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, 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).
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Project description:BACKGROUND:There has been limited evaluation of the association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases (IBD). AIM:To perform a systematic review and meta-analysis to evaluate the potential role of therapeutic drug monitoring (TDM) for vedolizumab. METHODS:Through a systematic literature search through 28 February 2019, we identified five cohort studies (558 patients, 42% with ulcerative colitis) reporting the association between vedolizumab trough concentration and clinical outcomes in patients with IBD. We calculated mean difference (MD) in vedolizumab trough concentration in patients achieving vs not achieving clinical outcomes, and qualitatively synthesized thresholds associated with favourable outcomes. RESULTS:In patients with UC, median vedolizumab trough concentrations were consistently higher in patients achieving clinical remission (median, 14.3 ?g/mL vs 10.5 ?g/mL; MD, 5.1 ?g/mL, 95% CI, 2.8-7.4) or endoscopic remission (median, 13.0 ?g/mL vs 9.7; MD, 5.1 ?g/mL, 95% CI, 2.2-7.9). In patients with CD, there was no significant difference in median vedolizumab trough concentrations in patients achieving vs not achieving clinical remission (MD, 2.0 ?g/mL; 95% CI, -0.5 to 4.5) or endoscopic remission (MD, 3.6 ?g/mL; 95% CI, -1.4 to 8.6). In patients with UC, week 6 vedolizumab trough concentrations ?18.5-20.8 ?g/mL, and maintenance trough concentrations ?9.0-12.6 ?g/mL were associated with favourable clinical outcomes. Antibodies to vedolizumab were reported in 1.7%-3.0% patients on maintenance therapy. CONCLUSION:Based on meta-analysis, patients with UC who achieve endoscopic and clinical remission have significantly higher vedolizumab trough concentration during maintenance therapy. Vedolizumab trough concentration >20 ?g/mL at week 6, and >12 ?g/mL during maintenance may be associated with better outcomes, though cause-effect relationship remains unclear. Prospective studies on reactive and proactive therapeutic drug monitoring of vedolizumab (vs empiric dose escalation) are warranted.
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Project description:Background: Vedolizumab (vedo) is effective for induction and maintenance of remission in adults with inflammatory bowel disease (IBD). Pediatric data are still limited, especially for the youngest children with very early onset disease (VEO-IBD). The aim of this study was to assess the safety and efficacy of vedo in VEO-IBD. Methods: We performed a retrospective review of pediatric IBD patients with VEO-IBD (defined as aged <6 years) receiving vedo. Data on demographics, disease behavior, activity, and previous treatments/surgeries were collected. Disease activity was assessed using the pediatric Crohn's disease (CD) activity index (PCDAI) for CD or pediatric ulcerative colitis (UC) activity index (PUCAI) for UC. Primary outcome was clinical response after induction therapy with vedolizumab (4th dose week). It was defined as a decrease in PCDAI of at least 12.5 points between baseline and 4th dose week for CD, and a decrease in PUCAI of at least 20 points between baseline and this time for UC. Descriptive statistics were performed to analyze the data. Results: The study included 16 patients with VEO-IBD who have received vedo: 4/16 (25%) with CD, and 12/16 (75%) with UC at the median age of diagnosis 33.7 months (6.6 months-4.5 years). Median age at vedo initiation was 6.5 years (2.2-16.5 years). Among the analyzed individuals, 56.25% had failed more than one anti-tumor necrosis factor (TNF) alfa agent. Clinical response at 4th dose week was observed in 9/16 (56.3%) patients: mean baseline PCDAI score was 34.4 ± 1.9 and 10.6 ± 1.8 after induction therapy with vedo, while PUCAI score was 26 ± 6 vs. 18 ± 8, respectively. There was improvement in patients' nutritional state: at baseline 2/16 (12.5%) children had body mass index (BMI) below 1 percentile and no child had such BMI after induction therapy with vedo. No infusion reactions or serious adverse events/infections were reported. Conclusion: Vedolizumab is safe and effective in the medical management of pediatric patients with VEO-IBD.
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Project description:Background & aimsThere are few real-world data on the safety of vedolizumab for treatment of Crohn's disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice.MethodsWe performed a retrospective review of data from a multicenter consortium database (from May 2014 through June 2017). Infectious and non-infectious adverse events were defined as those requiring antibiotics, hospitalization, vedolizumab discontinuation, or resulting in death. Rates were quantified as proportions and events per 100 patient years of exposure (PYE) or follow up (PYF). We performed multivariable logistic regression analyses to identify factors significantly associated with events and reported as odds ratios (OR) with 95% CIs.ResultsOur analysis comprised 1087 patients (650 with CD and 437 with UC; 55% female; median age, 37 years) with 861 PYE and 955 PYF. Infections were observed in 68 patients (6.3%; 7.9 per 100 PYE, 7.1 per 100 PYF); gastrointestinal infections (n = 31, 2.4 per 100 PYE, 2.2 per 100 PYF) and respiratory infections (n = 14, 1.6 per 100 PYE, 1.5 per 100 PYF) were the most common. Arthralgias were the most common non-infectious adverse events (n = 31, 2.9%; 3.6 per 100 PYE). Two patients developed malignancies (squamous cell skin cancer and colorectal cancer; 0.23 per 100 PYE, 0.21 per 100 PYF). Active smoker status (OR, 3.39) and number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used were independently associated with infections.ConclusionIn a retrospective cohort study of patients with IBD, we found vedolizumab to be well tolerated with an overall favorable safety profile. Active smoking and concomitant use of immunosuppressive agents were independently associated with infections.
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