Sage Journals: Discover world-class research

Abstract

Vedolizumab (VED) is a gut-selective monoclonal antibody and an effective biological agent for many patients with inflammatory bowel disease (IBD). Therapeutic drug monitoring has been used to optimise treatment with other biological agents; however, the clinical applicability of measuring vedolizumab trough concentrations is unclear. Initial registration trial data demonstrated a positive exposure–efficacy relationship of vedolizumab in IBD. However, there is conflicting data in more recent studies, with no definitive benefit of vedolizumab dose-escalation and no consistent target vedolizumab trough concentration identified. Also, unlike with anti-tumour necrosis factor agents, the clinical benefit of immunomodulator co-therapy with vedolizumab is uncertain. Although initial research suggested no clinical advantage of combining vedolizumab with an immunomodulator, more recent studies have shown potential benefit. This narrative review aims to explore current evidence on vedolizumab pharmacokinetics and whether immunomodulator co-therapy should be considered with vedolizumab.

Plain language summary

Vedolizumab: how it works and if it should be combined with other medications in inflammatory bowel disease

This article reviews how the medication vedolizumab works in the body (called pharmacokinetics) when used to treat people with inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis. It also looks at how using vedolizumab together with other immune-suppressing drugs (called immunomodulators) might affect its effectiveness. The goal is to help doctors better understand how to use these treatments together to manage IBD more effectively.

Keywords

Crohn’s disease immunomodulator pharmacokinetics ulcerative colitis vedolizumab

Introduction

Inflammatory bowel disease (IBD), consisting of ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic health condition characterised by inflammation affecting the gastrointestinal tract.^1,2 Symptoms include diarrhoea, abdominal pain, rectal bleeding, fatigue and weight loss. Whilst prevalence rates of IBD have been increasing over time, the therapeutic armamentarium has expanded over the last two decades.^3,4 Particularly, biological and oral small-molecule agents have revolutionised the management of IBD. These medications target various immunological pathways that have been implicated in the pathogenesis of IBD. However, the only current advanced therapy that selectively targets the gastrointestinal tract is vedolizumab (VED).⁵

VED (Entyvio; Takeda Pharmaceutical Company Ltd, Tokyo, Japan) is a humanised IgG₁ monoclonal antibody that specifically binds to the α4β7 integrin, which is preferentially expressed on gut-homing T-helper lymphocytes.⁵ This binding inhibits the adhesion of these lymphocytes to mucosal-addressin-cell-adhesion molecule-1, which is predominantly found on endothelial cells of the gastrointestinal tract and involved in T lymphocyte migration (Figure 1).^5,6 As such, VED selectively blocks leukocyte trafficking to the gastrointestinal tract.⁷ The GEMINI 1 and VISIBLE 1 randomised controlled trials found that intravenous (IV) and subcutaneous (SC) VED, respectively, led to superior rates of clinical and endoscopic remission versus placebo at week 52 in UC.^8,9 Similarly, higher rates of clinical remission were seen with IV and SC VED in CD in the GEMINI 2 and VISIBLE 2 trials.^10,11

Figure 1.

Mechanisms of action of advanced therapies in inflammatory bowel disease.

Therapeutic drug monitoring (TDM) involves measuring drug and anti-drug antibodies, differentiating underexposed patients from those with mechanistic failure.¹² It is a proven strategy to optimise the effectiveness of anti-tumour necrosis factor (anti-TNF) antagonists, and although its use is not fully implemented in routine clinical practice, it forms part of consensus statements and management guidelines.^13–16 One strategy that has also been shown to reduce the risk of anti-drug antibody formation and resultant loss of response is combining anti-TNF therapy with an immunomodulator.¹⁷ However, unlike with anti-TNF therapy, there are no guidelines on target VED trough levels despite its use for over a decade. The role of measuring VED trough levels is currently not standard practice, and there has been mixed data regarding the efficacious role of combining an immunomodulator with VED. We aimed to examine the evolving literature on TDM of VED, together with reviewing the benefit, or lack thereof, of combination VED and thiopurine therapy.

Materials and methods

We performed a comprehensive review of PubMed and Embase from inception through to 1 February 2025. The combination of search terms used included ‘Vedolizumab’, ‘pharmacokinetics’, ‘immunomodulator’, ‘thiopurine’ and ‘combination therapy’. Reference lists of published articles were manually searched to identify additional relevant studies. We included both full-text articles and key abstracts published in English that were relevant to the topic, with the aim of conducting a narrative review.

Studies meeting the following inclusion criteria were included: (1) patients were diagnosed with UC or CD; (2) information on vedolizumab pharmacokinetics and/or immunomodulator co-therapy; (3) studies were original articles. Exclusion criteria were as follows: (1) studies focused on paediatric UC or CD; (2) case reports, case series, review articles, or editorials; and (3) studies in languages other than English. Two reviewers (A.P. and T.C.) independently screened the titles and abstracts of all articles. Disagreements were resolved through discussion, and if consensus was not reached, then a third reviewer (R.W.L.) was consulted. Full-text screening then occurred to determine studies for inclusion. Extracted data included author, year, region, study design, sample size, comparison data, week of assessment and relevant statistics available (odds ratios (ORs) and hazard ratios (HRs)). The methodologic quality and risk of bias were assessed using the Newcastle–Ottawa Scale.¹⁸

Pharmacokinetic role of vedolizumab and TDM

The recommended treatment regimen of VED consists of a 6-week induction phase (weeks 0, 2 and 6) of fixed 300 mg IV infusions, followed by a maintenance phase of 300 mg IV every 8 weeks or 108 mg SC every 2 weeks.^8,9 To address primary non-response and secondary loss of response after fixed dosing administration, numerous studies have investigated the VED exposure–response relationship and the role of TDM.

Trial data

IV administration of vedolizumab

The exposure–efficacy relationships of IV VED from the GEMINI studies examined VED trough concentrations during induction, together with quartile analyses and their associations with clinical outcomes.^8,10 GEMINI 1 and 2 included patients with UC and CD, respectively, who received VED 300 mg IV at weeks 0 and 2, with disease status assessment at week 6. Outcomes analysed included clinical response, clinical remission and mucosal healing. Anti-TNF exposure occurred in 48% of the patients from GEMINI 1, and 62% of patients from GEMINI 2. GEMINI 3 included patients with CD who all had prior anti-TNF exposure and received VED 300 mg IV at weeks 0, 2 and 6.

The analysis from GEMINI 1 by Rosario et al.¹⁹ revealed a positive exposure–efficacy relationship for clinical response, clinical remission and mucosal healing for IV VED induction. A trough concentration increase from quartile 1 (⩽17.1 µg/mL) to quartile 4 (>35.7–140 µg/mL) corresponded to absolute increases of 31% for clinical remission, 34% for clinical response and 43% for mucosal healing at week 6.¹⁹ These findings are supported by higher median VED trough concentrations in UC remitters versus non-remitters (34.7 vs 23.7 µg/mL) at week 6.¹⁹ A propensity-score-based analysis from GEMINI 1 further identified VED trough concentrations of 37.1 µg/mL at week 6, 18.4 µg/mL at week 14 and 12.7 µg/mL during maintenance that were associated with clinical remission.²⁰ In CD, GEMINI 2 demonstrated a modest exposure–efficacy gradient, with a 14% absolute increase in clinical remission from quartile 1 (⩽16.0 µg/mL) to quartile 4 (>33.7–177 µg/mL) at week 6.¹⁹ Like in UC, higher median VED trough concentrations were seen in CD remitters versus non-remitters (26.8 vs 23.5 µg/mL, respectively) at week 6. Possible contributing factors to the lower exposure–efficacy relationship at week 6 in CD versus UC include disease pathophysiology and the time needed to respond to treatment. This interpretation is supported by GEMINI 3, which showed a steeper exposure–efficacy relationship for clinical remission at week 10. The absolute rate increase in clinical remission from quartile 1 to quartile 4 was 22% at week 10 (compared with 14% at week 6).¹⁹

The strength of these analyses is the large, well-conducted randomised controlled trial design, enabling the exploration of drug exposure patterns across multiple clinical and endoscopic outcomes. However, the exposure–efficacy relationships are derived post hoc and cannot establish causality. Furthermore, quartile analyses are broad and may not consider interpatient variability in drug clearance, disease activity and concomitant therapies. Also, although higher concentrations correlated with better outcomes, these studies do not clarify whether proactively targeting particular VED trough concentrations improves outcomes.

Hanzel et al.²¹ aimed to develop a pharmacokinetic–pharmacodynamic model linking VED exposure to endoscopic remission in the LOVE-CD trial. This study provides valuable mechanistic insight, particularly because VED trough concentrations were paired with scheduled endoscopic assessments. Patients received VED 300 mg IV every 8 weeks, and serum concentration measurements were performed before each infusion and at endoscopic assessments at baseline, week 26 and week 52. A VED trough concentration of 20.0 mg/L corresponded to a 35% probability of achieving endoscopic remission. However, the cohort consisted predominantly of patients with refractory CD (89% had prior anti-TNF exposure), which likely reduced overall remission rates and may limit generalisability to biologic-naïve populations. Moreover, dose-optimised regimens were not evaluated, restricting the ability to infer whether higher drug exposure would translate into improved outcomes. Both Hanzel et al.²¹ and Rosario et al.¹⁹ identified low albumin as a predictor of higher VED clearance and reduced probability of remission, reinforcing the relevance of host factors in interpreting VED pharmacokinetics.

Okamoto et al.²² demonstrated that VED pharmacokinetics did not differ between Asian and non-Asian patients with IBD. This is an important finding given that pivotal trials were conducted predominantly in Western populations. Additionally, across multiple analyses, no substantive difference in VED clearance has been observed between UC and CD.^23,24 This suggests that inter-individual rather than disease-specific pharmacokinetic variation is the primary driver of exposure differences.

Maintenance IV VED levels were analysed in the VIEWS trial, which evaluated thiopurine withdrawal for patients with UC receiving IV VED every 8 weeks.²⁵ Patients were in steroid-free clinical remission for at least 6 months, and had a Mayo endoscopic subscore of ⩽1 at baseline. Higher week 48 VED trough concentration levels were associated with clinical remission (16.3 vs 9.2 µg/mL, p = 0.04).²⁶ A week 48 VED trough concentration of 17.7 µg/mL was associated with clinical remission at 2 years, versus 12.4 µg/mL for those not in remission (p = 0.02).²⁶ In quartile analysis, a VED concentration of >11.3 µg/mL was associated with sustained clinical remission at week 48 (AUC 0.71 (95% confidence interval (CI): 0.49–0.93) sensitivity 82.4%, specificity 60.0%).²⁶ Although these results add evidence to potential target concentrations during maintenance therapy, the sample size was modest, and VED trough concentrations were measured in a highly selected population already in deep remission at baseline. Importantly, combination therapy with a thiopurine did not significantly impact VED concentrations (14.7 µg/mL (interquartile rate (IQR), 12.3–18.5 µg/mL) in the combination group vs 15.9 µg/mL (IQR, 10.1–22.7 µg/mL) in the VED monotherapy group, respectively, p = 0.36).²⁵ This is substantiated by Yarur et al. in a prospective cohort study that included 133 patients on VED. The addition of a thiopurine, with 6-TGN levels ⩾152 pmol per 8 × 10⁸ RBCs, did not significantly impact VED trough concentrations (8.8 µg/mL for combination therapy vs 10.5 µg/mL for VED monotherapy, p > 0.05).²⁷

In the ENTERPRISE study, Schwartz et al.²⁸ conducted a randomised controlled trial assessing VED in 32 patients with active perianal fistulising CD. Patients received either standard induction or an additional IV dose at week 10. Although higher VED concentrations were observed from weeks 14 to 30 in the intensified arm, this did not translate into superior clinical outcomes compared to standard dosing (64.3% response in the standard group vs 42.9% in the week 10 group). Notably, the higher concentrations in the intensified group were not consistently maintained, and the small sample size may limit the applicability of these findings.²⁸

Dose-escalation strategies, widely used for anti-TNF agents, have shown mixed results with VED. Outtier et al. performed a multi-centre, prospective study of patients on VED 300 mg IV every 4 weeks undergoing secondary loss of response, and escalated to 4-weekly dosing. Whilst median VED trough concentrations increased from 8.7 to 19.1 µg/mL, clinical response was achieved in 54% of patients at week 8.²⁹ Similarly, a systematic review and meta-analysis by Peyrin-Biroulet et al.³⁰ found that dose escalation restored response in 53.8% of secondary non-responders. These findings suggest that, at least in some patients, higher VED exposure may recapture response. However, the evidence base largely consists of observational cohorts without control groups, and definitions of secondary non-response and clinical remission vary widely between studies.

The recent ENTERPRET study provides an important counterbalance.³¹ It investigated the potential benefit of VED dose-optimisation in patients with UC who had high drug clearance at week 5 and clinical non-response at week 6.³¹ Patients received VED 300 mg IV at weeks 0, 2 and 6, and were then randomised 1:1 to receive standard dosing (300 mg every 8 weeks) or dose-optimised VED (600 mg at week 6, then 300 mg every 4 weeks; or 600 mg at week 6, and then 600 mg every 4 weeks (based on week 5 serum VED concentration)). Clinical remission rates at week 30 were similar between standard dosing and dose-optimised (300 or 600 mg every 4 weeks) patients, despite higher VED trough concentrations in the dose-optimised group.³¹ These results imply that early pharmacokinetic non-response may reflect intrinsic VED non-responsiveness rather than insufficient drug exposure. This suggests there is limited benefit of dose-optimisation in early non-responders with UC.³¹ Notably, ENTERPRET evaluated early non-responders, whereas previous cohort studies focused primarily on secondary non-responders. Therefore, its conclusions may not apply directly to the latter group, and a randomised controlled trial in secondary non-responders would be required to provide definitive evidence regarding the efficacy of dose intensification in this setting.

SC administration of vedolizumab

Similar to GEMINI 1, positive exposure–efficacy outcomes were seen with SC VED from the VISIBILE 1 trial.⁹ After receiving IV VED at week 0 and week 2, patients were randomised to either receive SC VED 108 mg every 2 weeks, IV VED 300 mg every 8 weeks or placebo. Prior anti-TNF exposure occurred in 37.7%, 44.4% and 35.7% of patients in each group, respectively. The primary endpoint was the proportion of patients in clinical remission, defined as a total Mayo score of ⩽2 with no subscore >1 point, at week 52.⁹ Median serum VED trough concentrations were estimated to be higher for SC VED (34.6 µg/mL (90% CI: 15.5–72.8 µg/mL)) than IV VED (11.1 µg/mL (90% CI: 2.1–34.2 µg/mL)), with consistent observed values across study visits.⁹ The proportion of patients who achieved clinical remission at week 52 increased with higher VED exposure. The absolute rate increased from quartile 1 (⩽26.4 µg/mL) to quartile 4 (>44.5 µg/mL) was 33% for clinical remission and 39% for endoscopic improvement.⁹ Positive exposure–efficacy outcomes were also seen with SC VED in CD from the VISIBILE 2 trial.¹¹ In this trial, patients received IV VED at week 0 and week 2, and were then randomised 2:1 to SC VED 108 mg every 2 weeks or placebo. The primary outcome was clinical remission (defined as a Crohn’s disease activity index [CDAI] ⩽150) at week 52. There was an absolute rate increase from quartile 1 (9.2–25.7 µg/mL) to quartile 4 (42.6–131.0 µg/mL) of 13% for clinical remission and 16% for clinical response at week 52.¹¹ This association was less pronounced than in UC.

Real-world data

Several real-world studies have examined the exposure–efficacy relationship of VED in UC and CD, with mixed results. Many have demonstrated a positive association between VED trough concentrations and clinical,^32–36 biochemical,^32,37,38 endoscopic^{21,32,34,39–41} and histological remission.⁴² Factors identified through univariate and multivariate analyses that correlate with higher VED concentrations include smaller body size, less severe disease activity, higher albumin level, lower faecal calprotectin and C-reactive protein levels.^19,21,36,43 Singh et al.⁴⁴ conducted a meta-analysis of five cohort studies, revealing that UC patients who achieve clinical remission have significantly higher vedolizumab trough concentrations during maintenance therapy (14.3 vs 10.5 µg/mL; mean difference 5.1 µg/mL (95% CI: 2.8–7.4), p < 0.01). Similarly, VED trough concentrations were significantly higher in patients achieving endoscopic remission (13.0 vs 9.7 µg/mL; mean difference 5.1 µg/mL (95% CI: 2.2–7.9), p < 0.01). Statistically significant differences were not observed in CD patients.⁴⁴ Overall, Singh et al.⁴⁴ suggested a VED trough concentration of >18–20 µg/mL at week 6 is associated with a higher likelihood of favourable outcomes on follow-up, whilst a maintenance concentration of >10–12 µg/mL is associated with clinical remission. However, the thresholds varied across the studies, which can be attributable to multiple factors such as study design, number of participants, outcome definitions, duration and interval of vedolizumab therapy, previous exposure to biologics (particularly anti-TNF) and assays measuring vedolizumab concentrations.

Consequently, universal cut-off values have not been clearly defined.⁴⁴ It is important to note that while these real-world studies demonstrated dose–response relationships, they do not establish causation. Higher drug concentrations may simply reflect low disease activity, therefore low drug clearance. Notably, the formation of anti-vedolizumab antibodies was low, regardless of vedolizumab trough levels. The studies on 108 mg SC vedolizumab every second week have also shown comparable efficacy to the IV formulation with higher VED trough levels.^36,45

Taken together, these studies highlight important nuances in interpreting VED pharmacokinetics. While higher exposure is associated with better outcomes, particularly in UC, the evidence supporting proactive dose optimisation or routine TDM remains limited. In our view, universal dose-intensification or target-concentration-based dosing is not recommended for all patients. Further controlled studies are needed to clarify which patient subgroups truly benefit from dose escalation and to define clinically actionable concentration thresholds.

Clinical impact of vedolizumab with or without immunomodulators

Combination therapy between a biological agent and an immunomodulator is a potential strategy to improve patient outcomes. With anti-TNF therapy, the addition of an immunomodulator has been shown to improve clinical and endoscopic outcomes whilst reducing the formation of anti-TNF antibodies.^17,46 Prior studies have consistently shown no significant benefit of immunomodulator co-therapy with VED; however, more recent studies suggest a potential therapeutic effect (Table 1).

Table 1.

Studies on vedolizumab and immunomodulator concomitant therapy in patients with inflammatory bowel disease.

Reference	Year	Country of origin	Number of patients	Type of study	Comparison	No. of patients on concomitant IMM	Week of assessment	Statistics	Sustained immunomodulator therapy?
Shelton et al.⁴⁷	2015	USA	UC n = 65 CD n = 107	Multicentre, retrospective study	Concomitant use of immunomodulators and clinical response/remission	CD = 34/107 UC = 17/65	Week 14	OR 0.56 (95% CI: 0.19–1.66) p = 0.30	Unsure whether sustained
Lenti et al.⁴⁸	2018	UK	UC n = 68 CD n = 135	Multicentre, retrospective study	Concomitant use of immunomodulators and clinical response or remission	CD = 70/135 UC = 31/68	Weeks 14 and 52	p = NS	Unsure whether sustained
Stallmach et al.⁴⁹	2016	Germany	UC n = 60 CD n = 67	Multicentre, prospective study	Concomitant use of immunomodulators and clinical remission at week 54	CD: 15/67 – 15% UC: 13/60 – 21.7%	Week 54	UC: 0.2 (CI: 0.02–1.66) p = 0.13 CD: 0.38 (CI: 0.04–3.25) p = 0.37	Unsure whether sustained
Baumgart et al.⁵⁰	2016	Germany	UC n = 115 CD n = 97	Prospective study	Concomitant use of immunomodulators and clinical remission	CD: 78/97 UC: 88/115	Week 14	UC, p = 0.825 CD, p = 0.369	Unsure whether sustained
Kopylov et al.⁵¹	2017	Israel	UC n = 74 CD n = 130	Multicentre, prospective study	Concomitant use of immunomodulators and clinical remission	CD: 32/130 UC: 16/74	Week 14	p = NS	Unsure whether sustained
Samaan et al.⁵²	2017	UK	UC n = 20 CD n = 27 IBD-U n = 3	Multicentre, retrospective study	Proportion of patients on combination therapy vs monotherapy with active disease at initiation of VED who achieved clinical remission	CD + UC = 16/50	Week 14	Combo – 8/16 (50%) vs Mono – 6/21 (29%)	Unsure whether sustained
Eriksson et al.⁵³	2017	Sweden	UC n = 92 CD n = 147 IBD-U n = 7	Multicentre, prospective study	Concomitant use of immunomodulators and drug discontinuation, because of lack of or loss of response		End of follow-up	Adjusted HR 1.39; 95% CI: 0.85–2.30, p = 0.19	Unsure whether sustained
Allegreti et al.⁵⁴	2017	USA	UCn = 40CDn = 96	Multicentre, retrospective study	Concomitant use of an immunomodulator at the initiation of VED and response or remissionInitiation of immunomodulators after initiation of VED and response or remission	Concomitant IMM at induction:–CD: 20/50–UC: 9/46IMM added after induction–CD: 20/50–UC: 3/46	Week 54	UC: OR 1.27, 95% CI: 0.27–5.96CD: OR 1.89, 95% CI: 0.66–5.38UC: OR 0.43; 95% CI: 0.09–2.00CD: OR 8.33; 95% CI: 2.15–32.26	Yes
Amiot et al.⁵⁵	2016	France	UCn = 121CDn = 173	Multicentre, prospective study	Concomitant use of immunomodulators and steroid-free clinical remission	At week 54,CD: 17/78UC: 2/71	Weeks 14 and 54	p = NS	Yes
Hu et al.⁵⁶	2021	USA	UCn = 263CDn = 286	Multicentre, retrospective study	Concomitant use of immunomodulator and clinical response or remission	Concomitant IMM at induction:–CD: 65/286–UC: 66/263	Weeks 30 and 54	CD (OR 1.38, 95% CI: 0.63–3.00) or UC (OR 0.63, 95% CI: 0.33–1.20).	Yes
Kirchgesner et al.⁵⁷	2022	USA and France	UCn = 2176CDn = 1608	Retrospective study	Concomitant use of thiopurine and treatment failure – defined as hospitalisation/surgery, switch to another biologic agent or exposure to systemic steroids	CD: 804UC: 1088	Week 26	Combination therapy CD: RR 0.85, 95% CI: 0.74–0.98)Combination therapy UC: RR 0.90, 95% CI: 0.77–1.05)	Yes
Naganuma et al.⁵⁸	2022	Japan	UCn = 164	Explorative analysis of previous randomised controlled trial	Efficacy of concomitant immunomodulator use in induction and maintenance phase	Concomitant use at weeks 0–10 (UC) – 80/164Concomitant use by week 60 22/41	Weeks 10 and 60	Difference in clinical response, remission and mucosal healing − 0.7 (95% CI: −14.3 to 15.7), 3.3 (95% CI: −8.5 to 15.2) and 1.8 (95% CI: −13 to 6.5)Difference in clinical remission and mucosal healing between subgroups − 26.1 (95% CI: −3.5 to 55.6) and 29.9 (95% CI: 1.4–58.4)	Yes
Jeffrey et al.⁵⁹	2023	Australia	UCn = 61CDn = 24	Single-centre, retrospective cohort study	Concomitant use of immunomodulator (thiopurine or methotrexate) and clinical response	UC: 22/61CD: 7/24	Week 52 (1 year)	No difference in clinical response/remission week 12 (p = 0.38), 26 (p = 0.83) or 52 (p = 0.32)	Yes
Pudipeddi et al.²⁵	2024	Australia	UCn = 62	Randomised controlled trial	Continuing azathioprine vs withdrawing azathioprine and clinical remissionContinuing AZA vs withdrawing AZA and clinical relapseContinuing AZA vs withdrawing AZA and endoscopic remissionContinuing AZA vs withdrawing AZA and histologic remission	UC: 20/62	Week 48	OR 2.5 (95% CI: 0.5–12.7)OR 2.5 (95% CI: 0.5–12.7)OR 3.4 (95% CI: 0.95–12.2), p = 0.05OR 4.2 (95% CI: 1.2–15.2), p = 0.02	Yes

AZA, azathioprine; CD, Crohn’s disease; CI, confidence interval; HR, hazard ratio; IBD, inflammatory bowel disease; IMM, immunomodulator; NS, not significant; OR, odds ratio; RR, relative risk; UC, ulcerative colitis; UK, United Kingdom; USA, United States of America; VED, vedolizumab.

Evidence for combination therapy

Trial data

Recent years have seen more robust studies explore whether combining VED with an immunomodulator offers additional therapeutic benefit. Pudipeddi et al.²⁵ studied the effect of thiopurine withdrawal when used in combination with VED in 62 patients with UC. The primary outcome was VED trough concentration at week 48, which was not significantly different between continued versus withdrawal groups (14.7 µg/mL (IQR, 12.3–18.5 µg/mL) vs 15.9 µg/mL (IQR, 10.1–22.7 µg/mL), respectively, p = 0.36).²⁵ However, thiopurine continuation was associated with higher faecal calprotectin remission (95.0% (19/20) vs 71.4% (30/42), p = 0.03), histologic remission (80.0% (16/20) vs 48.6% (18/37), p = 0.02) and histo-endoscopic remission (75.0% (15/20) vs 32.4% (12/37), p = 0.002).²⁵ No anti-VED antibodies were detected in either group, and hence, the prevention of immunogenicity did not explain the possible thiopurine benefit. Rather, combination therapy with the thiopurine was likely providing an additive immunosuppressive effect. However, these clinical, biochemical and endoscopic outcomes were secondary outcomes in a study primarily powered to assess VED trough concentrations. Thus, the findings should be interpreted cautiously. It should be noted that adverse events were higher in the thiopurine group, mainly relating to mild infections that did not require discontinuation of the thiopurine. Nonetheless, safety considerations are required when using immunomodulator co-therapy given their association with infections, lymphoma and non-melanoma skin cancers.⁶⁰

Naganuma et al.⁵⁸ performed an exploratory analysis of data from a randomised controlled trial studying the efficacy of combination therapy in Japanese patients with moderate to severe UC. Despite lower VED trough concentrations in the combination group, mucosal healing rates at week 60 were significantly higher with combination therapy (77.3% vs 47.4%, difference 29.9% (95% CI: 1.4–58.4)), with a numerical, but not statistically significant, advantage in clinical remission (68.2% vs 42.1%, difference 26.1% (95% CI: −3.5 to 55.6]).⁵⁸ These findings raise the possibility of pharmacodynamic superiority rather than a purely pharmacokinetic effect. However, the study was exploratory, had relatively small group sizes and may not be generalisable beyond the Japanese population. The similar rates of adverse events between groups are reassuring, but longer-term safety remains uncertain.

Real-world data

Two retrospective studies also showed the potential benefit of combination therapy in CD.^54,57 Allegreti et al. assessed clinical response and remission at week 54 after VED initiation.⁵⁴ In patients with CD, the addition of immunomodulators after induction was associated with higher clinical response and remission rates in multivariate analysis (OR: 8.3 (95% CI: 2.2–32.3)).⁵⁴ The authors concluded that adding immunomodulator therapy may represent a salvage therapy for patients demonstrating less than adequate response after induction with VED.⁵⁴ However, these findings are limited by the retrospective design, risk of bias (patients more unwell may have preferentially received combination therapy) and potential confounders. The second study was a retrospective observational review of USA and French healthcare databases comparing the effectiveness of combination therapy with VED and thiopurines against VED monotherapy in patients with CD and UC.⁵⁷ The risk of treatment failure (defined as a composite of hospitalisation or surgery related to IBD, treatment switch to another biological agent or exposure to systemic corticosteroids) was decreased with combination therapy compared with vedolizumab monotherapy in CD (RR: 0.85 (95% CI: 0.74–0.98)) but not in UC (RR: 0.90 (95% CI: 0.77–1.05)).⁵⁷ Although strengthened by a large sample size, the use of administrative coding to define outcomes and medication exposure introduces misclassification risk. Furthermore, prescribing data from the Australian Pharmaceutical Benefits Scheme showed that VED persistence was longer when used as a first-line biological agent in combination with immunomodulators, compared to patients on VED monotherapy (>50.2 vs 40.8 months (95% CI: 10.3–71.3), p = 0.02).⁶¹

To prevent the potential bias inherent in observational studies, Hudesman et al.⁶² compared combination VED and immunomodulator therapy against VED monotherapy by applying propensity score matching. They found that UC and CD patients treated with combination therapy had significantly higher cumulative 12-month rates of clinical remission (47% vs 30%; HR: 4.1 (95% CI: 1.06–15.90) for UC, and 38% vs 32%; HR: 2.3 (95% CI: 1.12–4.74) for CD).⁶² There were numerically but not statistically significant higher rates of endoscopic healing with combination therapy in UC (54% vs 41%; HR: 1.59 (95% CI: 0.37–6.70)) but comparable rates in CD (43% vs 43%; HR: 1.18 (95% CI: 0.45–2.77)).⁶² While propensity matching enhances comparability between groups, the study may not account for variations in thiopurine dosing, adherence or metabolite levels.

Evidence against combination therapy

Trial data

The pivotal GEMINI 1 trial demonstrated the effectiveness of VED in UC.⁸ Of 374 patients randomised to double-blind placebo or VED as induction treatment, 32% were on concomitant immunomodulator therapy. Rates of clinical response, clinical remission and mucosal healing were numerically higher with VED at weeks 6 and 52, irrespective of immunomodulator co-therapy.⁶³ Furthermore, of 368 patients with CD in the GEMINI 2 trial, 34% were on concomitant immunomodulator therapy.⁶⁴ Clinical response and clinical remission were similar for patients on VED, irrespective of immunomodulator use at baseline.⁶⁵ However, these studies were not designed to specifically address the effects of concomitant immunomodulator therapy. Also, concomitant therapy was defined as baseline immunomodulator use; however, patients from the United States had their immunomodulator discontinued at week 6 for patients in the double-blind VED group, or at study entry for open-label VED patients. Nonetheless, there was no significant difference in clinical remission rates between non-US (23.2%) and US (28.9%) patients at week 52.⁶⁵ Additionally, short follow-up for some endpoints reduces the ability to detect differences in outcomes that may require sustained exposure to combination therapy.

Real-world data

Real-world data have also questioned the added value of immunomodulators. A large retrospective study by Hu et al.⁵⁶ with 549 patients examined clinical, endoscopic and persistence outcomes for patients using VED with or without an immunomodulator. There was no difference in clinical response or remission at week 54 in the combination versus monotherapy groups (78.3% vs 72.9%, p = 0.33).⁵⁶ The proportion of patients with endoscopic response or remaining on VED was similar in combination versus monotherapy groups too.⁵⁶ Importantly, propensity-score matching was used to help overcome the limitations of a retrospective analysis with selection bias. Yzet et al.⁶⁶ performed a meta-analysis examining the effects of immunomodulator therapy with VED and ustekinumab. A total of 16 studies were reviewed for the VED analysis on clinical efficacy, and they found that combination therapy was not associated with superior clinical outcomes compared with monotherapy (OR, 0.84; 95% CI: 0.68–1.05).⁶⁶ However, 10 of 16 (62.5%) of these studies only described baseline immunomodulator use at the initiation of VED, and there were no data as to whether patients continued using an immunomodulator throughout the course of VED.⁶⁷ It is unclear whether immunomodulator use was continued in the remaining studies. As such, similar to GEMINI 1, patients may have had their immunomodulator discontinued at an early time point after VED initiation; however, they were still defined in the combination group. This may not reflect true combination therapy. Furthermore, many studies had short follow-up time periods. At least six of the VED studies had a follow-up period of no more than 14 weeks, despite it being unlikely that a benefit of combination therapy would be found with such limited follow-up duration. However, as pointed out by Yzet et al.,⁶⁶ none of the included studies were designed to primarily analyse the benefit of immunomodulator co-therapy with VED.⁶⁷

Future directions

Future work should focus on identifying patient subgroups who would benefit most from VED dose optimisation. Randomised trials specifically targeting secondary non-responders are needed to determine whether dose-escalation improves long-term outcomes, while biomarker and pharmacokinetic/pharmacodynamic-driven approaches may help distinguish mechanistic failure from modifiable underexposure. The role of immunomodulator co-therapy also requires clarification through prospective studies that ensure consistent thiopurine use with analysis of metabolite levels and incorporate robust safety monitoring. As evidence evolves, these efforts will be crucial to guide the rational use of VED TDM, dose escalation and combination therapy in clinical practice.

Conclusion

Overall, the available literature on VED pharmacokinetics and immunomodulator co-therapy is heterogeneous, complex and sometimes contradictory. Despite demonstration of a positive exposure–efficacy relationship of VED in initial clinical trials, a lack of consistent pharmacokinetic results from numerous studies thereafter has limited the utilisation of measuring VED trough concentrations in clinical practice. Furthermore, although combining VED with an immunomodulator does not reduce immunogenicity nor increase VED trough concentrations (like with anti-TNFs), recent higher-quality, yet limited studies suggest that patient outcomes may be improved through an additive immunosuppressive effect. Nonetheless, most of the evidence stems from retrospective observational data, introducing bias and impacting on applicability. Further studies specifically designed to assess clinical, biochemical, endoscopic and histologic outcomes of combination VED and immunomodulator versus VED monotherapy, similar to the SONIC study,³⁶ are required to definitively answer this question.

Footnotes

Acknowledgements

None.

Declarations

ORCID iDs

Aviv Pudipeddi

Thanaboon Chaemsupaphan

Viraj Kariyawasam

Rupert W. Leong

References

Ungaro

Mehandru

Allen

, et al. Ulcerative colitis. Lancet 2017; 389(10080): 1756–1770.

Torres

Mehandru

Colombel

J-F

, et al. Crohn’s disease. Lancet 2017; 389(10080): 1741–1755.

Shi

Hamidi

, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2017; 390(10114): 2769–2778.

Pudipeddi

Liu

Kariyawasam

, et al. Higher prevalence of Crohn disease and ulcerative colitis among older people in Sydney. Med J Aust 2021; 214(8): 365–370.

Wyant

Fedyk

Abhyankar

An overview of the mechanism of action of the monoclonal antibody vedolizumab. J Crohns Colitis 2016; 10(12): 1437–1444.

Kobayashi

Hibi

Improving IBD outcomes in the era of many treatment options. Nat Rev Gastroenterol Hepatol 2023; 20(2): 79–80.

Battat

Dulai

Jairath

, et al. A product review of vedolizumab in inflammatory bowel disease. Hum Vaccin Immunother 2019; 15(10): 2482–2490.

Feagan

Rutgeerts

Sands

, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2013; 369(8): 699–710.

Sandborn

Baert

Danese

, et al. Efficacy and safety of vedolizumab subcutaneous formulation in a randomized controlled trial of patients with ulcerative colitis. Gastroenterology 2020; 158(3): 562–572.e12.

10.

Sandborn

Feagan

Rutgeerts

, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med 2013; 369(8): 711–721.

11.

Vermiere

D’Haens

Baert

, et al. Efficacy and safety of subcutaneous vedolizumab in patients with moderately to severely active Crohn’s disease: results from the VISIBLE 2 randomized trial. J Crohns Colitis 2022; 16(1): 27–38.

12.

Nassar

Cheesbrough

Quraishi

, et al. Proposed pathway for therapeutic drug monitoring and dose escalation of vedolizumab. Frontline Gastroenterol 2022; 13(5): 430–435.

13.

Mitrev

Vande Casteele

Seow

, et al. Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel disease. Aliment Pharmacol Ther 2017; 46(11–12): 1037–1053.

14.

Vermiere

Dreesen

Papamichael

, et al. How, when, and for whom should we perform therapeutic drug monitoring? Clin Gastroenterol Hepatol 2020; 18(6): 1291–1299.

15.

Rodríguez-Moranta

Argüelles-Arias

Del Val

, et al. Therapeutic drug monitoring in inflammatory bowel diseases. Position statement of the Spanish Working Group on Crohn’s Disease and Ulcerative Colitis. Gastroenterol Hepatol 2024; 47(5): 522–552.

16.

Papamichael

Cheifetz

Melmed

, et al. Appropriate therapeutic drug monitoring of biologic agents for patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2019; 17(9): 1655–1668.e3.

17.

Colombel

J-F

Adedokun

Gasink

, et al. Combination therapy with infliximab and azathioprine improves infliximab pharmacokinetic features and efficacy: a post-hoc analysis. Clin Gastroenterol Hepatol 2019; 17(8): 1525–1532.e1.

18.

Wells

Shea

O’Connell

, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses, http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (2011, accessed 02 February 2025).

19.

Rosario

French

Dirks

, et al. Exposure–efficacy relationships for vedolizumab induction therapy in patients with ulcerative colitis or Crohn’s disease. J Crohns Colitis 2017; 11(8): 921–929.

20.

Osterman

Rosario

Lasch

, et al. Vedolizumab exposure levels and clinical outcomes in ulcerative colitis: determining the potential for dose optimization. Aliment Pharmacol Ther 2019; 49(4): 408–418.

21.

Hanzel

Dreesen

Vermiere

, et al. Pharmacokinetic-pharmacodynamic model of vedolizumab for targeting endoscopic remission in patients with Crohn disease: posthoc analysis of the LOVE-CD study. Inflamm Bowel Dis 2021; 28(5): 689–699.

22.

Okamoto

Dirks

Rosario

, et al. Population pharmacokinetics of vedolizumab in Asian and non-Asian patients with ulcerative colitis and Crohn’s disease. Intest Res 2020; 19(1): 95–105.

23.

Rosario

Dirks

Gastonguay

, et al. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn’s disease. Aliment Pharmacol Ther 2015; 42(2): 188–202.

24.

Dreesen

Verstockt

Vermiere

, et al. A population pharmacokinetic model to support therapeutic drug monitoring during vedolizumab therapy. J Crohns Colitis 2019; 13(Suppl. 1): S273–S274.

25.

Pudipeddi

Paramsothy

Kariyawasam

, et al. Effects of thiopurine withdrawal on vedolizumab-treated patients with ulcerative colitis: a randomized controlled trial. Clin Gastroenterol Hepatol 2024; 22(11): 2299–2308.

26.

Chaemsupaphan

Pudipeddi

Lin

H-Y

, et al. Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: the prospective VIEWS pharmacokinetics study. World J Gastroenterol 2025; 31(2): 101292.

27.

Yarur

McGovern

Abreu

, et al. Combination therapy with immunomodulators improves the pharmacokinetics of infliximab but not vedolizumab or Ustekinumab. Clin Gastroenterol Hepatol 2023; 21(11): 2908–2917.

28.

Schwartz

Peyrin-Biroulet

Lasch

, et al. Efficacy and safety of 2 Vedolizumab intravenous regimens for perianal fistulizing Crohn’s disease: ENTERPRISE study. Clin Gastroenterol Hepatol 2022; 20(5): 1059–1067.

29.

Outtier

Wauters

Rahier

J-F

, et al. Effect of vedolizumab dose intensification on serum drug concentrations and regain of response in inflammatory bowel disease patients with secondary loss of response. GastroHep 2021; 3(2): 63–71.

30.

Peyrin-Biroulet

Danese

Argollo

, et al. Loss of response to vedolizumab and ability of dose intensification to restore response in patients with Crohn’s disease or ulcerative colitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2019; 17(5): 838–846.

31.

Jairath

Yarur

Osterman

, et al. ENTERPRET: a randomized controlled trial of vedolizumab dose optimization in patients with ulcerative colitis who have early nonresponse. Clin Gastroenterol Hepatol 2024; 22(5): 1077–1086.

32.

Ungaro

Yarur

Jossen

, et al. Higher trough vedolizumab concentrations during maintenance therapy are associated with corticosteroid-free remission in inflammatory bowel disease. J Crohns Colitis 2019; 13(8): 963–969.

33.

Guidi

Pugliese

Tonucci

, et al. Early vedolizumab trough levels predict treatment persistence over the first year in inflammatory bowel disease. United European Gastroenterol J 2019; 7(9): 1189–1197.

34.

Liefferinckx

Minsart

Cremer

, et al. Early vedolizumab trough levels at induction in inflammatory bowel disease patients with treatment failure during maintenance. Eur J Gastroenterol Hepatol 2019; 31(4): 478–485.

35.

Vande Casteele

Sandborn

Feagan

, et al. Real-world multicentre observational study including population pharmacokinetic modelling to evaluate the exposure–response relationship of vedolizumab in inflammatory bowel disease: ERELATE study. Aliment Pharmacol Ther 2022; 56(3): 463–476.

36.

Steenholdt

Lorentsen

Petersen

, et al. Therapeutic drug monitoring of vedolizumab therapy in inflammatory bowel disease. J Gastroenterol Hepatol 2024; 39(6): 1088–1098.

37.

Al-Bawardy

Ramos

Willrich

MAV

, et al. Vedolizumab drug level correlation with clinical remission, biomarker normalization, and mucosal healing in inflammatory bowel disease. Inflamm Bowel Dis 2019; 25(3): 580–586.

38.

Sivridaş

Creemers

Wong

, et al. Therapeutic drug monitoring of vedolizumab in inflammatory bowel disease patients during maintenance treatment-TUMMY study. Pharmaceutics 2023; 15(3): 972.

39.

Yacoub

Williet

Pouillon

, et al. Early vedolizumab trough levels predict mucosal healing in inflammatory bowel disease: a multicentre prospective observational study. Aliment Pharmacol Ther 2018; 47(7): 906–912.

40.

Yarur

Bruss

Naik

, et al. Vedolizumab concentrations are associated with long-term endoscopic remission in patients with inflammatory bowel diseases. Dig Dis Sci 2019; 64(6): 1651–1659.

41.

Yarur

Deepak

Vande Casteele

, et al. Association between vedolizumab levels, anti-vedolizumab antibodies, and endoscopic healing index in a large population of patients with inflammatory bowel diseases. Dig Dis Sci 2021; 66(10): 3563–3569.

42.

Pouillon

Rousseau

Busby-Venner

, et al. Vedolizumab trough levels and histological healing during maintenance therapy in ulcerative colitis. J Crohns Colitis 2019; 13(8): 970–975.

43.

Dreesen

Verstockt

Bian

, et al. Evidence to support monitoring of vedolizumab trough concentrations in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2018; 16(12): 1937–1946.e8.

44.

Singh

Dulai

Vande Casteele

, et al. Systematic review with meta-analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases. Aliment Pharmacol Ther 2019; 50(8): 848–857.

45.

D’Haens

Rosario

Polhamus

, et al. Exposure–efficacy relationship of vedolizumab subcutaneous and intravenous formulations in Crohn’s disease and ulcerative colitis. Expert Rev Clin Pharmacol 2024; 17(4): 403–412.

46.

Colombel

J-F

Sandborn

Reinisch

, et al. Infliximab, azathioprine or combination therapy for Crohn’s disease. N Engl J Med 2010; 362: 1383–1395.

47.

Shelton

Allegretti

Stevens

, et al. Efficacy of vedolizumab as induction therapy in refractory IBD patients: a multicenter cohort. Inflamm Bowel Dis 2015; 21(12): 2879–2885.

48.

Lenti

Levison

Eliadou

, et al. A real-world, long-term experience on effectiveness and safety of vedolizumab in adult patients with inflammatory bowel disease: the Cross Pennine study. Dig Liver Dis 2018; 50(12): 1299–1304.

49.

Stallmach

Langbein

Atreya

, et al. Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease – a prospective multicenter observational study. Aliment Pharmacol Ther 2016; 44(11–12): 1199–1212.

50.

Baumgart

Bokemayer

Drabik

, et al. Vedolizumab induction therapy for inflammatory bowel disease in clinical practice – a nationwide consecutive German cohort study. Aliment Pharmacol Ther 2016; 43(10): 1090–1102.

51.

Kopylov

Ron

Avni-Biron

, et al. Efficacy and safety of vedolizumab for induction of remission in inflammatory bowel disease – the Israeli real-world experience. Inflamm Bowel Dis 2017; 23(3): 404–408.

52.

Samaan

Pavlidis

Johnston

, et al. Vedolizumab: early experience and medium-term outcomes from two UK tertiary IBD centres. Frontline Gastroenterol 2017; 8(3): 196–202.

53.

Eriksson

Marsal

Bergemalm

, et al. Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBERG). Scand J Gastroenterol 2017; 52(6–7): 722–729.

54.

Allegreti

Barnes

Stevens

, et al. Predictors of clinical response and remission at 1 year among a multicenter cohort of patients with inflammatory bowel disease treated with vedolizumab. Dig Dis Sci 2017; 62(6): 1590–1596.

55.

Amiot

Serrero

Peyrin-Biroulet

, et al. One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicenter cohort study. Aliment Pharmacol Ther 2017; 46(3): 310–321.

56.

Kotze

Burgevin

, et al. Combination therapy does not improve rate of clinical or endoscopic remission in patients with inflammatory bowel disease treated with vedolizumab or ustekinumab. Clin Gastroenterol Hepatol 2021; 19(7): 1366–1376.e2.

57.

Kirchgesner

Desai

Schneeweiss

, et al. Decreased risk of treatment failure with vedolizumab and thiopurines combined compared with vedolizumab monotherapy in Crohn’s disease. Gut 2022; 71(9): 1781–1789.

58.

Naganuma

Watanabe

Motoya

, et al. Potential benefits of immunomodulator use with vedolizumab for maintenance of remission in ulcerative colitis. J Gastroenterol Hepatol 2022; 37(1): 81–88.

59.

Jeffrey

Picardo

Menon

, et al. Combination therapy is not associated with improved rates of clinical or endoscopic remission in patients with inflammatory bowel disease treated with ustekinumab or vedolizumab: a retrospective study. Ann Gastroenterol 2023; 36(4): 430–436.

60.

Singh

Loftus

Jr Limketkai

, et al. AGA living clinical practice guideline on pharmacological management of moderate-to-severe ulcerative colitis. Gastroenterology 2024; 167(7): 1307–1343.

61.

Pudipeddi

Paramsothy

, et al. Vedolizumab has longer persistence than infliximab as a first-line biological agent but not as a second-line biological agent in moderate-to-severe ulcerative colitis: real-world registry data from the Persistence Australian National IBD Cohort (PANIC) study. Ther Adv Gastroenterol 2022; 15: 17562848221080793.

62.

Hudesman

Chang

Shashi

, et al. Impact of concomitant immunomodulator use on vedolizumab effectiveness: a multicentre consortium propensity score-matched analysis. J Crohns Colitis 2018; 12(Suppl. 1): S067–S068.

63.

Colombel

J-F

Loftus

Jr Siegel

, et al. Efficacy of vedolizumab with concomitant corticosteroid or immunomodulator use in patients with ulcerative colitis from GEMINI 1. J Crohns Colitis 2015; 9(Suppl. 1): S296–S297.

64.

Colombel

J-F

Loftus

Jr Siegel

, et al. Efficacy of vedolizumab with concomitant corticosteroid or immunomodulator use in patients with Crohn’s disease from GEMINI 2. J Crohns Colitis 2015; 9(Suppl. 1): S344.

65.

Feagan

Siegel

Melmed

, et al. Efficacy of vedolizumab maintenance therapy with and without combined immunosuppressant use in GEMINI 1 and GEMINI 2. Am J Gastroenterol 2015; 110; S791.

66.

Yzet

Diouf

Singh

, et al. No benefit of concomitant immunomodulator therapy on efficacy of biologics that are not tumor necrosis factor antagonists in patients with inflammatory bowel disease: a meta-analysis. Clin Gastroenterol Hepatol 2021; 19(4): 668–679.

67.

Pudipeddi

Paramsothy

Leong

RW.

Combination therapy of immunomodulators with non-anti-tumor necrosis factor agents in inflammatory bowel disease: need more evidence?

Clin Gastroenterol Hepatol 2022; 20(3): e640–e641.

Vedolizumab in inflammatory bowel disease: pharmacokinetics and the role of immunomodulator co-therapy

Abstract

Plain language summary

Keywords

Introduction

Materials and methods

Pharmacokinetic role of vedolizumab and TDM

Trial data

IV administration of vedolizumab

SC administration of vedolizumab

Real-world data

Clinical impact of vedolizumab with or without immunomodulators

Evidence for combination therapy

Trial data

Real-world data

Evidence against combination therapy

Trial data

Real-world data

Future directions

Conclusion

Footnotes

Acknowledgements

Declarations

ORCID iDs

References