Sage Journals: Discover world-class research

Abstract

Background:

Ulcerative colitis (UC) in pediatric patients often results in corticosteroid (CS) dependency, with many individuals developing resistance to conventional treatments such as anti-TNF agents. Vedolizumab, a monoclonal antibody targeting α4β7 integrin, has shown promise in adult populations, but data on its efficacy and safety in children and adolescents are limited.

Objectives:

This systematic review aims to assess the effectiveness and safety of vedolizumab in treating UC in pediatric patients.

Design, data sources, and methods:

The PRISMA statement’s guidelines were followed in conducting this systematic review. Up until December 2024, a thorough search was carried out using keywords associated with inflammatory bowel disease (IBD), vedolizumab, and pediatric populations in the Cochrane Library, EMBASE, and PubMed. Case series of children and adolescents (less than 18 years old) with UC or unclassified IBD who were treated with vedolizumab were included in the research. Data on clinical response, mucosal healing, corticosteroid-free remission, clinical remission, and adverse events were extracted. Descriptive statistics were used in the statistical analysis.

Results:

A total of 14 papers were considered in the current evaluation of the effectiveness and safety of vedolizumab. Nearly one-third (36%) of patients with UC/IBD-U experienced clinical remission at 6 weeks, half of the patients at 14 weeks (50%), and 48% and 53% of patients at 22 weeks, respectively. Forty-five percent of patients maintained clinical remission after 1 year. Less than 8% of UC/IBD-U patients experienced serious side effects, while 15%–34% of patients experienced mucosal healing.

Conclusion:

Vedolizumab exhibits promising efficacy and a favorable safety profile in treating pediatric UC, with a sizable portion of patients achieving both clinical and corticosteroid-free remission. However, due to the limited sample sizes and lack of investigations, more randomized controlled trials and long-term research are needed to confirm these findings and develop more reliable clinical guidelines for its use in children and adolescents with UC. This means that even if the initial findings are promising, additional and better testing is required to ensure that vedolizumab is both effective and safe for young patients with UC.

Trial registration:

The PROSPERO registration number for this systematic review is CRD420250651513.

Plain language summary

Vedolizumab for children and teenagers with ulcerative colitis: what the research shows

Ulcerative colitis (UC) is a long-term condition that causes inflammation in the large intestine, leading to symptoms such as diarrhea, abdominal pain, and fatigue. It can be especially challenging to treat in children and teenagers. Many young patients become dependent on steroid medications or stop responding to standard treatments over time. Vedolizumab is a newer type of medication known as a biologic. It works by targeting the inflammation specifically in the gut, rather than affecting the entire immune system. This focused action may help reduce side effects and improve treatment outcomes. Researchers reviewed 14 studies involving children and teens with UC or IBD-unclassified who were treated with Vedolizumab. Their goal was to understand how well the medicine worked and how safe it was for younger patients. The findings showed that about 1 in 3 children improved within the first 6 weeks of treatment. By week 14, almost half of the patients were experiencing better disease control, and around 45% maintained these improvements after one year. Endoscopic healing—when the gut lining looks healthier on a scope—was seen in 15% to 34% of patients. Serious side effects were uncommon, occurring in fewer than 8% of cases. These results suggest that Vedolizumab may be a safe and effective option for treating children and teenagers with UC, especially when other treatments are not working well. However, more large and long-term studies are needed to confirm how best to use this medicine in young people.

Keywords

inflammatory bowel diseases pediatric treatment ulcerative colitis vedolizumab

Introduction

Antibiotics, biologics, corticosteroids (CS), immunomodulators, probiotics, and aminosalicylates are typical medical treatments for inflammatory bowel disease (IBD), especially ulcerative colitis (UC).¹ The high rate of relapse associated with UC may lead to a dependence on or resistance to corticosteroids in many individuals. Young patients are more likely than adults to be dependent on steroids, with rates of 45% and 8%, respectively.² About 20%–40% of individuals may eventually lose their responsiveness throughout the years (a subsequent loss of responsiveness), even though other patients do not respond to the initial treatment (original no-response).^3–7 This highlights the ongoing need for innovative therapies that focus on several inflammatory pathways linked to the pathophysiology of UC.⁸ In addition, between 10% and 40% of individuals do not respond to anti-TNF drugs, although there has been significant advancement in IBD treatment.⁹

A new, completely humanized monoclonal antibody (IgG1) called vedolizumab targets the gut specifically. It prevents gut T cells from sticking to mucosal cellular adhesion molecule-1 by inhibiting α4β7 integrin. The GEMINI clinical studies have demonstrated the effectiveness and safety of vedolizumab in treating intermediate-to-serious Crohn’s disease (CD) or UC in adults.^10–12 In May 2014, the FDA approved, followed by approval from Europe.^13,14 Vedolizumab is advised by current guidelines for UC patients who are not responding to anti-TNF or steroid treatments.^15–17

In instances of chronic activity or steroid dependence following the failure of anti-TNF agents, the European Crohn’s and Colitis Organization and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition advocate for vedolizumab as a second-line biological therapy for UC in pediatric patients.¹⁸ Moreover, when the optimization of immunomodulators and anti-TNF medications fails to attain or sustain clinical remission, it is recommended for CD.¹⁹ There is currently insufficient data to support the use of vedolizumab in children, and it is off-label for this age range. Since the safety profile of vedolizumab cannot be presumed to be the same as that of adults, it needs to be independently demonstrated. This makes it essential to keep an eye on the medication’s safety at all times, particularly as its use among younger patients increases.²⁰ Therefore, reviewing the available evidence and assessing vedolizumab’s efficacy and safety in treating UC in children and adolescents is the main objective of the current study.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed in the conduct of this systematic review (Supplemental File 1), which was prospectively recorded in the PROSPERO database (Registration number: CRD420250651513).

The strategy of search

From the database’s creation until December 2024, a thorough literature search was conducted using the electronic databases PubMed, EMBASE, and The Cochrane Library. We also looked through the reference lists of the included articles and performed a focused Google Scholar search to increase the scope of coverage and reduce publication bias. Controlled vocabulary and free-text terms, such as “inflammatory bowel disease,” “vedolizumab,” “ulcerative colitis,” “child,” and “adolescent,” were combined in the search approach. The initial search was conducted without any limits on language or publication date. A full search strategy for each database is included in Supplemental File 2.

Eligibility criteria

Inclusion criteria

Studies were included if they met the following criteria: Involved pediatric or adolescent patients (<18 years) with IBD (including UC or unclassified IBD), or patients under pediatric care up to 21 years. Assessed treatment with vedolizumab. Published in English. Reported at least one of the predefined outcomes.

Exclusion criteria

Studies were excluded if they met any of the following: Non-human studies. Studies on adult patients (>21 years). Case series with fewer than five participants. Editorials, letters, or conference abstracts without full data. Duplicate publications or ongoing/incomplete studies.

Outcomes

Clinical response, clinical remission, corticosteroid-free clinical remission, mucosal healing, and vedolizumab safety—defined as adverse events (AEs) the original study authors believed were related to the medication—were the main outcomes assessed. These outcomes were chosen based on clinical relevance and consistency across included studies.

Data extraction and quality assurance

Two independent reviewers (K.A.H. and R.K.A.-F.) looked at full texts, abstracts, and titles using the predefined eligibility criteria. Disagreements were resolved through discussions or consultation with a third senior reviewer (A.A.H.). An effort was made to ensure data processing was transparent and reproducible. Data that were extracted included study characteristics (author, year, country, and study design). The kind of IBD, patient characteristics, vedolizumab dosage and treatment plan, and documented side effects and clinical outcomes.

Statistical analysis

We conducted a descriptive analysis on the extracted data, summarizing categorical results as percentages with 95% confidence intervals (CIs), and reporting continuous data as means with standard deviations (SD) if normally distributed, or medians with interquartile ranges otherwise. Because of the small sample sizes and variability among studies, a formal meta-analysis was not possible; thus, statistical judgments were made using recognized methods suitable for small study synthesis, with heterogeneity addressed qualitatively.

Results

Supplemental File 1 describes this search strategy. A total of 715 citations were gathered from PubMed, EMBASE, and the Cochrane Library. Of these, 14 studies were left for analysis after 701 studies had been excluded for various reasons.^21–34

Clinical remission rates were reported from 11 trials.^{21–24,28–34} Clinical response rates were reported in six investigations.^{22,24,28,29,32,34} Four research studies evaluated mucosal healing,^23,26,28,34 and seven studies looked at remission rates without CS.^{21–24,27,30,34} Without making a distinction based on condition, 13 studies provided safety results for UC/IBD-Unclassified combination.^{21–25,27–34}

Tables 1 and 2 summarize the study’s parameters, while Table 3 displays the patient demographics. Vedolizumab dosages, concurrent medications, patient age, sample size, duration of treatment, follow-up periods, and outcome criteria might all differ. Vedolizumab dosages ranged from 3.6 to 10.3 mg/kg, with the majority of patients receiving 300 mg.

Table 1.

Characteristics of included studies.

Study (author, year, country)	Singh et al. (2016)²¹USA	Conrad et al. (2016)²² USA	Ledder et al. (2017)²³ Multi-country	Schneider et al. (2018)²⁴Austria	Olbjørn et al. (2020)²⁵ Norway	Jossen et al. (2020)²⁶ USA	Dolinger et al. (2021)²⁷ USA	Fabiszewska et al. (2021)²⁸ Poland	Garcia-Romero et al. (2021)²⁹ Spain	Hajjat et al. (2021)³⁰ USA	Kakiuchi and Yoshiura (2022)³¹ Japan	Hyams et al. (2022)³²USA	Yokoyama et al. (2023)³³ Japan	Atia et al. (2024)³⁴ Six countries
Study design	Retrospective case series	Prospective case series	Retrospective case series	Retrospective case series	Case series	Retrospective case series	Prospective case series	Retrospective case series	Retrospective case series	Retrospective case series	Retrospective	RCT-phase II	Retrospective	Prospective
Outcome definitions
a. Corticosteroid-free clinical remission or clinical remission	Clinical remission: PUCAI < 10	Steroid-free remission: Inactive PUCAI (<10) and no current corticosteroid therapy	Steroid- and EEN-free remission: PUCAI <10 without the need for new medications or surgical intervention;	Clinical remission: PUCAI <10 points	Not reported	Corticosteroid-free clinical remission: partial Mayo score <2 and off corticosteroids	Corticosteroid-free remission: partial Mayo score <2, and no form of corticosteroids for at least 4 weeks	Clinical remission: PUCAI ⩽10 after induction phase (4th dose week) and maintenance phase (10th dose week)	Clinical remission: PUCAI <10	Corticosteroid-free clinical remission: PUCAI <10	Clinical remission: PUCAI <10	Reduction in complete Mayo score of ⩾3 points and ⩾30% reduction from baseline	Clinical remission: PUCAI ⩽10 after induction phase	Corticosteroids -free and EEN-free remission at 14 weeks
b. The criteria of response	Not reported	PUCAI decrease ⩾20	Not reported	Not reported	Not reported	Not reported	Not reported	PUCAI decrease ⩾20 after 4th dose week	PUCAI decrease ⩾20	Not reported	Not reported	PUCAI decrease ⩾ 20	Not reported	Not reported
c. Criteria of mucosal healing	Not reported	Not reported	UC endoscopic index of severity, =0 in UC/IBD unclassified	Not reported	Not reported	Histological remission: Nancy Index score ⩽1 in ulcerative disease	Not reported	The level of fecal calprotectin: a statistically significant decrease in l fecal calprotectin level between baseline and after vedolizumab commencement	Not reported	Not reported	Not reported	Not reported	Not reported	The level of fecal calprotectin: a statistically significant decrease in its level between baseline and after vedolizumab commencement

EEN, exclusive enteral nutrition; IBD, inflammatory bowel disease; PUCAI, pediatric ulcerative disease activity index; RCT, randomized controlled trials.

Table 2.

Medication histories for the included patients.

Study	VDZ dose	Proportion of patients anti-TNF experienced	Previous medications	Concomitant medications
Singh et al. (2016)²¹	300 mg (n = 39); 6 mg/kg (n = 11); 5 mg/kg (n = 2)	47/52	Infliximab, Adalimumab, certolizumab	Azathioprine/6-Meracptopurine/Methotrexate: 15/52 Corticosteroids: 29/52
Conrad et al. (2016)²²	300 mg	21/21	Infliximab: 20/21, Adalimumab: 13/21 Certolizumab: 2/21, golimumab: 1/21	Azathioprine, MP 6-mercaptopurine: 1/21 methotrexate: 8/21 Corticosteroids: 15/21
Ledder et al. (2017)²³	300 mg (n = 52); 150–250 mg (3.6–10.3 mg/kg) (n = 12)	64/64	Anti-TNF-αc, Tacrolimus: 4/64, Thalidomide: 1/64	Azathioprine/6-Mercaptopurine/Methotrexate: 21/64 Corticosteroid: 41/64
Schneider et al. (2018)²⁴	6 mg/kg (Max 300 mg)	12/12	Infliximab: 12/12. Adalimumab: 11/12 golimumab: 1/12	Corticosteroid: 8/11 Azathioprine: 3/11 5-A: 2/11
Olbjørn et al. (2020)²⁵	300 mg	8/8	Infliximab: 8/8, Corticosteroids: 8/8 azathioprine: 3/8, Methotrexate: 3/8 5-Amino salicylic acid: 5/8	Infliximab: 8/8
Jossen et al. (2020)²⁶	⩾ 30 kg: 300 mg 19–29 kg: 6–10 mg/kg	36/68	Not reported	Corticosteroid: 44/68
Dolinger et al. (2021)²⁷	300 mg	13/13	Anti-TNF-αc	Not reported
Fabiszewska et al. (2021)²⁸	150 or 300 mg, depending on the patient’s weight	15/16	Infliximab: 15/16, Adalimumab: 9/16 Other biologics: 4/16, Corticosteroid: 16/16 Budesonide: 8/16, 5-amino salicylic acid: 15/16, Azathioprine: 14/16 Cyclosporine: 10/16	During the induction phase: Azathioprine: 5/16 Methotrexate: 4/16 Corticosteroids: 8/16 During the maintenance phase: Azathioprine: 4/14 Methotrexate: 4/14 Corticosteroid: 6/14
Garcia-Romero et al. (2021)²⁹	<40 kg: 6 mg/kg (n = 20) 300 mg (n = 22)	42/42	Infliximab: 40/42 Adalimumab: 26/42 Adalimumab + Infliximab: 24/42 Oral corticosteroid: 39/42 IV corticosteroid: 28/42 Azathioprine: 40/42 6-Mercaptopurine: 4/42 Methotrexate: 12/42 Cyclosporine: 5/42 5-Amino salicylic acid: 34/42	Corticosteroid: 22/42 Azathioprine: 19/42 6-Mercaptopurine: 1/42 Methotrexate: 6/42 5-Amino salicylic acid: 22/42 Tacrolimus: 2/22
Hajjat et al. (2021)³⁰	At VED start: 6.0 ± 1.8 mg/kg; At VED end: 5.2 ± 1.9 mg/kg	136/159	Infliximab: 132/159 Adalimumab: 66/159 Golimumab: 2/159 Certolizumab: 14/159 Ustekinumab: 5/159 Corticosteroids: 105/159 Azathioprine: 16/159 6-Mercaptopurine: 48/159 Methotrexate: 82/159 5-Amino salicylic acid: 78/159 Sulfasalazine: 19/159 Rectal therapy: 72/159	Corticosteroids: 101/159 Azathioprine: 9/159 Methotrexate: 46/159
Kakiuchi and Yoshiura (2022)³¹	300 mg on day 1, week 2, and 6 and every 8 weeks thereafter	Not reported	All were on amino salicylic acid and corticosteroid	6/8 Amino salicylic acid 1/8 Azathioprine Tacrolimus 1/8
Hyams et al. (2022)³²	⩾30 kg, 150 or 300 mg <30 kg, 100 or 200 mg on day 1 and weeks 2, 6, and 14	15/44	Not reported	18/44 corticosteroids 16/44 immunomodulators
Yokoyama et al. (2023)³³	5–10 mg/kg (max 300 mg) at week 0, 2, and 6, followed by a maintenance dose of 8-week interval (4–8 weeks in some patients)	Not reported	Corticosteroid 45/48 Immunomodulator 37/48 Tacrolimus 22/48 Granulocyte apheresis 3/48 Aminosalicylic acid 18/48 Prior biologics 35/48	Aminosalicylic acid 30/48 Corticosteroids 17/48 Immunomodulator 27/48 Tacrolimus 12/48
Atia et al. (2024)³⁴	177 mg/m² Maximum dose 300 mg	Not reported	Not reported	Not reported

PUCAI, pediatric ulcerative disease activity index; VDZ, Vedolizumab.

Table 3.

Patients’ characteristics within the included studies.

Study ID	UC or IBD unclassified	Number of patients	Age years at vedolizumab initiation: median (range)/mean ± SD	Baseline severity	Disease behavior^a
Study ID	UC or IBD unclassified	Number of patients		PUCAI median (range)/pMS score median (range)/mean ± SD	Disease behavior^a
Singh et al. (2016)²¹	UC	52	14.9 (7–17)	30 (IQR 10–55)	Not reported
Conrad et al. (2016)²²	UC/IBD-U	21	13–18 (n = 15); 19–21 (n = 6)	30.0 (IQR 20.0–35.0)	B1 9/16, B2 3/16, B3 2/16, B2&B3 2/16, P 8/16
Ledder et al. (2017)²³	UC/IBD-U	64	10.7 ± 3.6	45 (IQR 30–65)	B1 17/23, B2 5/23, B3 1/23, P 4/23, G 15/23
Schneider et al. (2018)²⁴	UC/IBD-U	12	15 (8–17)	Median: 70	Not reported
Olbjørn et al. (2020)²⁵	UC	8	17 (14–17.5)	67.5 (IQR 55.63–73.75)	B1 2/4, B3 2/4, P 1/4
Jossen et al. (2020)²⁶	UC	68	16.4 (IQR 13.3–18.2)	pMS: Anti-TNF naïve: 3.5 (2–5) pMS: Anti-TNF exposed: 6 (3–6.5)	B1 29/33, B2 3/33, B3 1/33, P 10/33
Dolinger et al. (2021)²⁷	UC/IBD-U	13	15.9 (IQR 13.5–16.9)	pMS: 4 (IQR 0–7)	B1 6/7, B2 1/7
Fabiszewska et al. (2021)²⁸	UC	16	6.5 (2.2–16.5)	26 ± 6	NR
Garcia-Romero et al. (2021)²⁹	UC	42	12.6 (IQR 8.9–14.0)	47 (IQR 25–65)	B1 13/14, B2 0/14, B3 1/14, G 5/14
Hajjat et al. (2021)³⁰	UC/IBD-U	159	14.5 ± 2.4	50 (IQR 35–65)	B1 44/78, B2 17/78, B3 6/78, B2&B3 11/78
Kakiuchi and Yoshiura (2022)³¹	UC	8	12 (8–14)	2 patients PUCAI ⩾65 FC was elevated in 3 patients	Severe UC 2/8, 8/8 pancolitis, FC elevated in 3/8
Hyams et al. (2022)³²	UC	44	13.5 (2.5)	Moderate-severe UC Mayo's score of 6–12 Subscore of stool frequency and rectal bleeding of ⩾4, and an endoscopy subscore of ⩾2	PUCAI score for patients with body weight ⩾ 30 kg 46.5 (16.9) And for patients less than 30 kg 50.4 (19.8)
Yokoyama et al. (2023)³³	UC	48	14 (4–18)	36/48 had PUCAI ⩾10	E1/E2/E3 = 0, E4 = 48, S0 = 18, S1 = 30
Atia et al. (2024)³⁴	UC/IBD-U	77	13.6 (3.6) Mean	PUCAI score = 25	The median PUCAI score in children with UC decreased from 25 (IQR 15–50) at baseline to 5 (0–25) at week 54 (median of difference −10 (−30 to 0))

Paris classification was used to classify disease behavior.

B1, Nonstricturing; B2, Stricturing; B3, Penetrating; FC, fecal calprotectin; IBD, inflammatory bowel disease; IQR, interquartile range; NR, not reported; P, perianal; pMS, partial Mayo score; PUCAI, Pediatric Ulcerative Disease Activity Index; SD, standard deviation; UC, ulcerative colitis.

Clinical remission

For UC/IBD-U patients, the short-term clinical remission rate ranged from 40% to 41% at 2 weeks of treatment^21,24; in the other four investigations, it ranged from 20% to 64% at 6 weeks.^21–24 In 10 investigations, remission occurred in 20%–79.2% of patients at week 14.^{21–24,28,29,31–34} At 22 weeks, three studies found that 40%–71%,^21–23 while at 24 weeks, one study found that 53%,³⁰ 65%–75% at 30 weeks (three studies),^21,29,33 and 25%–65.8% after 1 year following maintenance therapy (five studies).^{23,29–31,33}

CS-free clinical remission

For UC/IBD-U patients, the short-term CS-free therapeutic remission rate after 6 weeks was 0%.²² By contrast, it went from 0% to 19% at week 14 (three studies)^22–24; 13%–33% at 22 weeks (three studies)^21–23; according to one study, 41% at 24 weeks³⁰; 71% at 26 weeks (one study)²⁷; 0% at 38 weeks (one study)²⁴; and 45% at 1 year (one study).³⁰

CS-free clinical remission rates in UC patients ranged from 20% to 44% at 14 weeks in three studies^21–23; 40%–71% at 22 weeks (three studies)^21–23; 49% at 24 weeks (one study)³⁰; and 78% at 26 weeks (one study).²⁷ Clinical cure was seen in 80% at 38 weeks (one study),²⁴ and 41% at 1 year (one study).³⁰

Clinical response

The rate of clinical response in one study for the included UC/IBD-U patients was 20% at 2 weeks²⁴; 25% at 6 weeks²²; and 50%–75% at 14 weeks in the other five studies^{22,28,29,31,32}; half of the included patients (50%) at 22 weeks in other study²²; 78%–79.2% at 30 weeks; and 65.6%–71% at 1 year in two studies.^29,33 Table 4 displays the combined findings for response rates, both the CS-free clinical remission and clinical remission rates.

Table 4.

Efficacy of vedolizumab on pediatric UC.

Outcome measures at a specific time and number of studies						Mucosal healing rate among assessed patients
Remission		Corticosteroid-free clinical remission		Response		Mucosal healing rate among assessed patients
2 weeks	2	6 weeks	1	2 weeks	1	24 weeks^a	2/13 = 15%
6 weeks	6	12 weeks	1	6 weeks	2	49 weeks^b	12/35 = 34%
12 weeks	1	14 weeks	3	14 weeks	3
14 weeks	9	22 weeks	3	22 weeks	1
22 weeks	3	24 weeks	1	30 weeks	1
24 weeks	1	26 weeks	1	1 year	1
30 weeks	3	38 weeks	1
1 year	5	1 year	3

Ledder et al.²³

Jossen et al.²⁶

UC, ulcerative colitis.

Healing of the mucosa

Three studies looked into the healing of the mucosa; nonetheless, one study’s small sample size (n = 8) prevented it from drawing firm conclusions.²⁸ Results of mucosal healing were reported in the other two investigations, which included 87 patients in total.^23,26 With varying evaluation times, mucosal healing was seen in 15%–34% of UC/IBD-U patients (n = 48). Table 4 gives further details on the number of patients and evaluation times.

Safety

Safety outcomes, including information on any AEs and serious adverse events (SAEs), were reported in 13 studies (n = 567).^{21–25,27–34} Two studies provided the total number of AEs rather than the percentage of participants who experienced AEs.^22,29 Nine trials showed serious AE rates, with three reporting rates ranging from 6.25% to 38.1%,^22,24,27 and six reporting nil.^{21,23,25,28–30} Headaches were the most frequent AEs, followed by respiratory tract infections and nausea/vomiting.

In the clinical assessment of vedolizumab therapy, a range of SAEs were reported. The most frequently occurring SAEs, each with 11 reported instances, included colectomy, synovitis, acne, pustulosis, hyperostosis, osteitis, severe systemic allergic reactions, obstructing nephrolithiasis with pyelonephritis, septic arthritis, and diverting ileostomy. Other, less common but noteworthy events comprised dehydration and vomiting (four occurrences), disease flare-ups (three occurrences), and bowel-associated dermatosis-arthritis syndrome (one occurrence). Furthermore, isolated cases of other SAEs were documented, such as synovitis, acne, pustulosis, hyperostosis, osteitis, obstructing nephrolithiasis with pyelonephritis, severe systemic allergic reactions, septic arthritis, deep vein thrombosis, and viral infections. These findings underscore the diverse array of potential AEs associated with vedolizumab therapy, although the overall incidence of these events remains relatively low.

In addition to the SAEs, various non-SAEs were also reported. The most common AEs included respiratory tract infections, nausea and vomiting, and headaches, each occurring in 14–16 patients. Other frequently reported AEs included fatigue (nine occurrences), mild non-urticarial rashes (seven occurrences), and arthralgia or joint pain (six occurrences). Less prevalent AEs included dizziness (five occurrences), skin infections, dermatitis, and rhinitis (two occurrences each), as well as erythema nodosum, allergic reactions, and fever (two occurrences each). In addition, a range of single-occurrence AEs was noted, including otitis externa, periorbital edema, intractable itch, new perianal disease, septic arthritis, deep vein thrombosis, cholangitis, isolated cases of paresthesia, alopecia, anemia, herpes zoster, impetigo, psoriasis, and exanthema. These observations indicate that, although vedolizumab therapy is generally well-tolerated, there exists a broad spectrum of potential AEs, which vary in both frequency and severity.

Discussion

This systematic review found that the majority of pediatric data regarding vedolizumab’s safety and effectiveness in treating IBD were descriptive. Furthermore, because all of the included studies were case series rather than randomized controlled trials, the data that were presented were limited.

Overall, we identified that 20%–64% of UC patients experienced clinical remission after receiving brief therapy. Clinical remission was attained by 20%–77% of UC/IBD-U patients undergoing maintenance treatment. Despite the modest sample sizes, clinical response rates for UC/IBD-U patients varied from 20% to 78%. Contrary to other adult research findings, the data demonstrated a similar therapeutic response for UC.

Clinical remission and response rates were higher in UC than in CD, according to the real-world Canadian and Hungarian cohorts.^35,36 Higher clinical response and remission rates in CD were observed at 14 weeks (85% vs 52%), 24 weeks (84% vs 56%), and 52 weeks (59% vs 25%), according to research conducted in Italy by Dragoni et al.³⁷ Small sample sizes and variations in baseline patient variables, such as IBD phenotype, illness severity at the onset of vedolizumab medication, and disease duration, may be the cause of variations in these results.

Considering that prolonged use of corticosteroids may result in significant adverse consequences. For pediatric IBD patients, attaining either clinical or endoscopic CS-free remission by growth restriction and osteopenia is a crucial therapeutic goal.^38,39 However, an adult meta-analysis found that 42% of UC patients at 12 months had CS-free remission, compared to only 25% after 14 weeks.⁴⁰ In the current research, similar outcomes were seen, with 20%–44% of patients achieving CS-free remission at 14 and 22 weeks.

However, different results have been found in real-world studies. Zingone et al. discovered that better outcomes were achieved in CD at all follow-up times compared to UC patients because more UC patients had continued corticosteroid use at baseline. These included higher rates of CS-free remission at 8–12 weeks (53.6% vs 18.7%), 30 weeks (56.5% vs 25%), and 52 weeks (53.6% vs 35.4%).⁴¹

Even while mucosal healing is a key therapy goal linked to long-lasting clinical remission, children may find frequent endoscopies to be tiring. As a result, only two small-scale studies with median follow-up times longer than 6 months showed mucosal healing rates. Mucosal healing rates for UC/IBD-U patients ranged from 15% to 34%, according to these investigations. The majority of research uses an endoscopic Mayo subscore of 0 for UC.²⁰ A stricter definition of mucosal healing, encompassing histologic and endoscopic (macroscopic) indications, was employed by one study in our review.²⁶ whereas mucosal healing rates for UC in adult populations have been reported to range from 15.1% to 57.1%, regardless of the patient’s baseline characteristics.^39,41,42

The potential impact of prior anti-TNF treatment on vedolizumab efficacy is a topic of much debate. Post hoc analysis from the GEMINI trials revealed that UC patients who had never used anti-TNF had higher response and remission rates than those who had.^43,44 Real-world studies have yielded contradictory results despite the limited sample size of anti-TNF-naïve patients; some have suggested that prior anti-TNF exposure had no appreciable impact on vedolizumab’s efficacy.^35,45 At week 14, patients who were anti-TNF naïve, those who failed one anti-TNF, and those who failed several anti-TNF treatments had remission rates of 57.6%, 51.2%, and 44%, respectively, according to Sands et al.⁴³ Similarly, Kotze et al.³⁵ found that prior anti-TNF failure had no bearing on vedolizumab’s efficacy in UC.

Interestingly, Mader’s study showed that vedolizumab’s effectiveness was significantly decreased in UC patients but not in CD patients due to previous anti-TNF medication. This might be because UC patients with anti-TNF experience had longer disease durations.⁴⁶ Jossen et al.²⁶ discovered that in pediatric populations, patients who had never taken anti-TNF had higher rates of endoscopic and histologic remission than those who had previously used anti-TNF (66% vs 42% for endoscopic, 52% vs 33% for histologic remission). The researchers found that the baseline disease of the anti-TNF-naïve patients was slightly less severe than that of the anti-TNF-experienced patients. Further research is required to ascertain whether these differences are due to the biological effects of anti-TNF medication and its influence on the severity and duration of disease in patients beginning vedolizumab.

According to phase II and phase III trials, vedolizumab has a favorable safety profile and an AE rate that is comparable to that of a placebo.^47,48 Real-world cohort studies show that the incidence rate of AEs is 23.6% and that infectious complications occur in 7.8% of cases.⁴⁸ In pre-marketing trials, the most common AEs were respiratory tract infections (21.2/100 person-years) and abdominal discomfort (12.1/100 person-years),^47,48 and the most frequent AEs were arthralgia (3.1%) and respiratory tract infections (3.6%), respectively.⁴⁸ Consistent with findings from adult populations, the most frequent AEs in this review were headache, nausea, vomiting, and respiratory tract infections. However, Conrad et al.²²’s study revealed that 12 SAEs happened in 38% of participants (8 out of 21) who needed to be admitted to the hospital.

Several AEs linked to vedolizumab in pediatric UC are highlighted in the safety data from this review, with varied rates and severity among studies. Headaches, nausea/vomiting, and respiratory tract infections were the most frequently reported AEs, which are in line with the usual side effects of immunosuppressive treatments. Given that these side effects were mostly mild to moderate, it is possible that most pediatric patients may take vedolizumab well. Nonetheless, these frequent AEs, especially respiratory tract infections, highlight the necessity of close observation for infections while undergoing treatment. Despite being less common, SAEs might cause safety issues. Multiple cases (11 occurrences each) of colectomy and various severe sequelae, including osteitis, acne, pustulosis, synovitis, and hyperostosis, were recorded, suggesting that some patients may experience severe inflammatory or immunological reactions. These occurrences are alarming because they can be signs of more serious autoimmune or inflammatory conditions that call for medical attention. It is also noteworthy that there were 11 cases of severe systemic allergic reactions, which could be dangerous for young patients undergoing biologic treatments. Eleven patients had further SAEs, such as deep vein thrombosis, obstructive nephrolithiasis with pyelonephritis, and septic arthritis. The incidence of these relatively uncommon but serious events emphasizes the necessity of continuous monitoring for infections, thromboembolic events, and other systemic responses while on vedolizumab. Certain SAEs, including deep vein thrombosis and septic arthritis, are especially worrisome because they may necessitate immediate medical attention and may make treating UC more difficult. Even though the data points to a generally positive safety profile for vedolizumab, variations in reported AE and SAE rates among trials could be due to variations in patient groups, study designs, and follow-up periods. More research is required to determine the long-term safety of vedolizumab in children and adolescents with UC, as the prevalence of significant AEs, especially those associated with autoimmune diseases and colectomy, calls for careful interpretation.

It is important to note that the true incidence of rare or long-term AEs may not be adequately recorded because the studies included in this evaluation were rather small. Clarifying the actual safety profile of vedolizumab in this population will require larger, more varied cohorts with longer follow-up times.

There are various restrictions on this review, and it is important to recognize the various limitations of this systematic review. First, there was a great deal of variety in the trial designs, including different criteria for including patients and different definitions of response, remission, and healing of mucosa. The majority of research used the Pediatric Ulcerative Disease Activity Index, even though other metrics were available. While one study by Jossen et al.²⁶ also took histological changes into account, most investigations focused solely on endoscopic evaluation in relation to mucosal healing.

Heterogeneity in outcome criteria across included studies, especially with relation to mucosal healing, is a drawback of this evaluation. Direct comparisons and synthesis of results are made more difficult by the fact that different studies used different criteria to evaluate mucosal healing. Others needed histologic remission, such as the absence of neutrophils or the use of validated indicators like the Geboes score, while others defined mucosal healing based on endoscopic findings, typically using the Mayo endoscopic subscore (healing being defined as a score of 0 or 1). Fecal calprotectin was used in a small number of studies as a noninvasive indicator of mucosal inflammation. These measurements show different facets of disease activity: histology confirms inflammation resolution under a microscope, endoscopy shows surface healing, and calprotectin levels show more widespread intestinal inflammation but lack anatomical specificity.

Furthermore, all of the included studies were either prospective or retrospective case series. Clinical decision-making may have varied as a result of these distinctions. Since there were no standardized, placebo-controlled trials, it was not possible to definitively attribute the observed efficacy to vedolizumab alone. Furthermore, it is challenging to determine the causal linkages between interventions and results because of the recurrent nature of UC. It is crucial to remember that vedolizumab is usually prescribed for young children whose condition is severe or refractory and who are unlikely to undergo spontaneous remission. Moreover, direct comparisons were difficult, and a formal meta-analysis was not possible due to differences in study design, patient groups, vedolizumab dosage schedules, and definitions of clinical outcomes, including remission and response. The statistical power and generalizability of the results may be diminished by the small sample sizes used in different investigations. Finally, research with negative or equivocal results may be less likely to be published, which could lead to publication bias. Lastly, there is a possibility of publication bias, as studies with negative or inconclusive results may be less likely to be published.

Conclusion

In addition to having a respectable safety profile, about half of the included patients experienced remission after 22 weeks and after a year. To further evaluate the safety and effectiveness of vedolizumab in pediatric IBD, additional solid evidence and long-term data on the benefit profile are required.

Supplemental Material

sj-docx-1-tag-10.1177_17562848251356063 – Supplemental material for A systematic review of vedolizumab in treating pediatric ulcerative colitis: efficacy and safety insights

Supplemental material, sj-docx-1-tag-10.1177_17562848251356063 for A systematic review of vedolizumab in treating pediatric ulcerative colitis: efficacy and safety insights by Khawla Abu Hammour, Adnan Abu Hamour, Faris El-Dahiyat, Mohammed Zawiah and Rana K. Abu-Farha in Therapeutic Advances in Gastroenterology

Supplemental Material

sj-docx-2-tag-10.1177_17562848251356063 – Supplemental material for A systematic review of vedolizumab in treating pediatric ulcerative colitis: efficacy and safety insights

Supplemental material, sj-docx-2-tag-10.1177_17562848251356063 for A systematic review of vedolizumab in treating pediatric ulcerative colitis: efficacy and safety insights by Khawla Abu Hammour, Adnan Abu Hamour, Faris El-Dahiyat, Mohammed Zawiah and Rana K. Abu-Farha in Therapeutic Advances in Gastroenterology

Footnotes

Acknowledgements

None.

Declarations

ORCID iD

Mohammed Zawiah

Supplemental material

Supplemental material for this article is available online.

References

Bernstein

Eliakim

Fedail

, et al. World gastroenterology organisation global guidelines inflammatory bowel disease: update August 2015. J Clin Gastroenterol 2016; 50: 803–818.

Jakobsen

Bartek

Jr Wewer

, et al. Differences in phenotype and disease course in adult and paediatric inflammatory bowel disease—a population-based study. Aliment Pharmacol Ther 2011; 34: 1217–1224.

Fang

Song

Zhang

, et al. Efficacy and safety of vedolizumab for pediatrics with inflammatory bowel disease: a systematic review. BMC Pediatr 2022; 22: 175.

Sprakes

Ford

Warren

, et al. Efficacy, tolerability, and predictors of response to infliximab therapy for Crohn’s disease: a large single centre experience. J Crohns Colitis 2012; 6: 143–153.

Roda

Jharap

Neeraj

, et al. Loss of response to anti-TNFs: definition, epidemiology, and management. Clin Transl Gastroenterol 2016; 7: e135.

Ben-Horin

Chowers

. Loss of response to anti-TNF treatments in Crohn’s disease. Aliment Pharmacol Ther 2011; 33: 987–995.

Papamichael

Gils

Rutgeerts

, et al. Role for therapeutic drug monitoring during induction therapy with TNF antagonists in IBD: evolution in the definition and management of primary nonresponse. Inflamm Bowel Dis 2015; 21: 182–197.

Danese

. New therapies for inflammatory bowel disease: from the bench to the bedside. Gut 2012; 61: 918–932.

Lamb

O’Byrne

Keir

, et al. Gut-selective integrin-targeted therapies for inflammatory bowel disease. J Crohns Colitis 2018; 12: S653–S668.

10.

Feagan

Rutgeerts

Sands

, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2013; 369: 699–710.

11.

Sandborn

Feagan

Rutgeerts

, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med 2013; 369: 711–721.

12.

Sands

Feagan

Rutgeerts

, et al. Effects of vedolizumab induction therapy for patients with Crohn’s disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology 2014; 147: 618–627.e3.

13.

EMA. Entyvio. Summary of product characteristics. European Medicines Agency, 2024.

14.

FDA. ENTYVIO (Vedolizumab) for injection, for intravenous use. Food and Drug Administration, 2022.

15.

Lamb

Kennedy

Raine

, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68: s1–s106.

16.

Gomollón

Dignass

Annese

, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016. Part 1: diagnosis and medical management. J Crohns Colitis 2017; 11: 3–25.

17.

Harbord

Eliakim

Bettenworth

, et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: current management. J Crohns Colitis 2017; 11: 769–784.

18.

Turner

Ruemmele

Orlanski-Meyer

, et al. Management of paediatric ulcerative colitis, Part 1: ambulatory care—an evidence-based guideline from European Crohn’s and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018; 67: 257–291.

19.

Van Rheenen

Aloi

Assa

, et al. The medical management of paediatric Crohn’s disease: an ECCO-ESPGHAN guideline update. J Crohns Colitis 2021; 15: 171–194.

20.

Turner

Griffiths

Wilson

, et al. Designing clinical trials in paediatric inflammatory bowel diseases: a PIBDnet commentary. Gut 2020; 69: 32–41.

21.

Singh

Rabizadeh

Jossen

, et al. Multi-center experience of Vedolizumab effectiveness in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2016; 22: 2121–2126.

22.

Conrad

Stein

Maxwell

, et al. Vedolizumab therapy in severe pediatric inflammatory bowel disease. Inflamm Bowel Dis 2016; 22: 2425–2431.

23.

Ledder

Assa

Levine

, et al. Vedolizumab in paediatric inflammatory bowel disease: a retrospective multi-centre experience from the paediatric IBD Porto Group of ESPGHAN. J Crohns Colitis 2017; 11: 1230–1237.

24.

Schneider

A-M

Weghuber

Hetzer

, et al. Vedolizumab use after failure of TNF-α antagonists in children and adolescents with inflammatory bowel disease. BMC Gastroenterol 2018; 18: 1–7.

25.

Olbjørn

Rove

Jahnsen

. Combination of biological agents in moderate to severe pediatric inflammatory bowel disease: a case series and review of the literature. Pediatr Drugs 2020; 22: 409–416.

26.

Jossen

Kiernan

Pittman

, et al. Anti-tumor necrosis factor-alpha exposure impacts Vedolizumab mucosal healing rates in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2020; 70: 304–309.

27.

Dolinger

Spencer

Lai

, et al. Dual biologic and small molecule therapy for the treatment of refractory pediatric inflammatory bowel disease. Inflamm Bowel Dis 2021; 27: 1210–1214.

28.

Fabiszewska

Derda

Szymanska

, et al. Safety and effectiveness of Vedolizumab for the treatment of pediatric patients with very early onset inflammatory bowel diseases. J Clin Med 2021; 10: 2997.

29.

Garcia-Romero

Martinez de Zabarte Fernandez

Pujol-Muncunill

, et al. Safety and effectiveness of vedolizumab in paediatric patients with inflammatory bowel disease: an observational multicentre Spanish study. Eur J Pediatr 2021; 180: 3029–3038.

30.

Hajjat

Mosha

Whaley

, et al. Vedolizumab experience in children and adolescents with inflammatory bowel disease: a multicenter observational study. Crohns Colitis 360 2021; 3: otab039.

31.

Kakiuchi

Yoshiura

. Vedolizumab as the first-line of BioLogicals for pediatric patients with ulcerative colitis. Clin Ther 2022; 44: 1028–1032.

32.

Hyams

Turner

Cohen

, et al. Pharmacokinetics, safety and efficacy of intravenous vedolizumab in paediatric patients with ulcerative colitis or Crohn’s disease: results from the phase 2 HUBBLE study. J Crohns Colitis 2022; 16: 1243–1254.

33.

Yokoyama

Yamamoto

Nambu

, et al. Safety and efficacy of vedolizumab in pediatric patients with ulcerative colitis: multicenter study in Japan. J Gastroenterol Hepatol 2023; 38: 1107–1115.

34.

Atia

Shavit-Brunschwig

Mould

, et al. Outcomes, dosing, and predictors of vedolizumab treatment in children with inflammatory bowel disease (VEDOKIDS): a prospective, multicentre cohort study. Lancet Gastroenterol Hepatol 2023; 8: 31–42.

35.

Kotze

Almutairdi

, et al. Real-world clinical, endoscopic and radiographic efficacy of vedolizumab for the treatment of inflammatory bowel disease. Aliment Pharmacol Ther 2018; 48: 626–637.

36.

Bor

Fábián

Matuz

, et al. Real-life efficacy of vedolizumab on endoscopic healing in inflammatory bowel disease—a nationwide Hungarian cohort study. Expert Opin Biol Ther 2020; 20: 205–213.

37.

Dragoni

Bagnoli

Le Grazie

, et al. Long-term efficacy and safety of vedolizumab in patients with inflammatory bowel diseases: a real-life experience from a tertiary referral center. J Dig Dis 2019; 20: 235–242.

38.

Ruemmele

Hyams

Otley

, et al. Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee. Gut 2015; 64: 438–446.

39.

Baldwin

Kaplan

. Medical management of pediatric inflammatory bowel disease. Semin Pediatr Surg 2017; 26: 360–366.

40.

Schreiber

Dignass

Peyrin-Biroulet

, et al. Systematic review with meta-analysis: real-world effectiveness and safety of vedolizumab in patients with inflammatory bowel disease. J Gastroenterol 2018; 53: 1048–1064.

41.

Zingone

Barberio

Compostella

, et al. Good efficacy and safety of vedolizumab in Crohn’s disease and ulcerative colitis in a real-world scenario. Therap Adv Gastroenterol 2020; 13: 1756284820936536.

42.

Macaluso

Fries

Renna

, et al. Effectiveness and safety of vedolizumab in biologically naïve patients: a real-world multi-centre study. United European Gastroenterol J 2020; 8: 1045–1055.

43.

Sands

Sandborn

Van Assche

, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease in patients naïve to or who have failed tumor necrosis factor antagonist therapy. Inflamm Bowel Dis 2017; 23: 97–106.

44.

Feagan

Rubin

Danese

, et al. Efficacy of vedolizumab induction and maintenance therapy in patients with ulcerative colitis, regardless of prior exposure to tumor necrosis factor antagonists. Clin Gastroenterol Hepatol 2017; 15: 229–239.e225.

45.

Chaparro

Garre

Ricart

, et al. Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry. Aliment Pharmacol Ther 2018; 48: 839–851.

46.

Mader

Juillerat

Biedermann

, et al. Factors influencing the outcome of vedolizumab treatment: real-life data with objective outcome measurements. United European Gastroenterol J 2021; 9: 398–406.

47.

Colombel

Sands

Rutgeerts

, et al. The safety of vedolizumab for ulcerative colitis and Crohn’s disease. Gut 2017; 66: 839–851.

48.

Bye

Jairath

Travis

SPL

. Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease. Aliment Pharmacol Ther 2017; 46: 3–15.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.03 MB