Vaccine coverage, antibodies against measles, mumps, rubella, hepatitis B in inflammatory bowel disease and juvenile idiopathic arthritis children

Abstract

BACKGROUND

Children with juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD) face an elevated risk of severe infection owing to their diseases and the immunosuppressive treatment for disease control.

AIM

To compare scheduled vaccination coverage and the levels of post-vaccine antibodies against measles, mumps, rubella (MMR) and hepatitis B in pediatric patients with IBD and JIA.

METHODS

A comparative cohort study included 97 patients with IBD and 170 patients with JIA. Vaccination history was obtained from medical records, while post-vaccination immunity was assessed prospectively by measuring specific IgG antibody titers using enzyme-linked immunosorbent assays (Vector-Best JSC, Russia; IBL International, Germany) during routine visits between January 2022 and April 2023.

RESULTS

A complete two-dose MMR course had been administered to 66.3% of IBD patients and 55.9% of JIA patients (P = 0.121). By contrast, the three-dose hepatitis B schedule was completed in 74.2 % of IBD and 100 % of JIA patients (P < 0.001). Protective level of anti-vaccine antibodies against measles (47.7% vs 57.7%; P = 0.168); mumps (75.3% vs 80.0%; P = 0.366); rubella (74.4% vs 98.2%; P < 0.0001); and hepatitis B (44.8% vs 50.0%; P = 0.514) were detected in IBD and JIA patients, respectively.

CONCLUSION

Patients with IBD and JIA demonstrated different vaccination coverage patterns and levels of anti-vaccine antibodies. Routine baseline serology and timely booster vaccination should be implemented for all pediatric patients receiving chronic immunosuppression.

Key Words: Juvenile idiopathic arthritis; Inflammatory bowel disease; Vaccines; Measles; Mumps; Rubella; Hepatitis B; Anti-vaccine antibodies

Core Tip: Vaccination is the primary strategy for preventing infections in children. Patients with juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD) have reduced immunity and increased susceptibility to infections. The immunogenicity of vaccines in children with IBD and JIA remains a topic of controversy. The study compared vaccination coverage and antibody levels against measles, mumps, rubella, and hepatitis B in children with IBD and JIA. Patients with IBD demonstrated lower rates of seropositivity, particularly for rubella and hepatitis B. In contrast, patients with JIA tend to maintain a more stable response to vaccination.

INTRODUCTION

Vaccination is the principal strategy for preventing vaccine-preventable infections in childhood. Its implementation becomes markedly more complex when long-term immunosuppression is required, as in juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD).

Immunosuppressive therapy increases susceptibility to common pathogens and heightens the risk of severe outcomes; it may also attenuate vaccine immunogenicity[1]. Treatments such as tumor necrosis factor (TNF) inhibitors, high-dose glucocorticoids, and immunomodulators are effective in suppressing disease activity. However, they may impair immune function, thereby increasing susceptibility to vaccine-preventable infections[2].

Despite both diseases being immune-compromised, there are differences in the unique immunopathogenesis and treatment approaches between JIA and IBD, with a higher prevalence of biologics in pediatric rheumatology practice and more frequent use of corticosteroids and cytostatics in IBD patients. Also, IBD patients often have additional factors influenced by anti-vaccine antibodies, such as malnutrition, diarrhea, hepatic disease, and GI surgery.

The European Crohn's and Colitis Organisation (ECCO) and the European League Against Rheumatism therefore recommend accelerated and, where feasible, complete schedules of inactivated and live vaccines before treatment initiation or, when necessary, during ongoing therapy[3,4]. Despite these recommendations, vaccine uptake remains suboptimal—particularly among those treated with biologic agents—due to concerns about vaccine safety, potential disease flares, and reduced immunogenicity[5,6].

While numerous studies have confirmed the safety of vaccines in pediatric patients with immune-mediated conditions, including no significant increase in disease flares following immunization[3,4], the degree of vaccine-induced antibodies in this population remains a matter of debate. Some studies report adequate antibody responses, whereas others suggest diminished seroconversion rates, reduced antibody persistence, and lower efficacy in the context of ongoing immunosuppression[2,7,8].

Recent data suggest that specific immunosuppressive agents, including TNF inhibitors, high-dose glucocorticoids, and B-cell-depleting therapies, can negatively impact vaccine responses. A 2023 prospective cohort study showed that the effectiveness of the conjugated MenACWY vaccine against meningococcal infection in adolescents with JIA and IBD decreases with the use of anti-TNF therapy. It highlights the potential requirement for booster doses[7]. A systematic review of 31 studies further confirmed that patients on TNF inhibitors have impaired serologic responses to vaccines, such as hepatitis B and influenza[8].

The immunogenicity of the measles, mumps, rubella (MMR), and hepatitis B vaccines in patients with IBD and JIA has been evaluated in separate studies, with conflicting results. A cross-sectional study in IBD patients showed no significant difference in MMR antibody levels compared to healthy peers[9]. In contrast, a larger cohort of 437 IBD patients demonstrated significantly lower seropositivity, particularly among those with ulcerative colitis[10]. These discrepancies suggest variability in long-term vaccine-induced protection and highlight the importance of evaluating booster requirements[11]. A 2021 meta-analysis involving IBD patients found that only 39.7% achieved seroprotective levels following hepatitis B vaccination, with disease activity, older age, and combination immunosuppressive therapy identified as risk factors for poor response[12].

Despite substantial evidence on vaccine immunogenicity in either IBD or JIA cohorts, direct comparative studies between these two populations are lacking. Given differences in disease pathogenesis, immune dysregulation, and treatment strategies, it is plausible that vaccine responses may differ between these patient groups[3]. It is the first study to directly compare the anti-vaccine antibody levels between two diseases with some similarities in pathogenesis and treatment.

This study aims to compare vaccine coverage and post-vaccination antibody levels against MMR, and hepatitis B in children with IBD and JIA and to explore the potential impact of immunosuppressive therapy on serologic responses.

MATERIALS AND METHODS

Study design and population

This prospective cohort study included 97 pediatric patients with IBD and 170 pediatric patients with JIA. This cross-sectional analysis was conducted prospectively during routine clinical visits between January 2022 and April 2023. Blood samples for anti-vaccine antibody measurement were collected prospectively during the study period, while vaccination history was retrieved retrospectively from medical records.

Eligibility criteria

Inclusion criteria: Pediatric patients (aged 2–18 years) with a confirmed diagnosis of Crohn's disease, ulcerative colitis, or JIA who provided informed consent to participate. Availability of complete vaccination records and corresponding post-vaccination antibody data for MMR, and hepatitis B.

Exclusion criteria: Patients with missing vaccination data for MMR, or hepatitis B. Receipt of blood transfusions or intravenous immunoglobulin within the preceding six months due to potential interference with antibody titers.

Data collection and outcomes

Demographic information: Sex, age at disease onset, and age at study inclusion.

Clinical data: Type of IBD and JIA were assessed, and disease activity was evaluated using the Pediatric Crohn's Disease Activity Index (PCDAI) and the Pediatric Ulcerative Colitis Activity Index (PUCAI) at diagnosis and study inclusion. The IBD course was divided into three categories: Acute (< 6 months since the onset), chronic persistent (no remission episodes with a duration of more than 6 months during the relevant treatment), and chronic relapsed (remission lasting more than 6 months). For JIA: International League of Associations for Rheumatology classification subtype, disease duration, and treatment history.

Vaccination history: The type and timing of vaccinations, total number of doses received for measles, rubella, mumps, and hepatitis B, and compliance with the National Vaccination Schedule[13] were collected from patients who continued with scheduled vaccinations, particularly for MMR and hepatitis B. Additionally, disease course and treatment details were extracted from medical records.

Immunosuppressive therapy: Data on treatment regimens, including TNF-α inhibitors, immunomodulators (azathioprine, methotrexate, 6-mercaptopurine), and corticosteroids. Duration and intensity of immunosuppressive regimens.

Levels of anti-vaccine antibodies: IgG concentrations of anti-vaccine antibodies for measles, rubella, mumps, and hepatitis B were measured using enzyme-linked immunosorbent assay with commercially available kits from Vector-Best JSC (Russia) and IBL (Germany). The antibody levels were analyzed based on calibration curves generated with Dynex Technologies Inc. software (United States). Laboratory technicians performing antibody measurements were blinded to patient diagnosis and treatment group to minimize detection bias.

Protective antibody thresholds were established according to the manufacturer's guidelines: Measles: ≥ 0.18 IU/mL [coefficient of variation (CV): 8%; analytical sensitivity: 0.07–30 IU/mL]; rubella: ≥ 10 IU/mL (CV: 8%; analytical sensitivity: 2 IU/mL); hepatitis B (anti-HBs antibodies): ≥ 10 mIU/mL (CV: 8%; analytical sensitivity: 2 mIU/mL); mumps: Protective IgG level defined as positivity coefficient > 1.0.

Ethics

The study was approved by the Ethics Committee of St. Petersburg State Pediatric Medical University (protocol No. 09/02, dated November 2, 2022). The study adhered to the ethical principles of the Declaration of Helsinki, ensuring the protection of participants’ rights. All data were collected and processed anonymously.

Statistical analysis

All statistical analyses were performed using Statistica software (version 10.0, StatSoft Corporation, Tulsa, OK, United States). The Kolmogorov-Smirnov test was used to assess the normality of the quantitative data distribution. Missing data were excluded from the analysis. Descriptive statistics were reported as follows: Continuous variables: Median and interquartile range (Q1; Q3). Categorical variables: Absolute values and proportions. Comparative analysis: Pearson's χ² test or Fisher's exact test was used for categorical variables. The Mann-Whitney U test was used to compare continuous variables between two independent groups. A two-tailed P value of < 0.05 was considered statistically significant.

RESULTS

Patient demographics and disease characteristics

A total of 267 pediatric patients were included in the comparative analysis: 97 with IBD and 170 with JIA.

JIA cohort

The JIA group consisted of 170 patients, with a significantly higher proportion of females (67.7%) compared to the IBD group (46.4%, P < 0.001). The median age at study inclusion was lower in JIA patients [11.4 years; interquartile range (IQR): 7.6–14.8] compared to IBD patients (14.0 years; IQR: 11.0–16.0; P = 0.03). The age at disease onset was also significantly lower in the JIA cohort (6.0 years; IQR: 3.7–9.0) compared to the IBD cohort (11.0 years; IQR, 6.0–14.0; P = 0.01). The main JIA categories were systemic arthritis (n = 16, 9.4%), oligoarthritis (n = 73, 42.9%), polyarthritis (n = 61, 35.9%), and enthesitis-related arthritis (n = 20, 11.8%).

IBD cohort

Among IBD patients, 73 (75.0%) were diagnosed with Crohn’s disease and 24 (25.0%) with ulcerative colitis. Extraintestinal manifestations were observed in 15.3% of patients, including uveitis (4.2%), arthritis (2.1%), primary sclerosing cholangitis (7.4%), erythema nodosum (1.1%), and pyoderma gangrenosum (1.1%).

Disease activity decreased significantly from diagnosis to study inclusion: Median PCDAI score for Crohn's disease decreased from 37.0 (IQR: 25–45) to 15.0 (IQR: 0–30). The median PUCAI score for ulcerative colitis decreased from 35.0 (IQR: 33–45) to 2.5 (IQR: 0–10), indicating effective disease control at the time of inclusion.

Regarding the disease course, 10 patients (10.2%) had an acute course, 29 (29.6%) had chronic, persistent disease, and 58 (59.8%) had a chronic, relapsing course.

Systemic corticosteroids (greater than 1 mg/kg/day of prednisone equivalent) were used in 56 patients (60.1%) for a median duration of 2.0 months (interquartile range, 1.0–3.0 months). Conventional immunosuppressive therapy included azathioprine (65.3%), methotrexate (22.5%), 6-mercaptopurine (10.2%), and tacrolimus (2.0%). Topical anti-inflammatory therapy was used in 39 patients (39.8%).

Among the 76 patients who received at least one biologic agent, infliximab was used in 54 (70.6%), adalimumab in 23 (30.8%), and vedolizumab in 8 (10.3%); several patients received more than one biologic agent during their treatment course. The median duration of TNF-α inhibitor therapy was 3.5 months (interquartile range, IQR: 1.2–22.0). IBD-related surgical intervention was required in 12 patients (12.4%).

Immunosuppressive therapy and treatment modifications

Serologic testing was performed while patients were receiving their current immunosuppressive treatment regimens, with no pre-treatment baseline titers available for comparison. The median duration of therapy at the time of antibody measurement was 6 (3; 8) years for measles, mumps, and rubella and 11.0 (6.8; 13.3) for hepatitis B.

At the time of study inclusion, TNF-α inhibitors were more frequently used in IBD patients (51.8%) compared to those with JIA (33.0%, P < 0.0001). A high percentage of patients in both groups had received conventional non-biological immunosuppressive treatment at disease onset, with 83.5% in the IBD group and 90.6% in the JIA group (P = 0.09).

Therapeutic adjustments were as follows: 23.6% of IBD patients on biologics required dose escalation or interval shortening, and 13.2% needed a switch to another agent, compared with 9.4% in the JIA cohort. These figures illustrate the dynamic nature of treatment optimization in both diseases and will be considered when interpreting vaccine-immunity outcomes. Demographic characteristic is in Table 1.

Table 1 Demographic characteristics of patients with inflammatory bowel disease and juvenile idiopathic arthritis included in the study, n (%)/median (25^th-75^th percentiles).

Parameter	IBD (n = 97)	JIA (n = 170)	P value
Sex (females)	45 (46.4)	115 (67.7)	< 0.001
Age of the inclusion in the study	14.0 (11.0-16.2)	11.4 (7.6-14.8)	0.03
Age of the disease onset	11.0 (6.0-14.0)	6.0 (3.7-9.0)	0.01
Biological immunosuppressive treatment at study inclusion	88 (51.8)	32 (33.0)	< 0.0001
Immunosuppressive therapy at the time of the study	81 (83.5)	154 (90.6)	0.09

IBD: Inflammatory bowel disease; JIA: Juvenile idiopathic arthritis.

Comparison of vaccine coverage and levels of anti-vaccine antibodies between the studied groups

The proportion of children with protective levels of post-vaccine antibodies differed between the two cohorts (Table 2). Overall, children with IBD demonstrated lower levels of antibodies against all vaccines, with statistically significant gaps observed for mumps and rubella. The information for each vaccine is listed below.

Table 2 Post-vaccination immunity against measles, mumps, rubella, and hepatitis B in patients with inflammatory bowel disease and juvenile idiopathic arthritis, n (%)/median (25^th-75^th percentiles).

Parameter	IBD (n = 97)	JIA (n = 170)	P value
Antibodies against measles, IgG, GM, (IU/mL)	0.15 (0.0-0.35)	0.21 (0.04-0.53)	< 0.001
Complete vaccination against measles for age1	62 (63.9)	95 (55.9)	0.200
Patients with protective levels of antibodies against measles	41 (47.7)	98 (57.7)	0.016
Antibodies against mumps, IgG, GM, (IU/mL)	2.8 (0.9-5.0)	2.9 (1.3-5.3)	0.570
Complete vaccination against mumps for age1	69 (71.1)	95 (55.8)	0.014
Patients with protective levels of antibodies against mumps	73 (75.3)	96 (56.5)	0.003
Antibodies against rubella, IgG, GM	32 (0.0-52.0)	87.3 (45.3-198.3)	< 0.0001
Complete vaccination against rubella for age1	31 (32.0)	75 (44.1)	0.051
Patients with protective levels of antibodies against rubella	64 (74.4)	168 (98.2)	< 0.0001
Complete vaccination against hepatitis B for age1	78 (80.4)	163 (95.9)	0.00004
Patients with protective levels of antibodies against hepatitis B	39 (44.8)	85 (50.0)	0.432
Antibodies against hepatitis B, IgG, GM	0 (0-30)	9.3 (0.03-41.9)	0.024
Patients whose anti-vaccine antibody levels was detected before the treatment	4 (14.3)
Vaccine-associated adverse events anytime
No	85 (88.5)
Fever	4 (4.2)
Injection site reaction	6 (6.2)
IBD flare	1 (1.0)

¹According to the National vaccination schedule to the age.

IBD: Inflammatory bowel disease; JIA: Juvenile idiopathic arthritis.

Measles

Despite the similar rate of complete vaccination coverage between two cohorts (63.9% in IBD vs 55.9% in JIA; P = 0.200), JIA patients demonstrated higher geometric mean (GM) IgG levels (0.21 0.04-0.53 IU/mL) compared to IBD (0.15 0.0-0.35 IU/mL; P < 0.001), as well as the part of the patients with protective level (57.7% in JIA and 47.7% in IBD group; P = 0.016).

Mumps

In contrast, substantial differences were observed regarding the vaccination component against mumps. JIA patients had significantly lower levels of antibodies against vaccines (56.5%) compared to IBD patients (75.3%; P = 0.003), as well as a similar vaccination completeness rate (71.1% vs 55.8%; P = 0.014).

Rubella

The completeness of vaccination against the rubella was relatively higher in JIA patients (44%) compared to IBD (32%; P = 0.051) with higher IgG GM levels in JIA patients (87.3 IU/mL) compared to IBD (32.0 IU/mL; P < 0.0001) lead to higher proportion of JIA patients with positive antibodies (98.8%) than in IBD (74.4%, P < 0.0001).

Hepatitis B

Complete vaccination against hepatitis B was reported in practically all JIA patients, and only 80.4% of IBD patients met the age-appropriate immunization (P = 0.00004). The IgG GM levels of antibodies were higher in the JIA cohort (9.3 0.03-41.9 vs 0 0-30 IU/mL; P = 0.024) compared to in IBD patients, but the rate of patients with positive antibodies was equal (50% in JIA and 44.8% in IBD; P = 0.432). The data are presented in Figure 1 and Table 2.

Figure 1 The levels of antibodies against measles, mumps, rubella, and hepatitis B in children with inflammatory bowel diseases and juvenile idiopathic arthritis. A: Levels of antibodies against measles; B: Levels of antibodies against mumps; C: Levels of antibodies against rubella; D: Levels of antibodies against hepatitis B. IBD: Inflammatory bowel disease; JIA: Juvenile idiopathic arthritis.

DISCUSSION

This study presents a comparative analysis of vaccine coverage and post-vaccination immunity in pediatric patients with IBD and JIA, highlighting both shared challenges and disease-specific differences in maintaining protective antibody responses. These results indicate sub-optimal long-term humoral immunity in both diseases, with JIA patients retaining significantly better protection against rubella, while immunity to measles, mumps, and hepatitis B remains insufficient in both cohorts. The marked rubella gap may reflect differences in booster timing, age at diagnosis, or treatment-related modulation of immune memory.

Our data confirm that children with IBD have less complete vaccine-derived immunity than those with JIA, but the magnitude of the gap varies by the vaccine. The most significant and statistically robust difference concerned rubella: Protective IgG was present in 98.8% of JIA patients vs 74.4% of IBD patients (P < 0.0001). For mumps, the proportion of patients with positive antibodies was higher in the IBD cohort, but the difference was modest—75.3% vs 56.5% (P = 0.014). The observed differences could be explained by the younger onset age of JIA patients, a more extended period of exposure between the last specific vaccination and anti-vaccine antibody measurements, and a relatively longer treatment duration.

Our pediatric cohort revealed a greater loss of protective titers, specifically protective IgG for measles, which persisted in only 47.7% of children with IBD and 57.7% with JIA (P = 0.016). A prospective United States study by Cleveland et al[14] likewise showed that 13% of 122 adult IBD patients lacked detectable measles antibodies, and a further 3% had equivocal titers. Older age (≥ 50 years) and longer disease duration (≥ 10 years) were independent predictors of waning immunity[14]. Although the absolute proportions differ (adults generally receive an additional MMR booster in adolescence), both datasets converge on the same point: Documentation of a completed MMR schedule does not provide current measles protection once chronic immune dysregulation is present, so IBD patients have a higher risk of inadequate protective titers-particularly for rubella—echoing earlier reports of suboptimal vaccine-induced immunity in pediatric IBD cohorts[15].

Our study confirms that long-term humoral protection against hepatitis B in children receiving chronic immunosuppression is disappointingly low: Only 44.8% of patients with IBD and 50% of those with JIA, maintained anti-HBs levels ≥ 10 mIU/mL, despite documented completion of the primary three-dose schedule in 74.2% and 100% of cases, respectively.

These figures parallel—and only modestly exceed—the single-center experience of Watts et al[16], who found protective titers in 28% of 116 pediatric IBD patients without significant differences between subgroups of patients treated with corticosteroids, non-conventional or biological DMARDs. Taken together, both cohorts demonstrated that calendar compliance alone provides little assurance of durable hepatitis B immunity when immune-mediated disease and its treatment are involved. This finding aligns with earlier work suggesting that children with chronic inflammatory disorders often require booster doses to achieve or restore adequate hepatitis B immunity[17,18]. However, several surveys have reported higher overall vaccination rates in JIA than in IBD—an effect often attributed to greater vaccine advocacy among pediatric rheumatologists[19,20]. Our data show that calendar completion alone does not guarantee durable antibody protection.

On the other hand, our data sit below the pooled 61% (95%CI: 53–69) seroconversion rate reported in the meta-analysis by Jiang et al[17] for patients revaccinated against hepatitis B virus (HBV). Two factors likely explain this gap. First, Jiang et al's endpoint was the acute antibody response to a (re)-vaccination course, whereas we assessed the persistence of antibodies many years after infancy immunization[17]. Second, all children in our cohort had already received at least one immunosuppressive agent. In contrast, the meta-analysis revealed significantly higher response rates when vaccination was administered before such therapy [relative risk (RR) = 1.33 for immunomodulators and RR = 1.57 for anti-TNF-α agents].

Patients with JIA may have experienced more delays or hesitations related to vaccination after diagnosis. A notable observation was the relation between current TNF-α–inhibitor therapy and serological protection. In the pooled cohort, children receiving a biologic had higher odds of protective IgG against both measles (P = 0.004) and rubella (P = 0.0001), indicating that first-line TNF blockade does not diminish humoral immunity to these antigens and may even help maintain it. No significant association emerged for mumps (P = 0.81) or hepatitis B (P = 0.94), suggesting that determinants of positive titers for these vaccines lie outside simple TNF inhibition—potentially in booster timing, baseline antibody decay or concomitant methotrexate use. It should be noted, however, that children with at least three sequential biologic agents were over-represented in the rubella-non-protected subgroup (18.5% vs 0%; P = 0.002). Thus, while standard TNF-α inhibition does not appear to compromise vaccine-induced immunity[1,3,15], cumulative or intensified biological exposure may eventually erode long-term protection against rubella. Prospective studies that serially measure titers before and after biological switches are needed to clarify this dose-response effect.

Several studies have previously addressed vaccine immunogenicity in pediatric patients with IBD and JIA, yet the results remain conflicting. Some reports suggest that patients on immunosuppressive therapy can still mount adequate immune responses, while others indicate reduced levels of anti-vaccine antibodies compared to those of healthy individuals[10,15,17,20,21].

Our findings underscore the need for enhanced vaccination strategies in pediatric patients with IBD and JIA. Given the lower titers of anti-vaccine antibodies observed in IBD patients, clinicians should consider: Baseline serology and targeted boosters. All children with IBD or JIA should undergo baseline serological testing for the core childhood vaccines—MMR, hepatitis B, and, where available, diphtheria and tetanus—at the time of diagnosis and again before any significant escalation of immunosuppressive therapy. Patients with low anti-vaccine antibodies should prompt immediate booster vaccination, according to ECCO guidelines[1,3].

Periodic re-checks during long-term immunosuppression

Because biologics and conventional disease-modifying drugs may accelerate antibody waning, monitoring every 3 to 5 years is advisable, with shorter intervals for those receiving multiple biologic switches.

Integrated care pathways

Embedding vaccination checkpoints into gastroenterology and rheumatology follow-up visits—rather than relying solely on primary-care reminders—would help close the gap between real-life coverage and positive levels of antibodies against vaccines.

Periodic re-checks during long-term immunosuppression

Because biologics and conventional disease-modifying drugs may accelerate antibody waning, monitoring every 3 to 5 years is advisable, with shorter intervals recommended for individuals who receive multiple biologic switches.

Limitations

The primary limitation of this study is the relatively small sample size, which may affect the generalizability of the findings. Additionally, the study population exhibited high heterogeneity in terms of disease characteristics, treatment approaches, and the time elapsed since disease onset and study inclusion. Variations in the age of disease onset contributed to differences in vaccination coverage, with older patients being more likely to have missed scheduled vaccinations, which may have led to lower levels of anti-vaccine antibodies. These factors may have influenced the study outcomes and should be considered when interpreting the results. Differences in variables such as disease severity, time since vaccination, age at diagnosis, type and duration of immunosuppressive therapy, and time of antibody testing relative to treatment and cohort imbalance could skew the results. Although our data demonstrate lower rates of positive antibodies against vaccines in patients under immunosuppressive therapy, causality cannot be established due to the cross-sectional design and absence of pre-treatment antibody measurements. The observed differences may reflect treatment-related effects, underlying immune dysregulation, or a combination of both.

CONCLUSION

Despite apparently satisfactory documentation of primary immunization, real levels of anti-vaccine antibodies were found to be markedly lower. The most pronounced immunity gap occurred in IBD children for rubella and hepatitis B. Adherence to the national immunization schedule alone does not provide adequate immunological protection in children receiving chronic immunosuppression.

To minimize the "immunity window", the following measures should include baseline and periodic serological monitoring—prior to treatment initiation and every 3–5 years (or when therapy is escalated)—followed by targeted revaccination, accelerated booster administration of MMR and HBV immediately after diagnosis, especially in early-onset IBD and before initiation of combination immunosuppression and collaboration between specialists and primary physicians, including systematic reminders and incorporation of antibody checks into routine visits. Implementing regular seromonitoring and timely booster immunizations should become a cornerstone of strategies to prevent vaccine-preventable infections in this population.