Vedolizumab is approved for the treatment of moderately to severely active Crohn's disease (CD). Real-world evidence is essential for understanding the effectiveness and benefit-risk profile of vedolizumab outside clinical trial settings.

To identify, systematically review and assess the real-world effectiveness and treatment persistence of vedolizumab in patients with CD, particularly over long-term follow-up periods and among populations with differing treatment experience, and to compare with the treatment persistence of anti-tumour necrosis factor (TNF)-α treatment.

Literature searches were conducted to identify studies published from 2014 to 2022. Relevant congress searches were conducted (2015-2022) using Embase or by hand. Data on adults with CD treated with vedolizumab or anti-TNFα treatment in a real-world setting were extracted for meta-analysis.

Data from 73 studies, including 29,894 patients with CD, reported ≥ 1 outcome of interest for this analysis. Vedolizumab treatment persistence rate was 65.3% (95% confidence interval [CI] 60.2-70.1) at 1 year and 54.8% (95% CI 43.9-65.3) at 2 years. The treatment persistence rate with vedolizumab versus anti-TNFα treatment was 84.6% (95% CI 70.2-92.8) versus 75.3% (95% CI 69.7-80.2) at 1 year and 70.6% (95% CI 60.7-78.8) versus 64.6% (95% CI 56.7-71.8) at 2 years. The mucosal healing rate at 1 year was 40.6% (95% CI 34.2-47.3). Clinical remission rates were 39.4% (95% CI 33.9-45.1) at 1 year and 34.3% (95% CI 18.1-55.2) at 2 years. Corticosteroid-free clinical remission rates were 33.2% (95% CI 28.5-38.3) at 1 year and 20.4% (95% CI 12.5-31.5) at 2 years. All clinical outcome rates were higher in biologic-naive than in biologic-experienced patients.

Real-world use of vedolizumab was associated with favourable long-term effectiveness and treatment persistence. Vedolizumab is a suitable first-line biological option for biologic-naive patients with CD.

Vedolizumab (VDZ), a monoclonal antibody to α4β7 integrin, is available for patients with moderate-to-severe ulcerative colitis (UC). This study planned to assess the real-world effectiveness and safety of VDZ for UC patients in Northern China. We enrolled patients with moderate-to-severe UC who underwent VDZ induction therapy from March 2021 to November 2022 at the Affiliated Hospital of Qingdao University. The primary outcome was clinical remission at weeks 14 and 52 after the initial VDZ therapy. Overall adverse events and risk factors associated with loss of response (LOR) were also evaluated. Seventy-three UC patients receiving VDZ therapy were included in this study. The rates of clinical response, clinical remission, and steroid-free clinical remission were 69.9%, 39.7%, and 34.2% at week 14 and 90.5%, 66.7%, and 64.4% at week 52, respectively. The mucosal remission rates were 37.5% (18/48) at week 14 ± 8 and 27.3% (9/33) at week 52 ± 16, while only 2 and 3 patients achieved mucosal healing at weeks 14 ± 8 and 52 ± 16, respectively. Of the UC patients, 23.3% experienced adverse events associated with VDZ, most of which were mild and self-limiting. Until the last follow-up, 37 of 73 UC patients experienced LOR during the maintenance period. Patients with a higher ulcerative colitis endoscopic severity index (UCEIS), partial Mayo scores (PMS), or hemoglobin below 120 g/L at baseline were more likely to experience LOR after VDZ induction therapy. VDZ is an effective and safe agent for patients with moderate-to-severe UC in Northern China. A high baseline UCEIS, PMS, or hemoglobin < 120 g/L may be an independent risk factor for LOR during the maintenance period.

Inflammatory bowel diseases (IBDs) are associated with high healthcare utilization. This systematic review aimed to summarize what is known about the impact of sex, income, and education on the likelihood of bowel surgery, hospitalization, and use of corticosteroids and biologics among patients with IBD.

We used EMBASE, MEDLINE, CINAHL, and Web of Science to perform a systematic literature search. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects meta-analysis for the impact of sex on the likelihood of surgery and hospitalization. In addition, we performed subgroup analyses of the effect of IBD type (Crohn's disease or ulcerative colitis) and age. Finally, meta-regression was undertaken for the year of publication.

In total, 67 studies were included, of which 23 studies were eligible for meta-analysis. In the main meta-analysis, male sex was associated with an increased likelihood of bowel surgery (HR 1.42 (95% CI 1.13;1.78), which was consistent with the subgroup analysis for UC only (HR 1.78, 95% CI 1.16; 2.72). Sex did not impact the likelihood of hospitalization (OR 1.05 (95% CI 0.86;1.30), although the subgroup analysis revealed an increased likelihood of hospitalization in CD patients (OR 1.42, 95% CI 1.28;1.58). In 9 of 10 studies, no significant sex-based differences in the use of biologics were reported, although in 6 of 6 studies, female patients had lower adherence to biologics. In 11 of 13 studies, no significant sex-based difference in the use of corticosteroids was reported. The evidence of the impact of income and education on healthcare utilization was sparse and pointed in different directions. The substantial heterogeneity between studies was explained, in part, by differences in IBD type and age.

The results of this systematic review indicate that male patients with IBD are significantly more likely to have surgery than female patients with IBD but are not, overall, more likely to be hospitalized, whereas female patients appear to have statistically significantly lower adherence to biologics compared to male patients. Thus, clinicians should not underestimate the impact of sex on healthcare utilization. Evidence for income- and education-based differences remains sparse.

PROSPERO CRD42022315788.

Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease. Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients. However, issues of primary non-response (PNR) and secondary loss of response (SLOR) to non-tumour necrosis factor inhibitor (TNFi) therapies remains a common problem. Specific issues include the choice of optimization of therapy, identifying when dose optimization will recapture response, establishing optimal dose for escalation and when to switch therapy.

To explores the issues of PNR and SLOR to non-TNFi therapies.

This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR. It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring (TDM).

In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin (IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response. For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.

The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.

Real-world data on starting intravenous (IV) vedolizumab (VDZ) and transitioning to subcutaneous (SC) treatment in inflammatory bowel disease (IBD) are scarce.

To assess treatment outcomes of patients with IBD starting IV VDZ and switching to SC VDZ in routine clinical care.

Adult patients with IBD switching from IV to SC VDZ treatment between 1 March 2020 and 31 December 2021 were identified from the Swedish IBD quality register. The primary outcome was SC VDZ persistence. Secondary outcomes included clinical remission, changes in quality of life (QoL) according to EuroQual 5-Dimensions 5-Levels (EQ-5D-5L) and the Short-Health Scale (SHS) and inflammatory markers, including faecal Calprotectin (FCP).

Altogether, 406 patients with IBD (Crohn's disease, n = 181; ulcerative colitis, n = 225) were identified. After a median follow-up of 30 months from starting IV VDZ treatment, the persistence rates were 98%(178/181) in Crohn's disease and 94% (211/225) in ulcerative colitis. Most patients (84%) transitioned during maintenance therapy, and the median follow-up from switch to SC VDZ was 10 months. Compared to baseline, statistically significant improvements were observed in all domains of the SHS, EQ-5D index value and visual analogue scale. Median (interquartile range) FCP concentrations (μg/g) decreased from 459 (185-1001) to 65 (26-227) in Crohn's disease (n = 45; p < 0.001) and from 646 (152-1450) to 49 (20-275) in ulcerative colitis (n = 58; p < 0.001).

Initiating IV VDZ and switching to SC treatment was associated with high persistence rates and improvements in measures of QoL and FCP. These findings are reassuring for patients who start IV VDZ and switch to SC VDZ.

Vedolizumab is a first-line treatment option for ulcerative colitis. There are differences in incidence of ulcerative colitis between males and females, but whether sex affects treatment outcomes is less clear. We examined sex-based differences in patients with ulcerative colitis initiated on vedolizumab from two major randomized controlled trials (RCTs). We conducted a post-hoc analysis on participants with ulcerative colitis from the VARSITY and GEMINI-1 RCTs who received vedolizumab. Outcomes of interest were rates of clinical improvement, clinical remission, and endoscopic improvement at weeks 6, 14, and 52 in male and female participants, as were differences in concentrations of trough vedolizumab and C-reactive protein; 1009 persons in GEMINI-1 and VARSITY trials were included. Male and female patients had similar disease characteristics aside from males being more likely to have Mayo 3 grade endoscopic severity at baseline (62.8 vs. 48.9%, P  < 0.001). At week 6, females were more likely to have endoscopic improvement (47.4 vs. 35.2%, P  = 0.001) and increased vedolizumab trough levels [34.0 (23.0-44.5) vs. 28.9 (19.0-34.6), P  < 0.001]. The probability of achieving clinical remission (28.9 vs. 34.5%, P  = 0.057) or endoscopic improvement (35.5 vs. 39.3%, P  = 0.212) at week 52 was not different between males and females. Females with ulcerative colitis treated with vedolizumab appear more likely to achieve early endoscopic improvement than males, though longer-term outcomes demonstrated no difference. Further studies are required to better understand mechanisms through which sex or sex-associated factors could influence response to therapy in ulcerative colitis.

Background and Objectives: The subcutaneous (SC) formulation of vedolizumab has proven to be effective for the maintenance of remission after intravenous induction. Little is known about the efficacy of switching from intravenous maintenance treatment to SC. We aimed to assess the real-world efficacy of switching to SC treatment and to assess the impact of a baseline treatment regimen. Materials and Methods: In this observational cohort study, adult patients with inflammatory bowel disease who were switched to SC vedolizumab maintenance treatment were enrolled. Patients after intravenous induction and patients who switched from intravenous maintenance treatment (every 8 weeks or every 4 weeks) were included. The SC vedolizumab dosing was 108 mg every 2 weeks, regardless of the previous regimen. The clinical, biochemical, and endoscopic disease activity parameters and vedolizumab serum concentrations at the time of the switch and at the follow-up were assessed. Results: In total, 135 patients (38% Crohn's disease, 62% ulcerative colitis) were switched to SC vedolizumab treatment. The median time to the first follow-up (FU) was 14.5 weeks (IQR 12-26), and the median time to the second FU was 40 weeks (IQR 36-52). Nine patients (7%) discontinued SC vedolizumab treatment, with two-thirds of them discontinuing due to active disease. In all dosing regimens, there were no significant changes in the clinical scores and CRP at the baseline and first and second FUs. Clinical and biochemical remission appeared to be maintained irrespective of the previous dosing regimen. Conclusions: The results of this real-world study suggest that the maintenance of clinical and biomarker remission can be achieved in patients who switched from intravenous to SC vedolizumab. The baseline vedolizumab dosing regimen (every 4 weeks versus every 8 weeks) did not have an impact on outcomes.

Sex (the physical and physiologic effects resulting from having specific combinations of sex chromosomes) and gender (sex-associated behaviours, expectations, identities, and roles) significantly affect the course of inflammatory bowel disease (IBD) and the experience of living with IBD. Sex-influenced physiologic states, like puberty, the menstrual cycle, pregnancy, and andropause/menopause may also impact and be impacted by IBD. While neither Crohn's disease nor ulcerative colitis is commonly considered sex-determined illnesses, the relative incidence of Crohn's disease and ulcerative colitis between males and females varies over the life cycle. In terms of gender, women tend to use healthcare resources at slightly higher rates than men and are more likely to have fragmented care. Women are more commonly prescribed opioid medications and are less likely than men to undergo colectomy. Women tend to report lower quality of life and have higher indirect costs due to higher rates of disability. Women are also more likely to take on caregiver roles for children with IBD. Women with IBD are more commonly burdened with adverse mental health concerns and having poor mental health has a more profound impact on women than men. Pregnant people with active IBD have higher rates of adverse outcomes in pregnancy, made worse in regions with poor access to IBD specialist care. The majority of individuals with IBD in Canada do not have access to a pregnancy-in-IBD specialist; access to this type of care has been shown to allay fears and increase knowledge among pregnant people with IBD.

Many observational studies on the use of vedolizumab [VDZ] in patients with Crohn's disease [CD] and ulcerative colitis [UC] have been published in the past few years. We aimed to comprehensively summarise its effectiveness and safety by pooling data only from observational studies.

PubMed/Medline and Embase were systematically searched for observational studies on patients with CD and UC treated with VDZ through December 2021. The rates of clinical remission and overall adverse events were the primary outcomes. The rates of steroid-free clinical remission, clinical response, mucosal healing, C-reactive protein normalisation, loss of response, VDZ dose escalation, colectomy, serious adverse events, infections, and malignancies were considered as secondary outcomes.

In all, 88 studies comprising 25 678 patients [13 663 with CD and 12 015 with UC] met the inclusion criteria. In patients with CD, the pooled estimate rates of clinical remission were 36% at induction and 39% at maintenance. In patients with UC, the pooled estimate rates of clinical remission were 40% at induction and 45% at maintenance. The pooled estimate of incidence rate of adverse events was 34.6 per 100 person-years. At multivariable meta-regression analysis, studies with increased male proportion were independently associated with higher rates of clinical remission and steroid-free clinical remission at both induction and maintenance, and clinical response at maintenance in patients with CD. Studies with increased disease duration were independently associated with higher mucosal healing rates at maintenance in patients with UC.

Observational studies demonstrated extensively the effectiveness of VDZ, with a reassuring safety profile.

Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and inflammatory bowel disease in general. This systematic review and meta-analysis summarises the current evidence of vedolizumab in the induction and maintenance of remission in Crohn's disease.

To evaluate the benefits and harms of vedolizumab versus placebo for the induction and maintenance of remission in people with Crohn's disease.

We used standard, extensive Cochrane search methods. The latest search date was 30 November 2022.

We included randomised controlled trials (RCTs) and quasi-RCTs comparing vedolizumab to placebo for the induction or maintenance of remission in people with Crohn's disease.

We used standard Cochrane methods. For induction studies, the primary outcome was 1. clinical remission, and secondary outcomes were rates of 2. clinical response, 3. adverse events, 4. serious adverse events, 5. surgery, 6. endoscopic remission and 7. endoscopic response. For maintenance studies, the primary outcome was 1. maintenance of clinical remission, and secondary outcomes were rates of 2. adverse events, 3. serious adverse events, 4. surgery, 5. endoscopic remission and 6. endoscopic response. We used GRADE to assess certainty of evidence.

We analysed induction (4 trials, 1126 participants) and maintenance (3 trials, 894 participants) studies representing people across North America, Europe, Asia and Australasia separately. One maintenance trial administered subcutaneous vedolizumab whilst the other studies used the intravenous form. The mean age ranged between 32.6 and 38.6 years. Vedolizumab was superior to placebo for the induction of clinical remission (71 more per 1000 with clinical remission with vedolizumab; risk ratio (RR) 1.61, 95% confidence interval (CI) 1.20 to 2.17; number needed to treat for an additional beneficial outcome (NNTB) 13; 4 studies; high-certainty evidence) and superior to placebo for inducing clinical response (105 more per 1000 with clinical response with vedolizumab; RR 1.43, 95% CI 1.19 to 1.71; NNTB 8; 4 studies; high-certainty evidence). For the induction phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (9 fewer serious adverse events per 1000 with vedolizumab; RR 0.91, 95% CI 0.62 to 1.33; 4 studies; low-certainty evidence) and probably equivalent to placebo for overall adverse events (6 fewer adverse events per 1000 with vedolizumab; RR 1.01, 95% CI 0.93 to 1.11; 4 studies; moderate-certainty evidence). Vedolizumab was superior to placebo for the maintenance of clinical remission (141 more per 1000 with maintenance of clinical remission with vedolizumab; RR 1.52, 95% CI 1.24 to 1.87; NNTB 7; 3 studies; high-certainty evidence). During the maintenance phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (3 fewer serious adverse events per 1000 with vedolizumab; RR 0.98, 95% CI 0.68 to 1.39; 3 studies; low-certainty evidence) and probably equivalent to placebo for the development of overall adverse events (0 difference in adverse events per 1000; RR 1.00, 95% CI 0.94 to 1.07; 3 studies; moderate-certainty evidence).

High-certainty data across four induction and three maintenance trials demonstrate that vedolizumab is superior to placebo in the induction and maintenance of remission in Crohn's disease. Overall adverse events are probably similar and serious adverse events may be similar between vedolizumab and placebo during both induction and maintenance phases of treatment. Head-to-head research comparing the efficacy and safety of vedolizumab to other biological therapies is required.

Factors related to patient diversity may play a major role in the pathogenesis and clinical manifestation of intestinal and liver diseases and should be considered during diagnostic workup and therapeutic decisions. Here we discuss how diversity factors such as gender, ethnicity, age and socioeconomic parameters may affect the manifestation and disease course of inflammatory bowel diseases (IBD, i.e. Crohn's disease and ulcerative colitis). Consideration of such factors may help to pave the path towards personalized medicine approaches in clinical practice.

Vedolizumab is a gut-selective anti-lymphocyte trafficking agent used to treat ulcerative colitis (UC) and Crohn's disease.

We aimed to evaluate the effectiveness, safety, and durability of the therapeutic effect of vedolizumab after treatment discontinuation in a real-world cohort of patients with UC treated in Poland.

This was a multicenter, prospective study involving patients with moderate to severely active UC from 12 centers in Poland who qualified for reimbursed treatment with vedolizumab between February and November 2019.

The primary endpoints were clinical response (⩾2-point improvement from baseline on partial Mayo score) and clinical remission (partial Mayo score 0-1), including steroid-free remission, at week 54. Other outcomes included response durability at 26 weeks after treatment discontinuation, identification of predictors of response and remission, and safety assessment.

In all, 100 patients with UC were enrolled (55 biologic naïve and 45 biologic exposed). At baseline, 68% of patients were on corticosteroids and 45% on immunomodulators. Clinical response was observed in 62% of patients, clinical remission in 50%, and steroid-free remission in 42.6% at week 54. Within 26 weeks after treatment discontinuation, 37% of patients who maintained response by week 54 relapsed. The decreased number of liquid stools and rectal bleeding and endoscopic response at week 14 were predictive factors for response at week 54. Time from diagnosis ranging 2-5 years, decreased stool frequency, and non-concomitant use of corticosteroids at baseline and at week 14 were predictive factors for remission at week 54. Partial Mayo score < 3 with no subscale score > 1 at week 54 was a predictive factor for durable response after treatment discontinuation. The rate of serious adverse events related to treatment was 3.63 per 100 patient-years.

Vedolizumab is effective and safe in UC treatment in Polish patients. However, the relapse rate after the treatment cessation was high.

ENCePP (EUPAS34119).

Inflammatory bowel diseases in children are characterized by a wide variety of symptoms and often a severe clinical course. In the treatment, we aimed to induce and maintain remission. We focused on assessing the efficacy and safety of the concomitant use of two biologic therapies including: anti-TNF (infliximab, adalimumab) vedolizumab and ustekinumab in a refractory pediatric IBD cohort.

Fourteen children (nine ulcerative colitis, one ulcerative colitis/IBD-unspecified, four Crohn's disease) with a disease duration of 5.2 (8 months-14 years) years, initiated dual therapy at an age of 11.7 (3-17) years after failure of monotherapy with a biological drug. Five patients (36%) were treated with vedolizumab/adalimumab (VDZ + ADA), five (36%) with ustekinumab/adalimumab (UST + ADA), and three (21%) with infliximab/vedolizumab (IFX + VDZ). One patient (7%) was switched from a combination of vedolizumab and adalimumab to ustekinumab and adalimumab during follow-up.

A clinical improvement was obtained in ten children (73%; 5 UC, 1 UC/IBD-unspecified, 4 CD) on the PCDAI/PUCAI scale after 4 months of a second biological drug being added. The median fecal calprotectin decreased from 1610 µg/g (140-10,100) to 586 µg/g (5-3410; p = 0.028) between baseline and 4 months.

Our clinical experience suggests that dual therapy may be an option for pediatric patients with moderate and severe courses of IBD with limited therapeutic options.

Inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract, is a global health care problem. Compelling evidence shows sex differences regarding the prevalence, pathophysiology, clinical presentation, and treatment outcome of IBD. Sex hormones, including estrogen, progesterone, and androgen, have been proposed to have a role in the pathogenesis of sexual dimorphism in IBD. Clinical and experimental data support the modulatory effects of sex hormones on various clinical characteristics of the disease, including intestinal barrier dysfunction and mucosal immune activation. Additionally, the potential role of sex hormones in the modulation of gut microbiota is attracting increasing attention. Here, we discuss the sex dimorphic disease profile and address the potential mechanisms involved in the sex-specific pathogenesis of IBD. Improved understanding of these sex differences in the clinic could improve the knowledge of patients with IBD with heterogeneous disease profiles.

Subcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions.

To assess the effectiveness, safety and pharmacokinetics of a switch from intravenous (IV) to SC maintenance vedolizumab in patients with IBD METHODS: In this prospective cohort study, patients with IBD who had ≥4 months IV vedolizumab were switched to SC vedolizumab. We studied the time to discontinuation of SC vedolizumab, adverse events (AEs), changes in clinical and biochemical outcomes and vedolizumab concentrations at baseline, and weeks 12 and 24.

We included 82 patients with Crohn's disease (CD) and 53 with ulcerative colitis (UC). Eleven (13.4%) patients with CD and five (9.4%) with UC discontinued SC vedolizumab after a median of 18 (IQR 8-22) and 6 weeks (IQR 5-10), respectively. Four patients with CD switched to a different drug due to loss of response, nine switched back to IV vedolizumab due to adverse events, and three due to needle fear. Common AEs were injection site reactions (n = 15) and headache (n = 6). Median clinical and biochemical disease activity remained stable after the switch. Median serum vedolizumab concentrations increased from 19 μg/ml at the time of the switch to 31 μg/ml 12 weeks after the switch (p < 0.005).

Switching from IV to SC vedolizumab maintenance treatment is effective in patients with CD or UC. However, 9% of patients were switched back to IV vedolizumab due to adverse events or fear of needles.

Sex and gender refer to biological and social differences between men and women. While well-evaluated in other disciplines, their roles in inflammatory bowel disease (IBD) are not well-defined. This study aimed to characterize differences in healthcare outcomes in men and women with IBD.

A retrospective single-centre cohort study was conducted to evaluate differences between men and women receiving care for Crohn's disease (CD) and ulcerative colitis (UC) at the Western University Personalized Medicine Clinic from March 2012 to September 2019. The primary endpoint was the proportion of IBD drugs used for all drug classes. Additional outcomes in healthcare utilization and disease phenotype were assessed. Student's t test and Fisher's exact test were used to assess differences RESULTS: A total of 1015 participants were included (CD = 656; UC = 359). In UC and CD, 47.9% and 59.0% were women, respectively. Overall, women were more likely prescribed budesonide than men (23.6% vs. 13.4%; p < 0.0001), while more men were exposed to prednisone for IBD management (73.5% vs. 67.4%; p = 0.04). Immunomodulator use was higher in men with CD versus women (86.6% vs. 78.3%; p = 0.008) and of those exposed, women more commonly experienced ADRs (29.5% vs. 21.2%; p = 0.01). Though no sex-related difference was identified, age was a predictor of biologic exposure in women with CD and men with UC, with those > 55 being less likely to receive biologics.

These findings highlight differences in disease course and treatment approaches between men and women with IBD and support the consideration of sex and gender when researching disease outcomes.

Real-world data on clinical outcomes of ustekinumab in ulcerative colitis are lacking.

To assess short- and long-term clinical outcomes of ustekinumab in ulcerative colitis.

Adult ulcerative colitis patients without previous colectomy starting ustekinumab treatment up until 11 December 2020 were identified through the Swedish Inflammatory Bowel Disease Register (SWIBREG). Prospectively recorded data were extracted from the SWIBREG. The primary outcome was persistence to ustekinumab 16 weeks after treatment initiation. Secondary outcomes included drug persistence beyond week 16, clinical remission (defined as a patient-reported Mayo rectal bleeding subscore = 0 and stool frequency subscore ≤1), biochemical remission (defined as faecal-calprotectin <250 μg/g) and changes in health-related quality of life (HRQoL), as measured by the Short Health Scale (SHS). Logistic regression was used to identify potential predictors of ustekinumab persistence at 16 weeks.

Of the 133 patients with ulcerative colitis, only three were naïve to biologics and tofacitinib. The persistence rates of ustekinumab were 115/133 (86%) at 16 weeks and 89/133 (67%) at last follow-up, that is, after a median follow-up of 32 (interquartile range 19-56) weeks. The clinical remission rates were 17% at 16 weeks and 32% at the last follow-up. The corresponding rates for biochemical remission were 14% and 23%. The median faecal-calprotectin concentration decreased from 740 μg/g at baseline to 98 μg/g at the last follow-up (p < 0.01, n = 37). Improvement was seen in each dimension of the SHS between baseline and last follow-up (p < 0.01 for each dimension, n = 46). Male sex was associated with ustekinumab persistence at 16 weeks (adjusted odds ratio = 4.00, 95% confidence interval: 1.35-11.83).

In this nationwide real-world cohort of ulcerative colitis patients with prior drug failures, including other biologics and tofacitinib, ustekinumab was associated with high drug persistence rates and improvements in clinical, biochemical and HRQoL measures.

Vedolizumab is a gut-selective treatment approved for Crohn's disease (CD) and ulcerative colitis (UC). Recently, a subcutaneous formulation of vedolizumab was approved. The aims of this study were to evaluate efficacy, safety, pharmacokinetics, patient experience and costs following a switch from intravenous to subcutaneous vedolizumab treatment.

Patients were switched from intravenous to subcutaneous vedolizumab maintenance treatment and followed prospectively for 6 months and a subgroup for 12 months. The primary endpoint was change in faecal calprotectin levels. Furthermore, we evaluated clinical disease activity, remission rates, plasma CRP, drug persistence, adverse events, local injection reactions, serum drug concentrations, patient satisfaction, quality-of-life and treatment costs.

Eighty-nine patients were included (48 CD; 41 UC). Faecal calprotectin decreased significantly in CD but not in UC. Clinical indices, remission rates, plasma CRP levels and quality-of-life scores remained unchanged. Patients that had been on standard compared to optimised IV vedolizumab dosing displayed similar outcomes on standard SC dosing. Drug persistence at 6 and 12 months was 95.5% and 88.5%, respectively. Frequencies of adverse events were similar before and after the switch. No serious adverse events occurred. Transient severe local injection reactions were experienced by 1.2% of patients. Median vedolizumab trough levels were 2.3 times higher on subcutaneous compared to intravenous treatment. Patient satisfaction was generally high. Annualised treatment costs were reduced by 15% following the switch.

The switch from intravenous to subcutaneous vedolizumab could be done with preserved therapeutic effectiveness, safety, high patient satisfaction and low discontinuation rate, at a reduced cost.

Methotrexate (MTX) is included in the therapeutic armamentarium of Crohn's disease (CD), although its positioning is currently uncertain in an era in which many effective biological drugs are available. No systematic reviews or meta-analysis have stratified the clinical outcomes of MTX according to the specific clinical scenarios of its use.

Medline, PubMed and Scopus were used to extract eligible studies, from database inception to May 2021. A total of 163 studies were included. A systematic review was performed by stratifying the outcomes of MTX according to formulation, clinical indication and criteria of efficacy.

The use of MTX is supported by randomized clinical trials only in steroid-dependent CD, with similar outcomes to thiopurines. The use of MTX in patients with steroid-refractoriness, failure of thiopurines or in combination with biologics is not supported by high levels of evidence. Combination therapy with biologics can optimize the immunogenic profile of the biological drug, but the impact on long-term clinical outcomes is described only in small series with anti-TNFα. Other off-label uses, such as fistulizing disease, mucosal healing, postoperative prevention and extraintestinal manifestations, are described in small uncontrolled series. The best performance in most indications was shown by parenteral MTX, favouring higher doses (25 mg/week) in the induction phase.

Evidence from high-quality studies in favour of MTX is scarce and limited to the steroid-dependent disease, in which other drugs are the leading players today. Many limitations on study design have been found, such as the prevalence of retrospective underpowered studies and the lack of stratification of outcomes according to specific types of patients and formulations of MTX.

MTX is a valid option as steroid-sparing agent in steroid-dependent CD. Numerous other clinical scenarios require well-designed clinical studies in terms of patient profile, drug formulation and dosage, and criteria of efficacy.

Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy.

We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes.

Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response.

We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes.

Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.

We investigated the real-life effectiveness and safety of vedolizumab (VDZ) induction therapy among Korean patients with Crohn disease (CD) or ulcerative colitis (UC) for whom anti-tumor necrosis factor therapy previously failed.

Adult patients who started VDZ induction therapy at 16 centers were prospectively enrolled in the Korean VDZ nationwide registry. The coprimary outcomes were clinical remission, defined as a Crohn's Disease Activity Index score <150 points and a partial Mayo score ≤2 points with a combined rectal bleeding and stool frequency subscore ≤1 point at week 14 and endoscopic remission defined as a Mayo endoscopic subscore ≤1 point. We also analyzed predictors of clinical remission.

Between August 2017 and November 2019, a total of 158 patients (80 with CD and 78 with UC) received VDZ induction therapy. Clinical remission rates among patients with CD and patients with UC were 44.1% and 44.0%, respectively. Among patients with UC, the endoscopic remission rate was 32.4%. Clinical response and remission rates showed increasing trends during induction therapy. Multivariable analysis revealed that clinical response at week 6 was the only predictor of clinical remission at week 14 for both patients with CD and patients with UC. Among patients who experienced 1 or more adverse events (n = 71; 44.9%), disease exacerbation (n = 28; 17.7%) was the most common adverse event.

Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy.

Clinical trials demonstrated that golimumab is effective in anti-TNF naïve patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting.

This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore ≥2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by ≥3 points or 30% from baseline) and remission (defined as a Mayo score of ≤2 with no individual subscores >1).

Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6-9) at baseline to 1 (0-5) at 52 weeks (p < .01) and the faecal calprotectin decreased from 862 (335-1759) µg/g to 90 (34-169) µg/g (p < .01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5‒1188.9).

The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis.

Vedolizumab, a humanized antibody targeting the α₄β₇ integrin, was proven to be effective in the treatment of moderate-to-severe ulcerative colitis (UC) in randomized clinical trials. The aim of the POLONEZ study is to determine the demographic and clinical characteristics of the patients with UC treated with vedolizumab within the scope of the National Drug Program in Poland and to assess the real-world effectiveness and safety of vedolizumab in the study population. Here we report the demographic and clinical characteristics of these patients.

This prospective study included adult patients eligible for UC treatment with vedolizumab who were recruited from 12 centers in Poland between February and November 2019. Collected data included sex, age, disease duration, presence of extraintestinal manifestations or comorbidities, status of previous biologic treatment, and current concomitant treatment. Disease extent was determined according to the Montreal classification, and disease activity was measured with the Mayo Score.

A total of 100 (55 biologic-naïve and 45 biologic-exposed) patients were enrolled in the study (51% female, median age 35 years). Among biologic-exposed patients (mostly infliximab-treated), 57% had failed to respond to the therapy. The disease duration was significantly shorter in biologic-naïve (median 5 years) than in biologic-exposed (8 years, p = 0.004) or biofailure patients (7 years, p = 0.04). In the overall population the median Total Mayo Score was 10. Disease extent and activity were similar between the subgroups.

Our study indicates that patients treated with vedolizumab in Poland receive the drug relatively early after UC diagnosis, but their disease is advanced. More than half of the patients had not been treated with biologic drugs before initiating vedolizumab. The study was registered in ENCePP database (EUPAS34119).

Characteristics of patients treated for ulcerative colitis with vedolizumab in Poland Treatment of moderate-to-severe ulcerative colitis (UC) with the integrin antagonist vedolizumab became available within the Polish National Drug Program (NDP) in 2018. In this study, for the first time, we provide detailed demographic and clinical characteristics of 100 patients (median age 35 years, 51% female) treated with vedolizumab in Poland, of whom 55 were biologic-naïve and 45 biologic-exposed. The median duration of disease was 6 years. The disease duration was shorter in biologic-naïve than in biologic-exposed patients. Most patients were affected by extensive colitis (52%) or left-sided colitis (42%). Median disease activity was 10 according to the Total Mayo Score. Sixty-eight patients received concomitant systemic corticosteroids and 45 patients received immunomodulators. Our findings indicate that Polish patients receiving vedolizumab have a high disease activity and are treated relatively early after UC diagnosis. This might be due to the criteria for inclusion of a patient in the NDP.

Biological therapies have changed the landscape of pharmacological management of ulcerative colitis (UC). However, a large proportion of patients do not respond to biologics, lose their response over time, or present adverse drug events. This study aims to assess therapeutic response and treatment persistence to adalimumab, infliximab, and vedolizumab, 3 agents widely used in a tertiary referral center of Saguenay-Lac-Saint-Jean (Quebec, Canada).

We conducted a retrospective population-based study with a thorough review of patients' medical charts. Adults at UC diagnosis, with current or past use of adalimumab, infliximab, or vedolizumab, were included in the study. Clinical data were collected in order to assess response phenotypes and persistence to treatment. Kaplan-Meier curves were performed to assess treatment persistence, and predictors for discontinuation were assessed using Cox regression analyses.

A total of 134 patients were included in this study. For the cases exposed to adalimumab, infliximab, and vedolizumab, 56.9%, 62.5%, and 47.5% were responders, respectively. Mean persistence rates (95% CI) were 5.5 (4.3-6.6), 10.1 (8.7-11.5), and 3.6 (2.9-4.2) years for adalimumab, infliximab, and vedolizumab, respectively. Increased persistence rates were observed in biologic-naïve patients treated with infliximab in comparison to those with the previous exposition to 2 biologics, but no such effect was observed for adalimumab or vedolizumab. Overall, 61.9% of cases had adverse drug events and of these, 6 led to treatment discontinuation.

This study presents long-term treatment persistence data with adalimumab, infliximab, and vedolizumab, showing that more than half of cases treated with these biologics remained on treatment at least 24 months after initiation.

Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD).

This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn's disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL).

At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn's disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn's disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn's disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn's disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn's disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52.

Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.

Patients with Crohn's disease (CD) or ulcerative colitis (UC) often receive combination therapy with an immunomodulator and tumor necrosis factor antagonists, especially infliximab. However, the benefits of combination therapy with vedolizumab and ustekinumab are unclear.

We performed a retrospective study of patients with CD or UC initiating vedolizumab or ustekinumab therapy at Massachusetts General Hospital (USA), Alberta Health Sciences (Canada), or Nancy University Hospital (France) with at least 1 year of follow up. The primary outcome was clinical remission or response at week 14, based on the Harvey Bradshaw index for CD or simple clinical colitis index or partial Mayo score for UC. We separately examined week 30 and week 54 clinical outcomes, endoscopic response, and durability of therapy using multivariable regression models and adjusting for relevant confounders.

Our study included 549 patients (263 with UC, 286 with CD) receiving maintenance therapy with vedolizumab and 363 patients (4 with UC, 359 with CD) receiving maintenance therapy with ustekinumab with 1 year of follow up. The mean disease duration was 13-15 years. One-hundred thirty-one patients receiving vedolizumab (23.9%; 78 receiving thiopurine, 53 receiving methotrexate) and 120 patients receiving ustekinumab (33.1%, 57 receiving thiopurine, 63 receiving methotrexate) were receiving combination therapy. For vedolizumab, there was no difference in clinical response or remission with combination therapy vs monotherapy at week 14 (68.2% vs 74.1%; P = .22), week 30 (74.3% vs 75.6%; P = .78) or week 54 (78.3% vs 72.9%, P = .33). For ustekinumab, there was no difference in clinical response or remission with combination therapy vs monotherapy at week 14 (54.6% vs 65.8%; P = .08), week 30 (71.6% vs 77.4%; P = .33) or week 54 (62.1% vs 67.0%; P = .52). There were similar proportions of patients remaining on treatment or with endoscopic response at 1 year among patients receiving combination or monotherapy with vedolizumab or ustekinumab.

In patients with CD or UC initiating ustekinumab or vedolizumab therapy, combination therapy with immunomodulators did not increase rates of clinical remission or response, endoscopic remission, or persistence of therapy at 1 year.

Vedolizumab is increasingly used off-label to treat children and adolescents with inflammatory bowel disease (IBD). In the absence of rigorous clinical trial experience, multicenter observational data are important to establish expectations for efficacy and safety. We examined 1-year outcomes following vedolizumab therapy in a large multicenter pediatric IBD cohort.

We performed a retrospective study of 159 pediatric patients (4-17 years old) with IBD [78, Crohn disease (CD); 81, ulcerative colitis/IBD-unspecified (UC/IBD-U)] treated with vedolizumab for 1 year at 8 pediatric medical centers in the United States. Demographics, clinical outcomes, laboratory data, and vedolizumab dosing were recorded. The primary outcome was corticosteroid (CS)-free clinical remission at 1 year. Other measured outcomes were clinical remission at 12 and/or 24 weeks, laboratory outcomes at 1 year, and endoscopy/histology results at 1 year.

Among the 159 patients (mean age, 14.5 ± 2.4 years; 86% anti-TNF experienced), 68/159 (43%) achieved CS-free clinical remission at 1 year (CD, 35/78, 45%; UC/IBD-U, 33/81, 40%). Vedolizumab therapy failed and was discontinued in 33/159 (21%) patients prior to 1 year (CD, 18/78, 23%; UC/IBD-U, 15/81, 19%). While week 12 clinical remission was not predictive of 1-year clinical remission in either CD or UC/IBD-U, week 24 clinical remission was predictive of 1-year clinical remission only in CD patients. No infusion reactions or serious side effects were noted.

Vedolizumab was safe and effective in this pediatric population with approximately 43% achieving CS-free clinical remission at 1 year. Similar efficacy was noted in both CD and UC.

Although not as prominent, there are gender/sex differences in incidence/prevalence, clinical manifestation and disease course, comorbidities, therapeutic response, and patients coping strategy to the disease of inflammatory bowel disease (IBD). In this review, current knowledge about gender-specific differences in IBD would be provided and how to apply this in clinical practice be discussed.

Combining immunosuppressors has been proposed as a strategy to enhance treatment efficacy in Inflammatory Bowel Disease (IBD).

To summarize current evidence on combinations of targeted therapies with traditional immunosuppressors or with other targeted therapies.

A literature search on PubMed and Medline databases was performed to identify relevant articles.

Current evidence supports that the combination of infliximab and thiopurines is more effective than monotherapy with both agents in inducing remission in Crohn's Disease and Ulcerative colitis. Data on other combinations of other biologics and traditional immunosuppressors is lacking or show conflicting results. Vedolizumab seems a potentially effective maintenance regimen after calcineurin inhibitors-based rescue therapy in acute severe ulcerative colitis, as an alternative to thiopurines. Dual Targeted Therapy, which is the combination of 2 targeted therapies, might be a reasonable choice in patients with concomitant IBD and extraintestinal manifestations, or in patients with medical-refractory IBD who lack valid alternatives. Combinations with thiopurines are associated with an increased risk of infections and lymphoma. Data on other combinations is scarcer, but no specific safety issue has emerged so far.

Combination therapies seem to be effective in selected patients, with an overall acceptable safety profile.

There is debate over whether patients with inflammatory bowel diseases (IBD) treated with biologics that are not tumor necrosis factor antagonists (such as vedolizumab or ustekinumab) should receive concomitant treatment with immunomodulators. We conducted a meta-analysis to compare the efficacy and safety of concomitant immunomodulator therapy vs vedolizumab or ustekinumab monotherapy.

In a systematic search of publications, through July 31, 2019, we identified 33 studies (6 randomized controlled trials and 27 cohort studies) of patients with IBD treated with vedolizumab or ustekinumab. The primary outcome was clinical benefit, including clinical remission, clinical response, or physician global assessment in patients who did vs did not receive combination therapy with an immunomodulator. Secondary outcomes were endoscopic improvement and safety. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs.

Overall, combination therapy was not associated with better clinical outcomes in patients receiving vedolizumab (16 studies: OR, 0.84; 95% CI, 0.68-1.05; I2=13.9%; Q test P = .17) or ustekinumab (15 studies: OR, 1.1; 95% CI, 0.87-1.38; I2 = 11%; Q test P = .28). Results were consistent in subgroup analyses, with no difference in clinical remission or response in induction vs maintenance studies or in patients with Crohn's disease vs ulcerative colitis in studies of vedolizumab. Combination therapy was not associated with better endoscopic outcomes in patients receiving vedolizumab (3 studies: OR, 1.13; 95% CI, 0.48-2.68; I2 = 0; Q test P=.96) or ustekinumab (2 studies: OR, 0.58; 95% CI, 0.21-1.16; I2 = 47%; Q test P = .17). Combination therapy was not associated with an increase in adverse events during vedolizumab therapy (4 studies: OR, 1.17; 95% CI, 0.75-1.84; I2 = 0; Q test P = .110).

In a meta-analysis of data from studies of patients with IBD, we found that combining vedolizumab or ustekinumab with an immunomodulator is no more effective than monotherapy in induction or maintenance of remission.

This study aimed to compare real-world clinical effectiveness and safety of vedolizumab, an α4β7-integrin inhibitor, and anti-tumour necrosis factor-α [anti-TNFα] agents in biologic-naïve ulcerative colitis [UC] and Crohn's disease [CD] patients.

This was a 24-month retrospective medical chart study in adult UC and CD patients treated with vedolizumab or anti-TNFα in Canada, Greece and the USA. Inverse probability weighting was used to account for differences between groups. Primary outcomes were cumulative rates of clinical effectiveness [clinical response, clinical remission, mucosal healing] and incidence rates of serious adverse events [SAEs] and serious infections [SIs]. Secondary outcomes included cumulative rates of treatment persistence [patients who did not discontinue index treatment during follow-up] and dose escalation and incidence rates of disease exacerbations and disease-related surgeries. Adjusted analyses were performed using inverse probability weighting.

A total of 1095 patients [604 UC, 491 CD] were included. By 24 months, rates of clinical effectiveness were similar between groups, but incidence rates of SAEs (hazard ratio [HR] = 0.42 [0.28-0.62]) and SIs (HR = 0.40 [0.19-0.85]) were significantly lower in vedolizumab vs anti-TNFα patients. Rates of treatment persistence [p < 0.01] by 24 months were higher in vedolizumab patients with UC. Incidence rates of disease exacerbations were lower in vedolizumab patients with UC (HR = 0.58 [0.45-0.76]). Other outcomes did not significantly differ between groups.

In this real-world setting, first-line biologic therapy in biologic-naïve patients with UC and CD demonstrated that vedolizumab and anti-TNFα treatments were equally effective at controlling disease symptoms, but vedolizumab has a more favourable safety profile.