Herpes zoster vaccination in inflammatory bowel disease: Evidence, guidelines, and reality

Table 1 Epidemiology of herpes zoster in inflammatory bowel disease and general population - herpes zoster in inflammatory bowel disease vs healthy population[3,5,6,10,11,12,14]

Parameter	General	IBD
Incidence/1000 PY	3.4 to 4.82	7.0 to 18.3
Relative risk		1.3-fold to 2.0-fold higher
Lifetime risk	25% to 30%	High-risk thresholds reached much earlier
Age-specific risk	Risk rises with age	Higher relative risk than age-matched healthy controls
Gender distribution	1.3 times higher incidence in females	Higher incidence in females

PY: Patient-years; IBD: Inflammatory bowel disease.

Table 2 Epidemiology of herpes zoster in inflammatory bowel disease and general population - herpes zoster in inflammatory bowel disease[10,11,14,16,17,20]

Feature	CD	UC
Overall incidence rate	Higher overall burden (15.9 cases per 1000 PY)	Slightly lower burden (13.6 cases per 1000 PY)
Relative risk (vs non-IBD)	1.66 times to 1.99 times	1.34 to 1.50
Risk in young adults	Dramatic risk increases with an IRR of 3.35 compared to healthy peers	Displays a lower relative risk increase than CD in this age group, with an aIRR of 1.85
Complication risk	High risk for disseminated or visceral disease when heavily immunosuppressed	High risk for complications, though crude incidence rates are generally lower than in CD

IBD: Inflammatory bowel disease; CD: Crohn’s disease; PY: Patient-years; IRR: Incidence rate ratio; UC: Ulcerative colitis; aIRR: Adjusted incidence rate ratio.

Table 3 Risk profile of drugs used in inflammatory bowel disease[18,21]

No risk	Low risk	High risk	Highest risk
Aminosalicylates	Vedolizumab	Corticosteroids	Tofacitinib (10 mg)
Budesonide	Ustekinumab	Azathioprine	Upadacitinib
		6-mercaptopurine	Anti-TNF + TP
		Infliximab	3 drug regimens
		Adalimumab
		Tofacitinib (5 mg)

TNF: Tumor necrosis factor; TP: Thiopurines.

Table 4 Adjusted odds ratio for herpes zoster in inflammatory bowel disease by therapy and disease type

Drug	IBD	UC	CD
Aminosalicylates[11,14,21] (baseline reference)	1.0	1.0	1.0
Budesonide[16]	1.0	1.0	1.0
Systemic steroids[11,21,21] (dose dependent)	1.7–2.0	1.6-1.9	1.8-2.1
Thiopurines[10,11,21,22,31]	1.8-2.2	1.6-2.0	2.0-2.4
Anti-TNF monotherapy[17,31]	1.5-1.8	1.4-1.7	1.6-1.9
Anti-TNF and thiopurine[17,31] (synergistic effect)	3.0-3.5	2.6-3.2	3.3-4.0
Vedolizumab[26,27]	0.9-1.1	0.9-1.0	1.0-1.1
Tofacitinib (5 mg)[25,26]	2.5-3.0	2.5-3.5	2.0-3.0
Tofacitinib (10 mg)[26,27] (highest risk in UC)	3.5-4.5	4.5-6.5	3.0-4.0
Other JAK inhibitors[26,27] (data from RA trials)	3.0-5.0	3.5-6.0	2.5-4.5

TNF: Tumor necrosis factor; UC: Ulcerative colitis; JAK: Janus kinase; RA: Rheumatoid arthritis; IBD: Inflammatory bowel disease; CD: Crohn’s disease.

Table 5 Differences between live attenuated zoster vaccine and recombinant zoster vaccine

Aspect	LZV (e.g., Zostavax)	RZV (e.g., Shingrix)	Ref.
Composition	Weakened live varicella-zoster virus (Oka/Merck strain) at high titer	Recombinant glycoprotein E antigen + AS01B adjuvant (MPL and QS-21)	[14,15,34,35]
Mechanism	Stimulates immunity via replication of attenuated virus	Boosts humoral and cell-mediated immunity without viral replication	[14,15,34]
Administration	Single subcutaneous injection	Two intramuscular injections, 2-6 months apart	[14,34,37]
Efficacy in general population	Approximately 51% against HZ in ≥ 60 years; approximately 67% against PHN; wanes to 20%-30% after 8-10 years	97% against HZ in ≥ 50 years; 91% in ≥ 70 years; > 90% against PHN; sustained for 7-10+ years	[15,34,35]
Efficacy in IBD/immunocompromised	Limited data; not recommended due to risks; approximately 50%-60% in non-IS but inferior long-term	65%-90% against HZ; 68%-90% in broader IS groups; reduces complications like PHN by 75%-89%	[35,37-39]
Safety	Generally safe in immunocompetent; mild local reactions common	Mild-moderate reactogenicity (pain, fatigue); no increased IBD flares (RR = 0.80)	[34,37,40]
Safety in immunosuppressed	Contraindicated; risk of dissemination and vaccine-strain infection	Safe; robust immunogenicity even on anti-TNF or vedolizumab; no flare risk	[14,15,34,35,40]
Contraindications	Immunosuppression (e.g., high-dose steroids, biologics, JAKi); pregnancy; history of anaphylaxis to gelatin/neomycin	History of anaphylaxis to components; acute febrile illness (delay until resolved)	[14,15,34,41]
Availability/preference	Phasing out; still used in some low-resource settings for immunocompetent	Preferred globally; widely available in United States/Europe; private/costly in India/Asia	[14,15,34,36]

IBD: Inflammatory bowel disease; HZ: Herpes zoster; PHN: Post-herpetic neuralgia; IS: Immunosuppressed; LZV: Live attenuated zoster vaccine; JAKi: Janus kinase inhabits; RZV: Recombinant zoster vaccine; AS01B: Adjuvant system 01B; MPL: 3-O-desacyl-4’-monophosphoryl lipid A; QS-21: Quillaja saponaria Molina fraction 21; RR: Relative risk; TNF: Tumor necrosis factor.

Table 6 Key studies on recombinant zoster vaccine in inflammatory bowel disease - efficacy against herpes zoster and complications

Ref.	Study	Population	Sample size	Key findings on HZ/complications	Vaccine effectiveness/HR/OR (95%CI)	Complications
Desai et al[39], 2024	Propensity-matched United States cohort	Adults ≥ 50 years with IBD (UC/CD)	5489 vaccinated (2 doses) vs 5265 unvaccinated (after PSM: Approximately 4774 per group)	Lower HZ incidence post-RZV; reduced short-term HZ risk. No significant difference in severe complications or PHN among those with HZ	aOR = 0.44 (0.32-0.62) for HZ; incidence 109 vs 24.2 per 1000 PY	Prevention-focused; no major difference in PHN/severe HZ post-onset
Tseng et al[37], 2025	Kaiser Permanente matched cohort	Adults ≥ 50 years with IBD	872 (2-dose vaccinated) vs 2550 unvaccinated (VE cohort); 1199 in SCCS for flares	Adjusted VE 65.1% against HZ; no increased IBD flare risk	VE 65.1% (24.8%-83.8%) against HZ	Supports HZ prevention (implying lower complications); no flare increase [RR = 0.80 (0.47-1.35)]
Wang et al[38], 2025	TriNetX real-world matched analysis	Adults with IBD (mixed ages, primarily adults)	1260 vaccinated vs 1260 unvaccinated (after matching from n = 12086)	Significantly lower HZ complications (PHN, CNS); no CNS cases in vaccinated. Stronger in UC, females, non-immunosuppressed	HR = 0.75 (0.58-0.97) for HZ complications; HR = 0.66 for PHN; uncomplicated HZ HR = 0.31 (0.26-0.37)	Direct complication reduction: PHN 5.8% vs 12.5%; CNS 0% vs 0.8%; ocular/disseminated similar
Caldera et al[40], 2025	Prospective immunogenicity/safety	Adults with IBD on vedolizumab or anti-TNF	67 patients (33 enrolled: 16 vedolizumab, 17 anti-TNF)	Robust immunogenicity (sustained antibodies/CMI); no IBD flares; mild AEs	N/A (immunogenicity focus); strong responses through day 425	Low flare rate (1.5%); indirect benefit via HZ avoidance
Khan et al[42], 2022	ZOE-HSCT and broader immunocompromised (IBD overlap)	Immunocompromised adults ≥ 18 years (e.g., post-HSCT, hematologic; proxy for immunosuppressed IBD)	Varies (approximately 1800 in pivotal trials)	VE approximately 68% against HZ; high against PHN (approximately 89%). Lower NNV for complications in high-risk groups	VE 68.2% (55.6%-77.5%) against HZ; 89.3% against PHN	Proxy data; reduced PHN/hospitalization; comparable across ages

HSCT: Hematopoietic stem cell transplantation; IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’s disease; PSM: Propensity score matching; VE: Vaccine effectiveness; SCCS: Self-controlled case series; TNF: Tumor necrosis factor; HZ: Herpes zoster; RZV: Recombinant zoster vaccine; PHN: Post-herpetic neuralgia; CNS: Central nervous system; CMI: Cell-mediated immunity; AE: Adverse event; NNV: Number needed to vaccinate; HR: Hazard ratio; OR: Odds ratio; CI: Confidence interval; aOR: Adjusted odds ratio; PY: Patient-years; N/A: Not applicable; RR: Relative risk.

Table 7 Indications for use of different types of herpes zoster vaccines in various guidelines

Guideline	Indications for LZV (live attenuated)	Indications for RZV (recombinant)	Ref.
ACG 2025 (United States)	Not recommended for IBD patients; contraindicated in those on immune-modifying therapy or aged < 50 if immunosuppressed	All IBD patients ≥ 50 years; ≥ 19 years on or planning immune-modifying therapy (e.g., JAKi, TNFi, high-dose steroids); regardless of prior HZ or varicella status	[41]
ECCO 2021 and 2025 (Europe)	Contraindicated in immunosuppressed IBD; limited to immunocompetent adults ≥ 50-60 years without IBD risks	Strong recommendation for all adult IBD on immunosuppression (≥ 18-19 years); treatment-tailored, prioritize JAKi users due to dose-dependent HZ risk; all ≥ 50 years	[23,52]
Indian Consensus Guidelines 2024 (general)	Not preferred	≥ 50 years universally; recommended in patients with immune compromising conditions including HIV	[53]
Asian (e.g., Korean, AOCD 2023-2025)	Contraindicated in immunosuppressed; optional for immunocompetent ≥ 50 in low-access settings	≥ 50 years in all; ≥ 19 years on JAKi or other IS; emphasize in high-HZ-burden populations (e.g., 10-12/1000 PY in IBD)	[14,15,54]
ACIP 2022 (United States, general with IBD overlap)	Contraindicated in immunocompromised; for immunocompetent ≥ 50-60 years	≥ 19 years if immunocompromised (including IBD on IS); ≥ 50 years universally	[35]

ACG: American College of Gastroenterology; ECCO: European Crohn’s and Colitis Organization; AOCD: Asian Organization for Crohn’s and Colitis; ACIP: Advisory Committee on Immunization Practices; LZV: Live attenuated zoster vaccine; IBD: Inflammatory bowel disease; RZV: Recombinant zoster vaccine; JAKi: Janus kinase inhabits; TNFi: Tumor necrosis factor inhabits; HZ: Herpes zoster; HIV: Human immunodeficiency virus; IS: Immunosuppressed; PY: Patient-years.

Table 8 Vaccination strategy for herpes zoster prevention in inflammatory bowel disease patients

Aspect	Recommendation	Ref.
Who	(1) All IBD patients ≥ 50 years; and (2) IBD patients ≥ 19 years on JAK inhibitors, TNF inhibitors, or high-dose corticosteroids (> 20 mg/day prednisone equivalent for ≥ 14 days)	[14,15,23,35,41,52,54]
When	(1) At diagnosis or during remission; (2) Before starting immunosuppression if possible; (3) During stable immunosuppression for RZV; and (4) Avoid LZV if immunosuppressed
How	(1) RZV: Two doses/ 0.5 mL each, 2-6 months apart, intramuscular; (2) LZV: Single dose (contraindicated in immunosuppressed); and (3) No routine boosters; revaccinate if incomplete series
Monitoring	(1) Assess for flares post-vaccination (low risk); and (2) Serologic testing not required pre-vaccination

IBD: Inflammatory bowel disease; JAK: Janus kinase; TNF: Tumor necrosis factor; RZV: Recombinant zoster vaccine; LZV: Live attenuated zoster vaccine.