Systematic review with meta-analysis: real-world effectiveness and safety of vedolizumab in patients with inflammatory bowel disease.
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ABSTRACT: Background
Selective patient recruitment can produce discrepancies between clinical trial results and real-world effectiveness.Methods
A systematic literature review and meta-analysis were conducted to assess vedolizumab real-world effectiveness and safety in patients with ulcerative colitis (UC) or Crohn's disease (CD). MEDLINE, MEDLINE In-Process, EMBASE, and Cochrane databases were searched for real-world studies of vedolizumab in adult patients with UC/CD reporting clinical response, remission, corticosteroid-free remission, UC/CD-related surgery or hospitalization, mucosal healing, or safety published from May 1, 2014-June 22, 2017. Response and remission rates were combined in random-effects meta-analyses.Results
At treatment week 14, 32% of UC patients [95% confidence interval (CI) 27-39%] and 30% of CD patients (95% CI 25-34%) were in remission; and at month 12, 46% for UC (95% CI 37-56%) and 30% for CD (95% CI 20-42%). For UC, the rates of corticosteroid-free remission were 26% at week 14 (95% CI 20-34%) and 42% at month 12 (95% CI 31-53%); for CD they were 25% at week 14 (95%, CI 20-31%) and 31% at month 12 (95%, CI 20-45%). At month 12, 33-77% of UC and 6-63% of CD patients had mucosal healing. Nine percent of patients reported serious adverse events.Conclusions
Vedolizumab demonstrated real-world effectiveness in patients with moderate-to-severely active UC or CD, with approximately one-half and one-third of patients, respectively, in remission at treatment month 12. These findings are consistent with clinical trial data and support the long-term benefit-risk profile of vedolizumab.
SUBMITTER: Schreiber S
PROVIDER: S-EPMC6132930 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundVedolizumab is a gut-selective anti-lymphocyte trafficking agent approved for the treatment of moderate to severely active inflammatory bowel disease (IBD: ulcerative colitis [UC] and Crohn's disease [CD]).MethodsA systematic literature review (SLR) of real-world studies was conducted to assess the effectiveness of dose escalation of vedolizumab every 8 weeks (Q8W) during maintenance treatment to achieve a response in patients who were either vedolizumab responders experiencing secondary loss of response (SLOR) or non-responders. MEDLINE and EMBASE databases were searched from January 2014 to August 2021.ResultsScreening of SLR outputs identified 72 relevant real-world study publications featuring dose escalation of vedolizumab maintenance therapy. After qualitative review, ten eligible studies (9 articles, 1 abstract) were identified as reporting clinical response and/or clinical remission rates following escalation of intravenous vedolizumab 300 mg Q8W maintenance dosing to every 4 weeks (Q4W) maintenance dosing in adult patients with UC/CD (≥10 patients per study). Overall, 196/395 (49.6%) patients with IBD had a response within 54 weeks of vedolizumab maintenance dose escalation. Although definitions for clinical response/remission varied across the 10 studies, clinical response rates after escalated vedolizumab Q8W maintenance dosing ranged from 40.0% to 73.3% (9 studies) and from 30.0% to 55.8% for remission (4 studies) over a range of 8 to <58 weeks' follow-up.ConclusionsThis synthesis of real-world effectiveness data in vedolizumab-treated patients with IBD indicates that approximately half were able to achieve or recapture clinical response after escalating vedolizumab maintenance dosing.
| S-EPMC9802433 | biostudies-literature
Project description:BackgroundVedolizumab use in pediatrics is still off-label and the data are limited. We conducted a systematic review evaluating the efficacy and safety of vedolizumab in children and adolescents with inflammatory bowel disease (IBD).MethodsPubMed, EMBASE and Cochrane databases were systematically searched for studies of vedolizumab in children and adolescents with IBD reporting clinical remission, response, corticosteroid-free (CS-free) remission, mucosal healing, or safety up to December 3rd 2021.ResultsTen studies, comprising 455 patients were included. For CD, the pooled clinical remission rates were 25% (19/75) at 6 weeks, 28% (25/85) at 14 weeks, 32% (17/53) at 22 weeks, and 46% (43/92) at 1 year. For UC/IBD-U, the pooled clinical remission rates were 36% (25/70) at 6 weeks, 48% (52/101) at 14 weeks, 53% (24/45) at 22 weeks, and 45% (50/112) at 1 year. Mucosal healing was found in 17%-39% of CD and 15%-34% of UC/IBD-U respectively. Six percent of patients reported serious adverse events.ConclusionsAccording to low-quality evidence based on case series, approximately one-third and one-half of patients for CD and UC/IBD-U respectively achieved remission within 22 weeks, and about half of patients achieved remission at 1 year with reasonable safety profile. Long-term benefit profile data and high quality evidence are still needed.
| S-EPMC8978350 | biostudies-literature
Project description:BackgroundProspectively 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).MethodsThis 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).ResultsAt 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.ConclusionVedolizumab proved effective for the treatment of refractory IBD in clinical practice.
| S-EPMC8255566 | biostudies-literature
Project description:Background and aimsThere are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients.MethodsWe conducted a systematic review and meta-analysis to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe Crohn's disease or ulcerative colitis.ResultsWe identified six eligible Crohn's disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn's disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn's disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn's disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn's disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications.ConclusionsIndirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn's disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.
| S-EPMC9178865 | biostudies-literature
Project description:BackgroundSubcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions.AimTo 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.ResultsWe 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).ConclusionsSwitching 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.
| S-EPMC9540102 | biostudies-literature
Project description:BackgroundVedolizumab has since 2021 been available as a subcutaneous formulation. We aimed to assess 18-month drug persistence and possible predictive factors associated with discontinuation, safety, serum drug profile, drug dosing, and disease activity in a real-world cohort of patients with inflammatory bowel disease switched from intravenous to subcutaneous vedolizumab maintenance treatment.MethodsEligible patients were switched to subcutaneous vedolizumab and followed for 18 months or until discontinuation of subcutaneous treatment. Data on preferred route of administration, adverse events, drug dosing, serum-vedolizumab, disease activity, fecal calprotectin, and C-reactive protein were collected. Persistence was described using Kaplan-Meier analysis. The impact of clinical and biochemical variables on persistence was analyzed with Cox proportional hazard models.ResultsWe included 108 patients, and the estimated 18-month drug persistence was 73.6% (95% CI [64.2-80.1]). Patients in clinical remission at switch were less likely to discontinue SC treatment (HR = 0.34, 95% CI [0.16-0.73], P = .006), and patients favoring intravenous treatment at switch were almost 3 times more likely to discontinue (HR = 2.78, 95% CI [1.31-5.90], P = .008). Four patients discontinued subcutaneous vedolizumab due to injection site reactions. At 18 months, 88% of patients administered subcutaneous vedolizumab with an interval of ≥ 14 days, and serum-vedolizumab was 39.1 mg/L. Disease activity was stable during follow-up.ConclusionsThree of the four patients remained on subcutaneous vedolizumab after 18 months, a large proportion received treatment at standard dosing intervals, and disease activity remained stable. This indicates that switching from intravenous to subcutaneous vedolizumab treatment is convenient and safe.
| S-EPMC10972549 | biostudies-literature
Project description:BackgroundDeep remission (DR) is a treatment target in IBD associated with reduced hospitalization and improved outcome. Randomized control trial (RCT) data demonstrates efficacy of anti-TNFα agents in achieving DR; however, real-world data (RWD) can provide information complementary to RCTs, specifically regarding treatment duration. In this systematic review with meta-analysis, we use real-world data (RWD) to determine rates of DR in IBD treated with anti-TNFα.MethodsWe completed a systematic search of MEDLINE and EMBASE on July 8, 2019 with review of major gastrointestinal conference abstracts from 2012 to 2019. Studies utilizing RWD (data not from phase I-III RCTs) of adult IBD patients treated with anti-TNFα agents were included. DR was defined by clinical and endoscopic remission at minimum. DR was assessed at 8 weeks, 6 months, 1 year, and 2 years. Risk of bias was assessed with the Newcastle Ottawa Scale.Results29,033 publications were identified. Fifteen publications, nine manuscripts and six conference abstracts, were included encompassing 1212 patients (769 Crohn's disease-CD, 443 ulcerative colitis-UC), and analyzed using Comprehensive Meta-Analysis. Rate of DR was 36.4% (95% CI 12.6-69.4%) at 8 weeks, 39.1% (95% CI 10.4-78%) at 6 months, 44.4% (95% CI 34.6-54.6%) at 1 year, and 36% (95% CI 18.7-58%) at 2 years. DR in CD at 1 year was 48.6% (95% CI 32.8-64.7%) and in UC was 43.6% (95% CI 32.8-55.1%).ConclusionsThe rate of DR was highest after 1 year of therapy, in nearly 45% of IBD patients treated with anti-TNFα. Similar rates were achieved between patients with UC and CD. The findings highlight the efficacy of anti-TNFα in real-world setting. Future studies using RWD can determine efficacy of newer IBD therapeutics in routine clinical practice.
| S-EPMC8335971 | biostudies-literature
Project description:BackgroundVedolizumab, a gut-selective α4 β7 integrin antibody, is approved for moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD).AimTo report the final results from the vedolizumab GEMINI long-term safety (LTS) study.MethodsThe phase 3, open-label GEMINI LTS study (initiated May 2009) enrolled patients with UC or CD from four prior clinical trials and vedolizumab-naïve patients. Vedolizumab LTS was evaluated; efficacy and patient-reported outcomes were exploratory endpoints.ResultsEnrolled patients (UC, n = 894; CD, n = 1349) received vedolizumab 300 mg IV every 4 weeks; median cumulative exposure was 42.4 months (range: 0.03-112.2) for UC and 31.5 months (range: 0.03-100.3) for CD. Over 8 years, adverse events (AEs) occurred in 93% (UC) and 96% (CD) of patients, with UC (36%) and CD (35%) exacerbations most frequent. Serious AEs were reported for 31% (UC) and 41% (CD) of patients. Vedolizumab discontinuation due to AEs occurred in 15% (UC) and 17% (CD) of patients. There were no new trends for infections, malignancies, infusion-related reactions, or hepatic events, and no cases of progressive multifocal leukoencephalopathy. Of the ten deaths (UC, n = 4; CD, n = 6), two were considered drug-related by local investigators (West Nile virus infection-related encephalitis and hepatocellular carcinoma). Continuous vedolizumab maintained clinical response long-term, with 33% (UC) and 28% (CD) of patients in clinical remission at 400 treatment weeks.ConclusionsThe safety profile of vedolizumab remains favourable with no unexpected or new safety concerns. These results further establish the safety of vedolizumab and support its long-term use (NCT00790933/EudraCT 2008-002784-14).
| S-EPMC7540482 | biostudies-literature
Project description:BackgroundTo date, coronavirus disease 2019 (COVID-19) becomes increasingly fierce due to the emergence of variants. Rapid herd immunity through vaccination is needed to block the mutation and prevent the emergence of variants that can completely escape the immune surveillance. We aimed to systematically evaluate the effectiveness and safety of COVID-19 vaccines in the real world and to establish a reliable evidence-based basis for the actual protective effect of the COVID-19 vaccines, especially in the ensuing waves of infections dominated by variants.MethodsWe searched PubMed, Embase and Web of Science from inception to July 22, 2021. Observational studies that examined the effectiveness and safety of SARS-CoV-2 vaccines among people vaccinated were included. Random-effects or fixed-effects models were used to estimate the pooled vaccine effectiveness (VE) and incidence rate of adverse events after vaccination, and their 95% confidence intervals (CI).ResultsA total of 58 studies (32 studies for vaccine effectiveness and 26 studies for vaccine safety) were included. A single dose of vaccines was 41% (95% CI: 28-54%) effective at preventing SARS-CoV-2 infections, 52% (31-73%) for symptomatic COVID-19, 66% (50-81%) for hospitalization, 45% (42-49%) for Intensive Care Unit (ICU) admissions, and 53% (15-91%) for COVID-19-related death; and two doses were 85% (81-89%) effective at preventing SARS-CoV-2 infections, 97% (97-98%) for symptomatic COVID-19, 93% (89-96%) for hospitalization, 96% (93-98%) for ICU admissions, and 95% (92-98%) effective for COVID-19-related death, respectively. The pooled VE was 85% (80-91%) for the prevention of Alpha variant of SARS-CoV-2 infections, 75% (71-79%) for the Beta variant, 54% (35-74%) for the Gamma variant, and 74% (62-85%) for the Delta variant. The overall pooled incidence rate was 1.5% (1.4-1.6%) for adverse events, 0.4 (0.2-0.5) per 10 000 for severe adverse events, and 0.1 (0.1-0.2) per 10 000 for death after vaccination.ConclusionsSARS-CoV-2 vaccines have reassuring safety and could effectively reduce the death, severe cases, symptomatic cases, and infections resulting from SARS-CoV-2 across the world. In the context of global pandemic and the continuous emergence of SARS-CoV-2 variants, accelerating vaccination and improving vaccination coverage is still the most important and urgent matter, and it is also the final means to end the pandemic.
| S-EPMC8590867 | biostudies-literature
Project description:BACKGROUND:The promise of real-world evidence (RWE) is especially relevant to pediatrics, where medicines prescribed for children are often used without evidence derived from randomized clinical trials. OBJECTIVES:The aim of this systematic review was to describe the state of RWE in pediatrics by identifying observational studies published during 2016 that used RWE to assess medication safety or effectiveness in children. METHODS:An electronic search of PubMed was combined with an extended search of references within systematic reviews and expert suggestions. Studies were included if they reported on an infant or child under 18 years with exposure to medications; assessed safety or effectiveness; specified a comparison or control group, and were published in English in 2016. Data extraction was conducted by one team member using a standardized form and reviewed by a second team member. Study quality was assessed using the GRACE checklist for rating the quality of observational studies. RESULTS:After removing duplicates, 915 citations were screened and 29 studies met the eligibility criteria. Most of the eligible studies relied on primary data collection or chart review at a single institution and did not use the growing number of administrative or electronic health record databases available. One-quarter of the studies did not use well-established statistical methods to control for confounders. No single disease group or medication predominated, and age groups ranged from infants to adolescents. CONCLUSIONS:A small body of observational studies published in 2016 were categorized by the study team as using real-world data to assess medication safety or effectiveness in children. Studies varied in age groups, diseases or conditions, and methods, and may not have fully met the FDA definition of RWE. Our review indicates that the use of RWE is not fully developed in pediatrics, and suggests an opportunity to further develop capabilities and more fully leverage administrative and electronic health record databases to study medication safety and effectiveness in children. Our systematic review appears generalizable to pediatrics broadly, and documents that the high level of activity in RWE in general has had less of an impact on pediatrics.
| S-EPMC7221095 | biostudies-literature