Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies

What is the cardiovascular effect of S1P receptor modulator therapy in multiple sclerosis? Sphingosine 1-phosphate (S1P) receptor (S1PR) modulators are among the most efficient therapies for multiple sclerosis. As small molecules, they are not only acting on the immune but on cardiovascular and nervous systems as well. Short-term effects of S1PR modulators on the cardiovascular system have already been extensively described, while long-term effects are less known. Our review describes the mechanisms of action and the short- and long-term effects of these therapeutic agents on the cardiovascular system in different clinical trials. We systematically reviewed the literature that had been published by January 2022. One hundred seven articles were initially identified by title and abstract using targeted keywords, and thirty-nine articles with relevance to cardiovascular effects of S1PR therapy in multiple sclerosis patients were thereafter considered, including their references for further accurate clarification. Studies on fingolimod, the first S1PR modulator approved for treating multiple sclerosis, primarily support the safety profile of this therapeutic class. The second-generation therapeutic agents along with a different treatment initiation approach helped mitigate several of the cardiovascular adverse effects that had previously been observed at the start of treatment. The heart rate may decrease when initiating S1PR modulators and, less commonly, the atrioventricular conduction may be prolonged, requiring cardiac monitoring for the first 6 h of medication. Continuous therapy with S1PR modulators can increase blood pressure values; therefore, the presence of arterial hypertension should be checked during long-term treatment. Periodic surveillance of the cardiovascular and autonomic functions can help predict cardiac outcomes and prevent possible adverse events in S1PR modulators treatment. Further studies with longer follow-ups are needed, especially for the second-generation of S1PR modulators, to confirm the safety profile of this therapeutic class.

BackgroundEtrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). This post hoc analysis reports the efficacy and safety of etrasimod based on baseline corticosteroid (CS) use in the ELEVATE UC clinical program.MethodsPatients with UC received etrasimod 2 mg or placebo for up to 52 weeks. CS use was permitted; tapering was recommended from Week 12. Efficacy was assessed at Weeks 12 and 52 in ELEVATE UC 52, and Week 12 in ELEVATE UC 12, for patients in the CS and no-CS subgroups. CS-free efficacy at Week 52 was assessed in patients with baseline CS use.ResultsIn ELEVATE UC 52 and ELEVATE UC 12, 93 of 289 (32.2%) and 65 of 238 (27.3%) patients receiving etrasimod and 42 of 144 (29.2%) and 34 of 116 (29.3%) patients receiving placebo, respectively, had concomitant CS use at baseline. In the CS and no-CS subgroups, higher proportions of patients who received etrasimod vs placebo achieved clinical remission (p < 0.05) in ELEVATE UC 52 at Week 12 (CS: 32.3% vs 16.7%; no-CS: 26.0% vs 4.9%) and Week 52 (CS: 31.2% vs 9.5%; no-CS: 33.2% vs 6.9%). In the CS subgroup, significantly more patients receiving etrasimod achieved CS-free clinical remission at Week 52 (31.2% vs 7.1%) compared with those receiving placebo. No increases in infection rates were observed with baseline CS use. Safety was comparable between subgroups.ConclusionsEtrasimod demonstrated efficacy in inducing and maintaining remission in both subgroups. CS-free remission was achieved in the CS subgroup. Safety was consistent, with no increase in infections.Clinical Trial IdentifiersNCT03945188; NCT03996369.

Background Approved treatment options for children and adolescents with ulcerative colitis (UC) are limited.1 The KEPLER phase 3 trial evaluated the efficacy, immunogenicity, pharmacokinetics (PK) and safety of vedolizumab (VDZ), an anti-α4β7 integrin biologic, administered as intravenous (IV) induction and maintenance therapy in children and adolescents with moderately to severely active UC. Methods This phase 3, single arm trial (NCT04779307) enrolled patients with moderate-to-severe UC (modified Mayo score of 5-9 with endoscopic subscore ≥2) aged 2-17 years and weighing ≥10kg with prior failure of conventional therapy such as steroids, immunomodulators, and/or tumour necrosis factor (TNF) antagonists. VDZ IV was administered during a 14-week, open-label induction period followed by a 40-week, randomised, double-blind maintenance period evaluating low- (LD) or high-dose (HD) VDZ (1:1) by body weight (10-15kg [100 vs 150mg]; &amp;gt;15-&amp;lt;30kg [100 vs 200mg]; ≥30kg [150 vs 300mg]) given every 8 weeks. The primary endpoint was clinical remission by modified Mayo score at Week 54 in the intention-to-treat maintenance population. Secondary endpoints included clinical remission at Week 14, sustained clinical remission (at Weeks 14 and 54), corticosteroid-free clinical remission at Week 54, immunogenicity, PK, and safety. Results The trial enrolled 121 patients (10-15kg, n = 3; &amp;gt;15-&amp;lt;30kg, n = 27; ≥30kg, n = 91), of whom 120 were dosed; 93 were subsequently randomised into LD (n = 47) or HD n = 46) groups for maintenance therapy (Table 1). Forty-four of 93 (47.3%) patients achieved the primary endpoint of clinical remission at Week 54, with similar proportions in LD and HD groups (Fig. 1A). Clinical remission rates at Week 54 for patients categorised by weight, age, anti-TNF exposure, and baseline corticosteroid use are shown in Fig. 1B-E. Forty-two of 121 (34.7%) patients achieved clinical remission at Week 14. At Week 54, 27/93 (29.0%) patients achieved sustained clinical remission. Anti-VDZ antibodies occurred in 7/120 (5.8%) VDZ-exposed patients, including neutralizing antibodies in 4 (3.3%); similar VDZ serum trough levels were observed across weight groups. In the safety population, 103/120 (85.8%) patients had treatment emergent adverse events (TEAEs), including 15/120 (12.5%) related to VDZ. Twenty-five of 468 (5.3%) TEAEs were serious. Five (4.2%) patients had serious VDZ-related TEAEs. Seven (5.8%) patients had TEAEs leading to VDZ discontinuation (most common: UC worsening, n = 3; infection, n = 3). Conclusion LD and HD VDZ IV were effective for children and adolescents with UC, including those with prior anti-TNF or corticosteroid failure. Similar rates were observed in adult patients with UC.2 VDZ was well tolerated, with no new safety signals identified.

<h3>Introduction</h3> Mirikizumab (miri) is a humanized, IgG4 monoclonal antibody directed against the p19 subunit of IL-23, a key mediator in the pathogenesis of IBD. We assessed the induction efficacy and...

Ozanimod hydrochloride (Product name: ZEPOZIA® Capsule Starter Pack, ZEPOZIA® Capsules 0.92 mg; Nonproprietary name: ozanimod hydrochloride, hereinafter referred to as ozanimod) is an orally available receptor modulator that acts on the sphingosine 1-phosphate (S1P) receptor and selectively binds with high affinity to S1P1 and S1P5 receptors. Following binding to and activation of S1P1 receptors, ozanimod acts as a functional S1P1 receptor antagonist by inducing internalization of S1P1 receptors expressed on the surface of cells such as lymphocytes through agonism of S1P1 receptors. These effects may ameliorate the pathologic changes of the autoimmune disease ulcerative colitis (UC). The Japanese phase II/III study (Study RPC01-3103) demonstrated the efficacy and safety of this drug in Japanese patients with moderate to severe ulcerative colitis. In Japan, it was approved by the Ministry of Health, Labour and Welfare (MHLW) in December 2024 for the treatment of moderate to severe UC in patients who have had an inadequate response to conventional therapies, and was launched in March 2025. Existing UC treatments show significant therapeutic effects, but medications for moderate to severe UC have respective advantages and disadvantages in efficacy, safety, and administration routes. No treatment meets all criteria. Ozanimod, with a novel mechanism, offers sustained high efficacy in improving clinical symptoms and mucosal damage in moderate to severe UC patients. It has a favorable safety profile, high medication compliance, and is a convenient oral treatment for long-term use. Thus, providing Ozanimod as a new UC treatment option is of high clinical significance.

Background There is an unmet need for novel advanced therapies for patients with mildly to moderately active ulcerative colitis (UC), who are most frequently treated with aminosalicylates, steroids and thiopurines. Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC. This post hoc analysis evaluated the efficacy and safety of etrasimod 2 mg QD vs placebo in a subpopulation of patients from the ELEVATE UC clinical programme with mildly to moderately active UC at baseline, defined as a modified Mayo score (MMS) of 4–6. Methods Data were pooled from the phase 3, randomised, global ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials, and the ELEVATE UC 40 JAPAN (NCT04706793) trial.1,2 This analysis included a subset of the pooled patient population aged ≥18 years who had a baseline MMS of 4–6, including a centrally read endoscopic subscore ≥2 and a rectal bleeding subscore (RBS) ≥1. Efficacy endpoints at Week 12 and Week 52 included clinical remission, endoscopic improvement, symptomatic remission and histologic endoscopic mucosal improvement; at Week 52, sustained clinical remission and corticosteroid (CS)-free clinical remission were assessed. Least squares mean change from baseline in patient-reported outcome 2 (PRO2) score (sum of RBS and stool frequency subscores) was assessed at each visit up to Week 52. Proportions of patients with treatment-emergent adverse events (TEAEs), serious TEAEs and TEAEs leading to discontinuation were assessed. Results In this subgroup analysis, 221 received etrasimod and 109 received placebo. Baseline characteristics were generally balanced between treatment groups; 95 (28.8%) patients were receiving CS at baseline and 241 (73.0%) were biologic/Janus kinase inhibitor naïve. Median baseline MMS was 6.0 in both treatment groups. Significantly greater proportions of patients receiving etrasimod vs placebo achieved all efficacy endpoints at Week 12 and Week 52 (Figure). A significant decrease in PRO2 score for etrasimod vs placebo was observed as early as Week 2 and continued through to Week 32; numerically greater score decreases were observed from Week 36 to Week 52 (Table). Safety was similar between the etrasimod and placebo groups, and consistent with the overall ELEVATE UC population.1 Conclusion Etrasimod demonstrated robust efficacy in clinical, symptomatic and endoscopic endpoints and safety consistent with the overall population in patients with mildly to moderately active UC, as defined by an MMS of 4–6.

Background Filgotinib (FIL) is an oral, once-daily, Janus kinase 1 preferential inhibitor approved for the treatment of adults with moderately to severely active Ulcerative Colitis (UC)1. In the phase 2b/3 SELECTION trial, FIL demonstrated corticosteroid (CS)-sparing effects in patients with UC.2,3 Here, we aimed to characterise real-world systemic CS use in patients with UC receiving FIL. Methods GALOCEAN (NCT05817942) is an ongoing, European, multicentre, prospective, observational study of adults with UC receiving FIL in routine care; this interim analysis reports data up to week (W) 24. Baseline (BL) characteristics, systemic CS use during FIL treatment, and effectiveness outcomes through W24 were analysed for patients receiving FIL with BL CS use (FIL+CS) or without BL CS use (FIL–CS). Effectiveness outcomes assessed at BL, W10 and W24 were the partial Mayo Clinic Score (pMCS), two-item patient-reported outcome (PRO2) score and the proportion of patients in pMCS or PRO2 remission. Results As of 15 January 2025, 353 enrolled patients had BL data; 253 and 164 patients had data at W10 and W24, respectively. At BL, CS use was low; 93 out of 353 patients (26.3%) were in the FIL+CS group and 260 out of 353 patients (73.7%) were in the FIL–CS group. BL characteristics are summarized in Table I. Compared with FIL–CS, the FIL+CS group included a higher proportion of men (66.7% vs 45.8%) and more prior 5-aminosalicylate use (80.6% vs 69.2%), but fewer patients with prior exposure to advanced therapies (54.8% vs 79.6%). In the FIL+CS group, the proportion of patients using CS decreased from BL to 59.4% (41/69 patients) and 46.5% (20/43 patients) at W10 and at W24, respectively. A small number of patients in the FIL–CS group were using CS at W10 (4.4% [8/180] patients) and W24 (3.4% [3/88] patients) (Figure I). Improvements from BL in pMCS and PRO2 score were observed at W10 and W24 in both the FIL+CS and FIL–CS groups (Figure I). In addition, the proportion of patients in pMCS remission increased from 37.5% (24/64 patients) to 45.2% (19/42 patients) in the FIL+CS group and 43.0% (74/172 patients) to 57.6% (53/92 patients) in the FIL–CS group at W10 and W24, respectively. A similar pattern was observed for PRO2 remission (Figure I). Conclusion This real-world analysis showed that in the small number of patients with UC using CS at BL, over half were no longer using CS by W24 after initiating FIL. Patients achieved symptomatic remission and showed improvements in clinical symptoms over time following FIL treatment, irrespective of CS use at BL. These findings support that FIL treatment offers an opportunity for patients to reduce or minimise their CS use, consistent with results from the SELECTION trial.3

Cis-4-methylsphingosine is a sphingosine-1-phosphate receptor modulator

Background Recently, several studies have shown the high efficacy of Indigo naturalis (IN) in the induction therapy for ulcerative colitis (UC). However, the efficacy and safety in the maintenance therapy remain unclear. Thus, we performed this prospective study to investigate the efficacy and safety of IN for induction and maintenance therapy in patients with moderate to severe active UC. Methods We conducted a prospective uncontrolled open-label study at Kyushu university hospital. A total of 33 patients with moderate to severe active UC (clinical activity index (CAI) ≥8) received 2 g per day of IN for 52 weeks. We assessed CAI at week 0, 4, 8, 52, and Mayo endoscopic score (MES) was evaluated at weeks 0, 4, 52. We calculated the clinical remission (CAI ≤4) rate and mucosal healing (MES ≤1) rate at each point. Overall adverse events (AEs) during the follow-up were also estimated. Results Clinical remission rates at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. Mucosal healing rates at weeks 4 and 52 were 48% and 70%. Seventeen patients experienced adverse events (AEs) during the follow-up. Seven severe AEs, including intussusceptions, acute severe colitis, infectious colitis, portal thrombosis, appendicitis, were observed in 4 patients. Conclusion Our prospective study indicated that IN was a promising option for induction and maintenance therapy in UC. However, possible AEs of IN should be paid attention.

The S1P(2) receptor is a member of a family of G protein-coupled receptors that bind the extracellular sphingolipid metabolite sphingosine 1-phosphate with high affinity. The receptor is widely expressed and linked to multiple G protein signaling pathways, but its physiological function has remained elusive. Here we have demonstrated that S1P(2) receptor expression is essential for proper functioning of the auditory and vestibular systems. Auditory brainstem response analysis revealed that S1P(2) receptor-null mice were deaf by one month of age. These null mice exhibited multiple inner ear pathologies. However, some of the earliest cellular lesions in the cochlea were found within the stria vascularis, a barrier epithelium containing the primary vasculature of the inner ear. Between 2 and 4 weeks after birth, the basal and marginal epithelial cell barriers and the capillary bed within the stria vascularis of the S1P(2) receptor-null mice showed markedly disturbed structures. JTE013, an S1P(2) receptor-specific antagonist, blocked the S1P-induced vasoconstriction of the spiral modiolar artery, which supplies blood directly to the stria vascularis and protects its capillary bed from high perfusion pressure. Vascular disturbance within the stria vascularis is a potential mechanism that leads to deafness in the S1P(2) receptor-null mice.

Fingolimod (FTY720) is the first of a new immunomodulator class : sphingosine 1-phosphate (S1P) receptor modulator. We have found FTY720 by chemical modification of a natural product, myriocin derived from Isaria sinclairii, a kind of vegetative wasp. FTY720 has shown to be highly effective in experimental allograft models and autoimmune disease models. A most striking feature of FTY720 is the induction of a marked decrease in peripheral blood lymphocytes at doses that show immunomodulating effects in these models. It is revealed that the reduction of circulating lymphocytes by FTY720 is due to sequestration of lymphocytes into secondary lymphoid organs and thymus. FTY720 is rapidly converted to FTY720-phosphate (FTY720-P) by sphingosine kinases. FTY720-P acts as a potent agonist at S1P receptor type 1 (S1P(1)), internalizes S1P(1) on lymphocytes, and inhibits the migration of lymphocytes toward S1P. Thus, it is highly likely that immunomodulating effects of FTY720 are caused by inhibition of S1P/S1P(1)-dependent lymphocyte egress from secondary lymphoid organs and thymus. Since FTY720 possesses a novel mechanism of action and is reported to be highly effective in multiple sclerosis patients, it is presumed that FTY720 provides a new therapeutic approach for autoimmune diseases including multiple sclerosis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that negatively impacts patients' quality of life. In the last decades, the therapeutic options available for the management of patients with moderate to severe UC have increased significantly, including not only biological drugs but also small molecules. However, there is a persistent need to develop new drugs that act on new targets while minimizing the risk of adverse events. Sphingosine-1-phosphate (S1P) is a membrane-derived lysophospholipid. The S1P gradient between tissues and the circulatory system has a key role in regulating the trafficking of immune cells as autoreactive B and T lymphocytes. S1P receptor modulators could be a safe and efficacious alternative mechanism for reducing inflammation in immune-mediated disorders, including UC, by reducing lymphocyte egress from the lymph nodes to the bloodstream. Several S1P receptor modulators have been developed and tested in UC. Ozanimod is already approved by Food and Drug Administration (FDA) and European Medical Agency (EMA), while etrasimod and VTX002 are still under approval. Oral administration route, rapidity and reliable safety profile are the main advantages of this class of drugs. The aim of this review is to summarize the available evidence for the efficacy, safety, and pharmacokinetics of ozanimod, etrasimod, and VTX002 in UC.

BACKGROUND AND PURPOSEBAF312 is a next-generation sphingosine 1-phosphate (S1P) receptor modulator, selective for S1P1 and S1P5 receptors. S1P1 receptors are essential for lymphocyte egress from lymph nodes and a drug target in immune-mediated diseases. Here, we have characterized the immunomodulatory potential of BAF312 and the S1P receptor-mediated effects on heart rate using preclinical and human data.EXPERIMENTAL APPROACHBAF312 was tested in a rat experimental autoimmune encephalomyelitis (EAE) model. Electrophysiological recordings of G-protein-coupled inwardly rectifying potassium (GIRK) channels were carried out in human atrial myocytes. A Phase I multiple-dose trial studied the pharmacokinetics, pharmacodynamics and safety of BAF312 in 48 healthy subjects.KEY RESULTSBAF312 effectively suppressed EAE in rats by internalizing S1P1 receptors, rendering them insensitive to the egress signal from lymph nodes. In healthy volunteers, BAF312 caused preferential decreases in CD4+ T cells, Tnaïve, Tcentral memory and B cells within 4–6 h. Cell counts returned to normal ranges within a week after stopping treatment, in line with the elimination half-life of BAF312. Despite sparing S1P3 receptors (associated with bradycardia in mice), BAF312 induced rapid, transient (day 1 only) bradycardia in humans. BAF312-mediated activation of GIRK channels in human atrial myocytes can fully explain the bradycardia.CONCLUSION AND IMPLICATIONSThis study illustrates species-specific differences in S1P receptor specificity for first-dose cardiac effects. Based on its profound but rapidly reversible inhibition of lymphocyte trafficking, BAF312 may have potential as a treatment for immune-mediated diseases.

Background Advanced therapies for ulcerative colitis (UC) continue to emerge, creating a complex and growing landscape of treatment options. Afimkibart, a TL1Abinding antibody, demonstrated promising efficacy in TUSCANY-2, a phase 2b trial1. We utilize indirect comparison methods to compare the efficacy of afimkibart versus adalimumab, an anti-TNF therapy, as firstline therapeutics. Methods We performed a post hoc analysis using propensity score (PS) matching across the active arms of TUSCANY2 (NCT04090411) and HIBISCUS I/II (NCT02163759/NCT02171429), two phase 3 trials1,2, to compare the efficacy of afimkibart versus adalimumab among patients who did not previously receive any biologic therapy. Outcomes included clinical remission (defined as stool frequency subscore = 0 or 1; rectal bleeding subscore = 0; and endoscopic subscore = 0 or 1), clinical response, endoscopic improvement, and endoscopic remission after an induction period of 10 or 14 weeks, respectively. PS matching (1:1) adjusted for baseline modified Mayo score, disease duration, baseline corticosteroid use, age, sex, disease extent, and region. Results Patients who met the inclusion criteria for both studies were included in this analysis. In HIBISCUS I/II, 273 patients received adalimumab and 139 received placebo; in TUSCANY2, 101 received afimkibart and 24 received placebo. Before matching, clinical remission rates were 26.0% for adalimumab vs 10.8% for placebo in HIBISCUS I/II, and 41.6% for afimkibart vs 16.7% for placebo in TUSCANY-2. After PS matching, 152 biologicnaïve patients were included in the efficacy comparison. Afimkibart demonstrated significantly greater improvement versus adalimumab (clinical remission risk difference (RD)=19.7% [95% CI 4.9-34.6], endoscopic improvement RD = 26.3% [95% CI 11.2-41.5]) in this population. Findings were directionally consistent across clinical response and endoscopic remission. Results did not change substantively with different covariate sets and model specifications. Conclusion This is the first analysis to use clinical trial data and PS methods to compare the efficacy of afimkibart with other biologics in UC. In the absence of head-to-head trials, we leveraged PS adjustment methods to generate robust comparisons of therapeutic effects, accounting for differences in baseline covariates between trials. It is worth noting that histological and lab data were not included in the PS modeling due to limited availability, and residual confounding by them and other unmeasured factors cannot be entirely ruled out. Overall, afimkibart showed greater improvement across clinical and endoscopic endpoints compared to adalimumab in biologic-naïve patients.

Cellular adhesion molecules play an important role in the pathogenesis of ulcerative colitis, making selective blockade of these molecules a promising therapeutic strategy. Vedolizumab, a recombinant humanized IgG1 monoclonal antibody, inhibits adhesion and migration of leukocytes into the gastrointestinal tract by binding the alpha4beta7 integrin. Animal studies have suggested that vedolizumab may be a useful therapy for ulcerative colitis. This updated systematic review summarizes the current evidence on the use of vedolizumab for induction and maintenance of remission in ulcerative colitis. The primary objectives were to determine the efficacy and safety of vedolizumab used for induction and maintenance of remission in ulcerative colitis. A computer-assisted search for relevant studies (inception to 15 June 2014) was performed using PubMed, MEDLINE, EMBASE and CENTRAL. References from published articles and conference proceedings were searched to identify additional citations. Randomized controlled trials comparing vedolizumab to placebo or a control therapy for induction or maintenance of remission in ulcerative colitis were included. Two authors independently extracted data and assessed the risk of bias for each trial. The primary outcomes were failure to induce clinical remission and relapse. Secondary outcomes included failure to induce a clinical response, failure to induce endoscopic remission, failure to induce an endoscopic response, quality of life, adverse events, serious adverse events and withdrawal due to adverse events. We calculated the relative risk (RR) and 95% confidence intervals (CI) for each outcome. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Four studies (606 patients) were included. All of the studies were rated as having a low risk of bias. Pooled analyses revealed that vedolizumab was significantly superior to placebo for induction of remission, clinical response, and endoscopic remission and prevention of relapse. After 4 to 6 weeks of therapy 77% (293/382) of vedolizumab patients failed to enter clinical remission compared to 92% (205/224) of placebo patients (RR 0.86, 95% CI 0.80 to 0.91; 4 studies 606 patients). After 6 weeks of therapy 48% of vedolizumab patients failed to have a clinical response compared to 72% of placebo patients (RR 0.68, 95% CI 0.59 to 0.78; 3 studies 601 patients). After 4 to 6 weeks of therapy 68% of vedolizumab patients failed to enter endoscopic remission compared to 81% of placebo patients (RR 0.82, 95% CI 0.75 to 0.91; 3 studies, b583 patients). After 52 weeks of therapy, 54% of vedolizumab patients had a clinical relapse compared to 84% of placebo patients (RR 0.67, 95% CI 0.59 to 0.77; 1 study, 373 patients). One small study (28 patients) found no statistically significant difference in endoscopic response (RR 1.00, 95% CI 0.62 to 1.61). GRADE analyses indicated that the overall quality of the evidence for the primary outcomes was high for induction of remission and moderate for relapse (due to sparse data 246 events). There was no statistically significant difference between vedolizumab and placebo in terms of the risk of any adverse event (RR 0.99, 95% CI 0.93 to 1.07), or serious adverse events (RR 1.01, 95% CI 0.72 to 1.42). There was a statistically significant difference in withdrawals due to adverse events. Six per cent of vedolizumab patients withdrew due to an adverse event compared to 11% of placebo patients (RR 0.55, 95% CI 0.35 to 0.87; 2 studies, 941 patients). Adverse events commonly reported across the studies included: worsening ulcerative colitis, headache, nasopharyngitis, upper respiratory tract infection, nausea, and abdominal pain. Moderate to high quality data from four studies shows that vedolizumab is superior to placebo for induction of clinical remission and response and endoscopic remission in patients with moderate to severely active ulcerative colitis and prevention of relapse in patients with quiescent ulcerative colitis. Moderate quality data from one study suggests that vedolizumab is superior to placebo for prevention of relapse in patients with quiescent ulcerative colitis. Adverse events appear to be similar to placebo. Future trials are needed to define the optimal dose, frequency of administration and long-term efficacy and safety of vedolizumab used for induction and maintenance therapy of ulcerative colitis. Vedolizumab should be compared to other currently approved therapies for ulcerative colitis in these trials.