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Inicio Gastroenterología y Hepatología (English Edition) Efficacy and safety of vedolizumab in the treatment of ulcerative colitis
Journal Information
Vol. 39. Issue 10.
Pages 677-686 (December 2016)
Vol. 39. Issue 10.
Pages 677-686 (December 2016)
DOI: 10.1016/j.gastre.2016.11.008
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Efficacy and safety of vedolizumab in the treatment of ulcerative colitis
Eficacia y seguridad de vedolizumab en el tratamiento de la colitis ulcerosa
Eugeni Domènecha,c,
Corresponding author
, Javier P. Gisbertb,c
a Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
b Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
c Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
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Figures (1)
Tables (2)
Table 1. Phase 2 clinical trials comparing vedolizumab against placebo in patients with active ulcerative colitis.
Table 2. Main outcomes of the GEMINI 1 phase 3 trial20,30: vedolizumab (VDZ) vs placebo.
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Integrins play a crucial role in the development and maintenance of the inflammatory process in patients with inflammatory bowel disease. Vedolizumab is a humanized monoclonal antibody with a predominantly gastrointestinal effect. It specifically inhibits leucocyte integrin α4β7, thus preventing its interaction with mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), which is involved in the migration of lymphocytes from the blood stream to the intestinal tissue. Vedolizumab is indicated in the treatment of moderate to severe active Crohn's disease and ulcerative colitis in adult patients with poor response, loss of response, or intolerance to conventional treatment or to tumour necrosis factor alpha (TNF-α) antagonists. This review presents the most relevant clinical outcomes of vedolizumab in the treatment of patients with ulcerative colitis.

Ulcerative colitis
Inflammatory bowel disease
Adhesion molecules

Las integrinas desempeñan un papel clave en el desarrollo y mantenimiento del proceso inflamatorio en pacientes con enfermedad inflamatoria intestinal. Vedolizumab es un anticuerpo monoclonal humanizado con efecto predominante a nivel intestinal. Su mecanismo de acción consiste en una inhibición específica de la integrina α4ß7 de los leucocitos, lo que impide su interacción con la molécula de adhesión celular adresina de la mucosa 1 (MAdCAM-1) que participa en la migración de los linfocitos desde el torrente sanguíneo al tejido intestinal. Vedolizumab está indicado para el tratamiento de la enfermedad de Crohn y la colitis ulcerosa activas, de moderadas a graves, en pacientes adultos que hayan tenido una respuesta inadecuada, presenten pérdida de respuesta o sean intolerantes al tratamiento convencional o a un antagonista del factor de necrosis tumoral α (TNF-α). En esta revisión se presentan los resultados clínicos más importantes de vedolizumab en el tratamiento de pacientes con colitis ulcerosa.

Palabras clave:
Colitis ulcerosa
Enfermedad inflamatoria intestinal
Moléculas de adhesión
Full Text

Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease of the colonic mucosa. It almost invariably affects the rectal mucosa, extending proximally in an uninterrupted pattern, and can affect the entire colonic mucosa. UC is classified phenotypically by the extent of colon involvement, from proctitis to extensive colitis.1

Both UC and Crohn disease (CD) develop from an inappropriate immune response in genetically susceptible subjects, as a result of complex interactions between environmental and microbial factors and the intestinal immune system.2 The pathophysiological mechanisms proposed in UC include epithelial barrier dysfunction, rupture of the homeostatic equilibrium between the immunity of the host mucosa and the microbiota, activation of the toll-like receptors of the dendritic cells, dysregulated immune responses at the level of the mucosa and lamina propria of the inflamed colon (with participation of T-helper and NK cells, interleukins 5, 10 and 13, Th2 cell-related cytokines and tumour necrosis factor a [TNF-α], among others), leucocyte recruitment and trafficking and, finally, various genetic factors. Better understanding of the mechanisms that induce and perpetuate inflammation of the colonic mucosa have identified new therapeutic targets and led to the development of new drugs with different mechanisms of action.3

Leucocyte trafficking and integrin antagonists

Lymphocytes play a key role in the pathogenesis of UC. Integrin inhibitors are a group of drugs whose therapeutic target is to block leucocyte adhesion and trafficking systems and thereby reduce inflammation.4 The ability to alter the intrinsic mechanisms of adhesion and transmigration of the T-lymphocytes across the endothelial cells of the inflamed intestine may help resolve the existing inflammation and facilitate long-term control of UC.5,6

Leucocyte migration from the bloodstream across the intestinal endothelium occurs through a series of mechanisms based on adhesion systems involving integrins α4β1 and α4β7 as well vascular cell adhesion molecule 1 (VCAM-1) and mucosal addressin cellular adhesion molecule 1 (MAdCAM-1).6–8 Integrin α4β7 is expressed in a specific subtype of memory T helper cells that mainly migrate to the gastrointestinal (GI) tract and cause the inflammation characteristic of UC.9 Once transendothelial leucocyte migration has taken place, the inflammatory process spreads as a result of local proliferation and activation of lymphocytes and reduction of lymphocyte output from the mucosa. Adhesion molecules also participate in the interaction between T cells and the dendritic or mesenchymal cells of the intestinal mucosa and submucosa, facilitating T cell activation.10 The α4 integrins also play an important role in the inflammatory process by interacting with various tissue ligands which, in turn, induce co-stimulatory signals that lead to T lymphocyte proliferation and adhesion, cytokine production and increased T cell expression of the matrix metalloproteinases that degrade the extracellular matrix and facilitate cell migration.11 Thus, interruption of adhesion molecule interactions may be effective in decreasing T cell recruitment, inhibiting local co-stimulation signals, or a combination of both (Fig. 1).

Figure 1.

Process of lymphocyte migration from the blood vessels to the intestinal mucosa and mechanism of action of vedolizumab. ICAM-1, intercellular adhesion molecule 1; MAdCAM-1, mucosal vascular addressin cell adhesion molecule 1; PSGL-1, P-selectin glycoprotein ligand 1; VCAM-1, vascular cell adhesion molecule 1.

Vedolizumab in the treatment of ulcerative colitis

Treatment of UC essentially depends on the severity of the flares and response to corticosteroids. In fact, half of patients with UC will never require corticosteroid treatment and, therefore, will not require any other drugs apart from aminosalicylates.12 Among patients who require oral or intravenous corticosteroids, half will require immunosuppressive treatments, either for corticosteroid refractory- or dependent-disease.13 Vedolizumab, like infliximab, adalimumab and golimumab (the 3 anti-TNF-α drugs approved in Spain for the treatment of UC), is approved for the treatment of patients with active UC when conventional treatment (understood as treatment with corticosteroids or thiopurine immunosuppressants) has failed. Apart from this indication, vedolizumab could be a very interesting therapeutic alternative in primary failure or in secondary loss of response to anti-TNF-α treatment.

Vedolizumab is a recombinant humanised monoclonal IgG1 antibody that acts as a selective inhibitor of the α4β7 heterodimer, thus inhibiting adhesion and migration of leukocytes towards the GI tract.14 The drug is an integrin α4β7 antagonist with no identified immunosuppressant activity. By binding to α4β7 on certain T lymphocytes, vedolizumab inhibits adhesion of these cells to MAdCAM-1, but not to VCAM-1.15 The adhesion molecule MAdCAM-1 is expressed in the intestine and in gut-associated tissues (such as the pancreas) and lymphoid tissue (such as Peyer's patches, or intestinal lamina propria).16 It is not generally detected in most extra-intestinal tissues (normal or inflamed), including those with mucosal surfaces, or in the endothelium of the veins of the lung, liver, kidney, heart, salivary glands, uterus, ovary, skeletal muscle, skin or brain parenchyma.16 However, MAdCAM-1 has been detected in liver tissue after prolonged inflammatory bowel disease-associated inflammation.17 Adhesion molecule MAdCAM-1 expressed in the endothelial cells of the intestine plays a critical role in T lymphocyte migration to the tissues of the intestinal tract. Unlike natalizumab, vedolizumab does not bind to or inhibit the function of integrins α4β1 and αEβ7, and because it does not induce alterations in systemic immunosuppression, it does not affect the immune surveillance mechanisms of the central nervous system (CNS). Therefore, although natalizumab treatment is associated with an increased risk of progressive multifocal leukoencephalopathy (PML), a progressive demyelinating disease of the CNS caused by an opportunistic human polyomavirus (the John Cunningham or JC virus), during the clinical development of vedolizumab, which included approximately 3000 patients (mean exposure 19 months), no cases of PML were reported in patients treated with vedolizumab, despite the fact that more than 80% of patients had received immunosuppressive treatment prior to inclusion in the study.18–20

In May 2014, the United States Food and Drug Administration and the European Medicines Agency gave marketing approval for vedolizumab (Entyvio®, Takeda Pharmaceuticals International GmbH) for the treatment of moderately to severely active CD and UC in adults who have had an inadequate response with, lost response to or are intolerant to conventional treatment or to a TNF-α antagonist.21

Efficacy of vedolizumab in patients with ulcerative colitis

Previous versions of vedolizumab were called LDP-02, MLN02 and MLN0002. For clarity, in this review we will refer to all versions as “vedolizumab”. Phase 1 studies in healthy volunteers have confirmed the gut-selective mechanism of action of vedolizumab,22 absence of effect on the lymphocytes in the cerebrospinal fluid (CD4+: CD8+ ratio)23 and similarity in the pharmacokinetic parameters in patients with UC and CD, with no need for dose variation in the presence of covariables such as age, sex, weight, presence of anti-vedolizumab antibodies and albumin.24

Similarly, different phase 2 studies in patients with active UC have provided efficacy, safety, tolerability and pharmacokinetic data (Table 1). In 46 patients included in a randomised, double-blind, placebo-controlled study treated with vedolizumab (2, 6 or 10mg/kg) or placebo on days 1, 15, 29 and 85, and monitored for 8 months, vedolizumab showed dose-proportional pharmacokinetics, with saturation of the α4β7 receptors on peripheral blood lymphocytes.25,26 Another study with 29 patients with moderate-severe UC compared various doses of vedolizumab (0.15mg/kg subcutaneously or 0.15, 0.5 or 2mg/kg intravenously [i.v.]) with placebo. The 0.5mg/kg dose was sufficient to achieve saturation of the α4β7 receptors of the circulating lymphocytes for 30 days.27 In a double-blind, placebo-controlled multicentre study that included 181 patients with active UC randomised to treatment with 0.5 or 2mg/kg (or placebo) on days 1 and 29, the rates of remission were significantly higher in the active treatment group, and at week 6 were 33%, 32% and 14% for the groups treated with 0.5mg/kg, 2mg/kg and placebo, respectively (p=0.002), with endoscopic remission rates of 28%, 12% and 8%, respectively.29

Table 1.

Phase 2 clinical trials comparing vedolizumab against placebo in patients with active ulcerative colitis.

Author (reference)  Design  Participant randomisation  Dose and days of administration  Study outcomes  Results 
Scholz25  Randomised, double-blind, placebo-controlled  46 patients
37 VDZ, 9 placebo
2, 6 or 10mg/kg
Days 1, 15, 29 and 85
Follow-up to day 253 
Serum VDZ concentrations
α4ß7 saturation peripheral lymphocytes
Partial Mayo Clinic score 
VDZ dose-proportional ↑ Cmax and AUC
↓ VDZ concentration monoexponentially to 1–10μg/mL, then non-linearly
Maximum saturation of α4ß7 receptors
No saturation with placebo
Percentage of responders>50% VDZ group
22–33% in the placebo group
↓ faecal calprotectin in the VDZ group
AE: headache, UC flare, upper respiratory tract infection and nasopharyngitis 
Parikh26  Randomised, double-blind, placebo-controlled  46 patients
37 VDZ, 9 placebo
2, 6 or 10mg/kg
Days 1, 15, 29 and 85
Follow-up to day 253 
Serum VDZ concentrations
α4ß7 saturation peripheral lymphocytes
Partial Mayo Clinic score
As in the previous study
In patients with more active disease, response rates 68%-89% in patients treated with VDZ vs 25–50% in those treated with placebo 
Feagan27  Double-blind placebo-controlled, ascending dose  29 patients  0.15mg/kg s.c.
0.15, 0.5, 2.0mg/kg i.v. (groups 1–4)
30-day follow-up 
Mayo Clinic score
Baron score (sigmoidoscopy) 
0.5mg/kg dose sufficient to block the α4ß7 receptors for 30 days
Endoscopic response in 1/5, 0/5, 3/5 and 1/5 in groups 1–4 vs 2/8 in the placebo group
40% patients in group 3 showed complete endoscopic and clinical remission 
Feagan28  Randomised, double-blind, placebo-controlled, multi-centre  181 patients  Two i.v. doses of 0.5 or 2.0mg/kg on days 1 and 29 or placebo  Clinical remission defined as UC clinical score (UCCS) of 0 or 1 and modified Baron score (MBS) 0 or 1, with no blood in stools on day 43  Remission rates of 33%, 34% and 15% for the 0.5 and 2.0mg/kg doses and placebo, respectively (p=0.03). The proportion of patients with decrease of 3 points or more in the UCCS was 66%, 57% and 33%, respectively (p=0.001).
Serious AE in 8% treated with VDZ vs 5% with placebo 
Feagan29  Randomised, double-blind, placebo-controlled, multi-centre  181 patients  Two i.v. doses of 0.5 or 2.0mg/kg on days 1 and 29 or placebo  Clinical remission at week 6 defined as UC clinical score (UCCS) of 0 or 1 and modified Baron score (MBS) 0 or 1, with no blood in stools  Remission rates of 33%, 32% and 14% for the 0.5 and 2.0mg/kg doses and placebo, respectively (p=0.03). The proportion of patients with decrease of 3 points or more in the UCCS was 66%, 57% and 33%, respectively (p=0.001).
Endoscopic remission in 28% of those treated with 0.5mg/kg and 12% in those treated with 2.0mg/kg vs 8% in those treated with placebo (p=0.007) 

AE, adverse events; UC, ulcerative colitis; VDZ, vedolizumab.

The efficacy and safety of vedolizumab has been studied in a phase 3 clinical trial in patients with UC (GEMINI 1).20,30

This trial integrated the results of 2 randomised, double blind, placebo-controlled studies. It included patients with active UC, defined as a Mayo Clinic score of 6–12, with a minimum sigmoidoscopy subscore of 2, and failure of previous treatments (lack of response or adverse events), including glucocorticoids, immunosuppressants or anti-TNF-α. The induction therapy study included 2 cohorts: cohort 1 was made up of 374 patients who were treated with 300mg of vedolizumab i.v. or placebo at weeks 0 and 2, while cohort 2 (open study) was made up of 521 patients treated with vedolizumab also at weeks 0 and 2. The clinical response was evaluated in both cohorts at week 6. In the maintenance therapy study, patients from both cohorts who showed a response to vedolizumab at week 6 were randomised to continue treatment with vedolizumab every 4 or 8 weeks, or placebo up to 52 weeks. The primary outcome in the induction phase was clinical response at week 6, defined as a decrease in the Mayo Clinic score of at least 3 points and a 30% or more reduction with respect to the baseline score, with a decrease of at least 1 point in the rectal bleeding score or an absolute rectal bleeding score of 0 or 1. The secondary outcomes included clinical remission (Mayo Clinic score of 2 or lower with no rectal bleeding subscore higher than 1 and mucosal healing, defined as an endoscopic subscore of 0 or 1). The primary outcome for the maintenance phase was clinical remission at week 52, and the secondary outcomes were durable clinical response and clinical remission (at weeks 6 and 52), mucosal healing at week 52 and glucocorticoid-free remission at week 52 in patients who received this medication at baseline. Quality of life (QoL) was measured using a specific questionnaire for patients with inflammatory bowel disease (IBDQ).

In both the induction and maintenance treatment trial, the differences between the vedolizumab and placebo treatment groups were statistically significant for all the primary and secondary outcomes of interest (Table 2). Patients treated with vedolizumab also experienced more significant improvements in the partial Mayo Clinic score, IBDQ score, faecal calprotectin concentration and glucocorticoid use than patients treated with placebo. In a post hoc analysis, no clear differences were observed in the efficacy of vedolizumab administered every 4 or every 8 weeks. No differences in the most common adverse events (headache, nasopharyngitis, upper respiratory tract infection, arthralgia, nausea, abdominal pain, fatigue, anaemia and cough) were observed between vedolizumab and placebo groups, although serious infections were more common in the active treatment group (2.9% vs 1.9%). No cases of PML were observed.

Table 2.

Main outcomes of the GEMINI 1 phase 3 trial20,30: vedolizumab (VDZ) vs placebo.

Outcome of interest  Treatment group  Percentage of patients  Difference (95% CI)  p 
Induction therapy (cohorts 1 & 2)
Clinical responsePlacebo (n=149)  25.5  21.7 (11.6–31.7)<0.001
VDZ (n=225)  47.1 
Clinical remissionPlacebo (n=149)  5.4  11.5 (4.7–18.3)0.001
VDZ (n=225)  16.9 
Mucosal healingPlacebo (n=149)  24.8  16.1 (6.4–25.9)0.001
VDZ (n=225)  40.9 
Maintenance therapy
Clinical remission at 52 weeksPlacebo (n=126)  15.9  26.1 (14.9–37.2)<0.001
VDZ (n=122) every 8 weeks  41.8 
Placebo (n=126)  15.9  29.1 (17.9–40.4)<0.001
VDZ (n=125) every 4 weeks  44.8 
Sustained clinical responsePlacebo (n=126)  23.8  32.8 (20.8–44.7)<0.001
VDZ (n=122) every 8 weeks  56.6 
Placebo (n=126)  23.8  28.5 (16.7–40.3)<0.001
VDZ (n=125) every 4 weeks  52.0 
Sustained clinical remissionPlacebo (n=126)  8.7  11.8 (3.1–20.5)0.008
VDZ (n=122) every 8 weeks  20.5 
Placebo (n=126)  8.7  15.3 (6.2–24.4)0.001
VDZ (n=125) every 4 weeks  24.0 
Mucosal healing at week 52Placebo (n=126)  19.8  32.0 (20.3–43.8)<0.001
VDZ (n=122) every 8 weeks  51.6 
Placebo (n=126)  19.8  36.3 (24.4–48.4)<0.001
VDZ (n=125) every 4 weeks  56.0 
Glucocorticoid-free remission at week 52Placebo (n=126)  13.9  17.6 (3.9–31.3)0.01
VDZ (n=122) every 8 weeks  31.4 
Placebo (n=126)  13.9  31.4 (16.6–46.2)<0.001
VDZ (n=125) every 4 weeks  45.2 

95% CI, 95% confidence interval; VDZ, vedolizumab.

The results of the GEMINI 1 trial showed that vedolizumab was more effective than placebo as induction and maintenance treatment in patients with active UC. Similarly, additional analyses in other patient subgroups in this trial, including previous failure of anti-TNF-α or immunomodulatory treatment31 or patients from cohorts who were non-responders at week 6,32 also showed the superiority of vedolizumab compared to placebo at weeks 6 and 52. QoL measurement using generic instruments, such as the short form SF-36 health questionnaire and the EQ-5D questionnaire visual analogue scale, as well as the IBDQ specific questionnaire, also showed that vedolizumab has beneficial effects on patient QoL.33

Data on the long-term efficacy of vedolizumab are also available, derived from the open-label extension study of the GEMINI 1 trial (GEMINI LTS), which includes results on clinical remission up to week 104.34 Thus, in a total of 275 patients who completed the GEMINI 1 trial and received any dose of vedolizumab during the GEMINI LTS, clinical remission was obtained in 73% of cases. Similarly, in the subgroup of patients with previous failure of anti-TNF-α treatment, 65% maintained clinical remission at week 104.35 Apart from the clinical activity, preliminary findings are also available for mucosal healing at week 52, which was 28% in the vedolizumab group compared to 8.7% in the placebo group (p<0.001), with rates of endoscopic improvement and clinical remission of 31% and 13%, respectively (p<0.001).36 These studies also showed that the efficacy of vedolizumab does not differ according to age,37 baseline faecal calprotectin levels38 or concomitant use of corticosteroids or immunomodulators.39 Finally, an extension study of the GEMINI 1 trial showed the safety of re-administering vedolizumab every 4 weeks after 1 year with no treatment.40

Two systematic reviews have analysed the efficacy of vedolizumab in the treatment of UC.41,42 In one of these,41 which included 8 randomised controlled trials with biological agents (vedolizumab, abatacept, visilizumab, golimumab), vedolizumab was significantly more effective than placebo in achieving clinical response, clinical remission and mucosal healing in the induction phase, with relative benefits of 82%, 166% and 75%, respectively (p<0.001 for all comparisons); in the maintenance phase, vedolizumab achieved a significantly higher percentage of clinical remission and mucosal healing with respect to placebo (p<0.01). In the other systematic review that included 4 randomised controlled clinical trials comparing vedolizumab with placebo in a total of 606 patients, aggregated analyses showed the statistically significant superiority of vedolizumab compared to placebo for inducing remission, clinical response, endoscopic remission and maintenance of remission.42

Safety of vedolizumab treatment

The adverse events most commonly observed in patients treated with vedolizumab include nasopharyngitis, headache, nausea, arthralgia, pyrexia, fatigue, upper respiratory tract infections, cough and abdominal pain.43 The safety data described in a recent systematic review41 suggested that vedolizumab was as safe as placebo in terms of risk of adverse events, serious adverse events or deaths in the induction phase. In the maintenance phase, the risk of adverse events was also similar between patients treated with vedolizumab or placebo, but the differences between groups for the risk of serious adverse events was marginally significant (p=0.05). In a systematic review of 4 clinical trials with a total of 606 patients,42 no statistically significant difference was found between vedolizumab and placebo in terms of risk of any adverse event (relative risk [RR] 0.99, 95% confidence interval [95% CI]: 0.93–1.07) or serious adverse events (RR 1.01; 95% CI: 0.72–1.42). However, a statistically significant difference was observed in patients who withdrew due to an adverse event: 6% for vedolizumab vs 11% in the case of placebo (RR 0.55; 95% CI: 0.35–0.87; 2 studies, 941 patients). Nonetheless, no severe infections, including PML, were reported in patients with UC in the GEMINI 1 trial.20

Finally, an immunogenicity rate of 4% has been described in the GEMINI 1 and 2 controlled studies (56 of 1434 patients).30,44,45 Anti-vedolizumab antibodies were detected in approximately 10% of patients 16 weeks after the last dose of vedolizumab.30,44 In these trials, 5% of patients who presented an adverse event considered by the investigator to be infusion-related also tested positive for anti-vedolizumab antibodies. Nevertheless, in general, there was no correlation between the development of anti-vedolizumab antibodies and the clinical response or adverse events.


Vedolizumab has been shown to be more effective than placebo for inducing and sustaining clinical remission in UC in a manner similar to anti-TNF-α agents approved for the treatment of UC (infliximab, golimumab and adalimumab). Vedolizumab, like infliximab, adalimumab and golimumab (the 3 anti-TNF-α drugs currently approved in Spain for the treatment of UC), has been approved for the treatment of patients with UC in whom conventional treatment has failed. Beyond this approved indication, one of the most attractive scenarios concerns patients with previous exposure to an anti-TNF agent. The secondary loss of response to anti-TNF-α is usually managed by escalation of the same drug or by switching to another anti-TNF, strategies that usually increase costs and have shown acceptable short- but not long-term efficacy. In the 25% or so of patients who do not present a primary response to a first anti-TNF,46,47 a second anti-TNF is even less likely to be effective.48,49 It therefore seems reasonable to consider vedolizumab as the drug of choice in both situations (primary and secondary failure of an anti-TNF-α), and it can also be used as a first-line drug in case of failure or intolerance to conventional immunosuppressants (thiopurines or methotrexate).

Moreover, vedolizumab has been shown to have a good safety profile, with so far none of the neurological complications (PML) reported with other drugs that share a similar mechanism of action (integrin inhibition), which is probably explained by the gut-selectivity of vedolizumab. It is precisely this selectivity that could give it an advantage over other drugs with a more non-specific or systemic effect, such as thiopurines, calcineurines or anti-TNF-α agents. Finally, immunogenicity (i.e. the formation of antibodies against vedolizumab) seems to be rare, possibly lower that that described with anti-TNF-α drugs.

In summary, vedolizumab can be considered a promising option for the treatment (induction, and above all, maintenance) of moderate or severe UC. Its position in the therapeutic arsenal in relation to other drugs — especially anti-TNF-α agents — is not yet established. This will depend on accumulated experience with the efficacy (including more patients and longer follow-up) and safety (if the favourable safety profile described to date is confirmed) of vedolizumab. Finally, some important aspects should be clarified in the future, such as the efficacy of vedolizumab in patients with severe UC refractory to corticosteroids, or the possible synergy between this drug and traditional immunosuppressants.

Conflict of interests

The authors have received no remuneration for writing this article and have acted completely independently in its preparation, with no employee of Takeda Farmacéutica España having participated in its drafting. Takeda Pharmaceuticals International had the opportunity to review the manuscript.

E. Domènech: scientific consultancy, conferences, support for research or training activities: MSD, AbbVie, Takeda, Hospira, Kern Pharma, Ferring, Faes Farma, Shire Pharmaceuticals, Chiesi, Otsuka Pharmaceuticals, and Gebro Pharma.

J.P. Gisbert: scientific consultancy, conferences, support for research or training activities: MSD, AbbVie, Takeda, Hospira, Kern Pharma, Pfizer, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Chiesi, Laboratorios Casen Fleet, Otsuka Pharmaceutical, Uriach and Dr. Falk Pharma and Gebro Pharma.


The authors would like to thank Dr Marta Pulido and Nature Publishing Group Iberoamérica for their assistance in writing this article, with editorial support funded by Takeda Farmacéutica España.

C. Abraham, J.H. Cho.
Inflammatory bowel disease.
N Engl J Med, 361 (2009), pp. 2066-2078
T. Stefanelli, A. Malesci, A. Repici, S. Vetrano, S. Danese.
New insights into inflammatory bowel disease pathophysiology: paving the way for novel therapeutic targets.
Curr Drug Targets, 9 (2008), pp. 413-418
J.P. Gisbert, E. Domenech.
Vedolizumab in the treatment of Crohn's disease [Article in Spanish].
Gastroenterol Hepatol, 38 (2015), pp. 338-348
S. Ghosh, R. Panaccione.
Anti-adhesion molecule therapy for inflammatory bowel disease.
Ther Adv Gastroenterol, 3 (2010), pp. 239-258
I. Mitroulis, V.I. Alexaki, I. Kourtzelis, A. Ziogas, G. Hajishengallis, T. Chavakis.
Leukocyte integrins: role in leukocyte recruitment and as therapeutic targets in inflammatory disease.
Pharmacol Ther, 147 (2015), pp. 123-135
I. Marafini, S. Sedda, F. Pallone, G. Monteleone.
Targeting integrins and adhesion molecules to combat inflammatory bowel disease.
Inflamm Bowel Dis, 20 (2014), pp. 1885-1889
S. Danese, S. Semeraro, M. Marini, I. Roberto, A. Armuzzi, A. Papa, et al.
Adhesion molecules in inflammatory bowel disease: therapeutic implications for gut inflammation.
Dig Liver Dis, 37 (2005), pp. 811-818
G. Fiorino, C. Correale, W. Fries, A. Repici, A. Malesci, S. Danese.
Leukocyte traffic control: a novel therapeutic strategy for inflammatory bowel disease.
Expert Rev Clin Immunol, 6 (2010), pp. 567-572
N. Ghosh, R. Chaki, S.C. Mandal.
Inhibition of selective adhesion molecules in treatment of inflammatory bowel disease.
Int Rev Immunol, 31 (2012), pp. 410-427
C.M. Hogaboam, D.P. Snider, S.M. Collins.
Activation of T lymphocytes by syngeneic murine intestinal smooth muscle cells.
Gastroenterology, 110 (1996), pp. 1456-1466
J.A. Madri, D. Graesser, T. Haas.
The roles of adhesion molecules and proteínases in lymphocyte transendothelial migration.
Biochem Cell Biol, 74 (1996), pp. 749-757
T. Jess, L. Riis, I. Vind, K.V. Winther, S. Borg, V. Binder, et al.
Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: a population-based study from Copenhagen, Denmark.
Inflamm Bowel Dis, 13 (2007), pp. 481-489
E. Domènech, M. Mañosa, E. Cabré.
An overview of the natural history of inflammatory bowel diseases.
Dig Dis, 32 (2014), pp. 320-327
M.A. Smith, R.A. Mohammad.
Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases.
Ann Pharmacother, 48 (2014), pp. 1629-1635
K. Haddley.
Vedolizumab for the treatment of inflammatory bowel disease.
Drugs Today (Barc), 50 (2014), pp. 309-319
H. Ogawa, D.G. Binion, J. Heidemann, M. Theriot, P.J. Fisher, N.A. Johnson, et al.
Mechanisms of MAdCAM-1 gene expression in human intestinal microvascular endothelial cells.
Am J Physiol Cell Physiol, 288 (2005), pp. C272-C281
P. Rafiee, H. Ogawa, J. Heidemann, M.S. Li, M. Aslam, T.H. Lamirand, et al.
Isolation and characterization of human esophageal microvascular endothelial cells: mechanisms of inflammatory activation.
Am J Physiol Gastrointest Liver Physiol, 285 (2003), pp. G1277-G1292
K. Hellwig, R. Gold.
Progressive multifocal leukoencephalopathy and natalizumab.
J Neurol, 258 (2011), pp. 1920-1928
S. Danese, J. Panes.
Development of drugs to target interactions between leukocytes and endothelial cells and treatment algorithms for inflammatory bowel diseases.
Gastroenterology, 147 (2014), pp. 981-989
B.G. Feagan, P. Rutgeerts, B.E. Sands, S. Hanauer, J.F. Colombel, W.J. Sandborn, et al.
Vedolizumab as induction and maintenance therapy for ulcerative colitis.
N Engl J Med, 369 (2013), pp. 699-710
Takeda receives European Commission Marketing Authorisation for Entyvio® (vedolizumab) for the Treatment of Ulcerative Colitis and Crohn's Disease. Available in: http://www.takeda.com/news/2014/20140528_6590.html.
T. Wyant, T. Leach, S. Sankoh, Y. Wang, J. Paolino, B. Feagan, et al.
A phase 1, double-blind placebo-controlled single-dose study to determine the immune response to systemic and mucosal antigenic challenge in the presence of vedolizumab.
J Crohns Colitis, 7 (2013), pp. S248
C. Milch, T. Wyant, J. Xu, W. Kent, J. Berger, I.H. Fox.
Vedolizumab does not reduce the CD4+:CD8+ ratio in the CSF of health volunteers.
J Crohns Colitis, 6 (2012), pp. S102-S103
M. Rosario, N. Dirks, M. Gastonguay, I. Fox, A. Milton.
Population pharmacokinetic modelling of vedolizumab in patients with ulcerative colitis or Crohn's disease.
J Crohns Colitis, 8 (2014), pp. S225-S226
C. Scholz, T. Wyant, T. Leach, S. Sankoh, D.R. Mould, M. Patella, et al.
Clinical pharmacology of vedolizumab (MLN0002) in patients with active ulcerative colitis P164.
J Chrons Colitis, 3 (2009), pp. S75-S76
A. Parikh, T. Leach, T. Wyant, C. Scholz, S. Sankoh, D.R. Mould, et al.
Vedolizumab for the treatment of active ulcerative colitis: a randomized controlled phase 2-ranging study.
Inflamm Bowel Dis, 18 (2012), pp. 1470-1479
B.G. Feagan, J.W.D. McDonald, G. Greenberg, G. Wild, P. Pare, R.N. Fedorak, et al.
An ascending dose trial of a humanized A4B7 antibody in ulcerative colitis (CU).
Gastroenterology, 118 (2000), pp. A874
B. Feagan, G. Greenberg, G. Wild, J. McDonald, R. Fedorak, P. Pare, et al.
A randomized controlled trial of a humanized alpha4beta7 antibody in ulcerative colitis (UC).
Am J Gastroenterol, 98 (2003), pp. S248-S249
B. Feagan, G. Greenberg, G. Wild, J. McDonald, R. Fedorak, P. Paré, et al.
Treatment of ulcerative colitis with humanized antibody to the α4β7 integrin.
N Engl J Med, 352 (2005), pp. 2499-2507
B. Fragan, P. Turgeerts, B. Sands, W. Sandborn, J.F. Colombel, S. Hanauer, et al.
Vedolizumab maintenance for ulcerative colitis: results of GEMINI I, a randomized, placebo-controlled, double-blind. Multicenter phase 3 trial.
Am J Gastroenterol, 107 (2012), pp. S609-S610
B. Feagan, B. Sands, S. Sankoh, C. Milch, I. Fox.
Efficacy of vedolizumab in ulcerative colitis by prior treatment failure in GEMINI I, a randomised, placebo-controlled, double-blind, multi-centre trial.
J Crohns Colitis, 7 (2013), pp. S216
B. Feagan, W.J. Sandborn, M. Smyth, S. Sankoh, A. Parikh, I. Fox.
Effects of continued vedolizumab therapy for ulcerative colitis in week 6 induction therapy nonresponders.
J Crohns Colitis, 8 (2014), pp. S276-S277
B. Feagan, J.F. Colombel, D. Rubin, R. Mody, S. Sankoh, K. Laschó.
Improvements in health-related quality of life in patients with ulcerative colitis treated with vedolizumab.
J Crohns Colitis, 8 (2014), pp. S51-S52
B. Feagan, A. Kaser, M. Smyth, R. Panaccione, S. Sankoh, B. Abhyankar.
Long-term efficacy of vedolizumab therapy for ulcerative colitis. UEG Week 2014 Oral Presentations.
United Eur Gastroenterol J, 2 (2014), pp. A66
W.J. Sandborn, J.F. Colombel, R. Panaccione, K. Lasch, K. Sankoh, B. Abhyankar, et al.
Deep clinical remission in patients with ulcerative colitis: evaluating the effects of vedolizumab on various combinations of endoscopic and patient-reported outcomes.
J Crohns Colitis, 9 (2015), pp. S237-S238
W. Sandborn, J.F. Colombel, R. Panaccione, K. Lasch, R. Mody, R. Green, et al.
Deep remission as a predictor of clinical outcomes in vedolizumab-treated patients with ulcerative colitis.
J Crohns Colitis, 9 (2015), pp. S299-S300
V. Yajnik, N. Khan, M. Dubinsky, J. Axler, A. Green, B. Abhyankar, et al.
Efficacy and safety of vedolizumab with advancing age in patients with ulcerative colitis: results from the GEMINI 1 study.
J Crohns Colitis, 9 (2015), pp. S363-S364
W. Reinish, J.D. Lewis, T. Dassopoulos, P. Ginsburg, B.E. Sands, B. Feagan, et al.
Clinical response and remission with vedolizumab across a range of baseline fecal calprotectin levels in ulcerative colitis: results from GEMINI 1.
J Crohns Colitis, 9 (2015), pp. S47
J.F. Colombel, E.V. Loftus Jr., C.A. Siegel, J.D. Lewis, M. Smyth, S. Sankoh, et al.
Efficacy of vedolizumab with concomitant corticosteroid or immunomodulator use in patients with ulcerative colitis from GEMINI 1.
J Crohns Colitis, 9 (2015), pp. S296-S297
B.E. Sands, I. Shafran, F.A. Farraye, A.S. Cheifetz, B. Abhyankar, S. Sankoh, et al.
Efficacy and safety of retreatment with vedolizumab in patients with ulcerative colitis.
J Crohns Colitis, 9 (2015), pp. S37
P. Kawalec, A. Mikrut, S. Lopuch.
Systematic review of the effectiveness of biological therapy for active moderate to severe ulcerative colitis.
J Gastroenterol Hepatol, 29 (2014), pp. 1159-1170
S.J. Brickston, B.W. Behm, D.J. Tsoulis, J. Cheng, J.K. MacDonald, R. Khanna, et al.
Vedolizumab for induction and maintenance of remission in ulcerative colutis.
Cochrane Database Syst Rev, 8 (2014), pp. CD007571
M.A. Smith, R.A. Mohammad.
Vedolizumab: an α4ß7 integrin inhibitor for inflammatory bowel disease.
Ann Pharmacother, 48 (2014), pp. 1629-1635
W.J. Sandborn, B.G. Feagan, P. Rutgeerts, S. Hanauer, J.F. Colombel, B.E. Sands, et al.
Vedolizumab as induction and maintenance for Crohn's disease.
N Engl J Med, 369 (2013), pp. 711-721
M. Rosario, T. Wyant, C. Milch, A. Parikh, B. Feagan, W.J. Sandborn, et al.
Pharmacokinetic and pharmacodynamics relationship and immunogenicity of vedolizumab in adults with inflammatory bowel disease: additional results from GEMINI 1 and 2 studies.
J Crohns Colitis, 8 (2014), pp. S42-S43
J.P. Gisbert, J. Panés.
Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review.
Am J Gastroenterol, 104 (2009), pp. 760-767
H. Yanai, S.B. Hanauer.
Assessing response and loss of response to biological therapies in IBD.
Am J Gastroenterol, 106 (2011), pp. 685-698
S. Ben-Horin, Y. Chowers.
Review article: loss of response to anti-TNF treatments in Crohn's disease.
Aliment Pharmacol Ther, 33 (2011), pp. 987-995
J.P. Gisbert, A.C. Marín, A.G. McNicholl, M. Chaparro.
Systematic review with meta-analysis: the efficacy of a second anti-TNF in patients with inflammatory bowel disease whose previous anti-TNF treatment has failed.
Aliment Pharmacol Ther, 41 (2015), pp. 613-623

Please cite this article as: Domènech E, Gisbert JP. Eficacia y seguridad de vedolizumab en el tratamiento de la colitis ulcerosa. Gastroenterol Hepatol. 2016;39:677–686.

Copyright © 2016. Elsevier España, S.L.U. and AEEH y AEG
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