving immunosuppression C: Healthy controls	Increase in total IgG 28 d after PPSV23 vaccination and percentage of switched memory B cells	No comments on adverse effects	IBD associated with decreased percentage of switched memory B cells and lower increase in total IgG level (P = 0.007 and P = 0.001, respectively)
Banaszkiewicz et al[29] , 2015	Prospective cohort	178-122 with IBD; 56 healthy controls	A: IBD patients not receiving immunosuppressive therapy B: IBD patients receiving immunosuppression C: Healthy controls	Specific antibody response 6-8 wk following 1 dose of PCV13	No serious adverse effects related to PCV13	Adequate vaccine response achieved in all participants (90.4% in IBD patients vs 96.5% in controls) with no significant difference between IBD patients and controls (P = 0.53) Immunosuppressive therapy associated with decreased rise in geometric mean titers (P = 0.04)

anti-HBs: Anti-hepatitis B surface antibody; CD: Crohn’s Disease; HepB: Hepatitis B; IBD: Inflammatory bowel disease; PCV13: Pneumococcal conjugate vaccine; PPSV23: Pneumococcal polysaccharide vaccine; TNF: Tumor necrosis factor.