Dataset Information

Long-term safety of vedolizumab for inflammatory bowel disease.

ABSTRACT:

Background

Vedolizumab, a gut-selective α₄ β₇ integrin antibody, is approved for moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD).

Aim

To report the final results from the vedolizumab GEMINI long-term safety (LTS) study.

Methods

The 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.

Results

Enrolled 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.

Conclusions

The 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).

SUBMITTER: Loftus EV

PROVIDER: S-EPMC7540482 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Long-term safety of vedolizumab for inflammatory bowel disease.

Loftus Edward V EV Feagan Brian G BG Panaccione Remo R Colombel Jean-Frédéric JF Sandborn William J WJ Sands Bruce E BE Danese Silvio S D'Haens Geert G Rubin David T DT Shafran Ira I Parfionovas Andrejus A Rogers Raquel R Lirio Richard A RA Vermeire Séverine S

Alimentary pharmacology & therapeutics 20200902 8

<h4>Background</h4>Vedolizumab, a gut-selective α<sub>4</sub> β<sub>7</sub> integrin antibody, is approved for moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD).<h4>Aim</h4>To report the final results from the vedolizumab GEMINI long-term safety (LTS) study.<h4>Methods</h4>The 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 ...[more]

PMID: 32876349

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Project description:Patients in the GEMINI 1 or 2 study (NCT00790933; Eudra CT2008-002784-14) with ulcerative colitis or Crohn disease had low immunogenicity rates after vedolizumab treatment for up to 52 weeks. We report immunogenicity rates from the GEMINI long-term safety (LTS) study using a new drug-tolerant electrochemiluminescence assay, including analyses in patients who received continuous vedolizumab induction and maintenance in GEMINI 1 or 2 and long term safety, or vedolizumab induction and placebo maintenance in GEMINI 1 or 2 followed by re-treatment in long term safety (treatment interruption). Patients were enrolled in GEMINI long term safety from GEMINI 1, 2, or 3, or as de novo vedolizumab-treated patients; all received vedolizumab 300 mg intravenously every 4 weeks. Vedolizumab antidrug antibody (ADA) status was determined by electrochemiluminescence assay; ADA-positive samples were characterized by neutralizing activity. Vedolizumab ADA data were available for 1753 patients: 1513 continuously treated with vedolizumab before/during GEMINI long term safety, 240 re-treated after treatment interruption. Among continuously treated patients, 36 (2.4%) were ADA positive (15 persistently, 20 neutralizing ADA positive). Among re-treated patients, 53 (22.1%) were ADA positive (42 persistently, 40 neutralizing ADA positive). Longitudinal immunogenicity rates increased during placebo maintenance (19.4% at week 52), then decreased in GEMINI long term safety to rates (0 at the final visit) similar to continuously treated patients. ADA positivity was 1.1% vs 2.5% (continuous treatment) and 23.1% vs 22.0% (re-treatment) among patients with and without infusion-related reactions, respectively. Long-term vedolizumab treatment was associated with generally low immunogenicity rates; vedolizumab-re-treated patients had higher rates during placebo maintenance, which decreased during re-treatment. No relationship was observed between immunogenicity and infusion-related reactions.

Project description:BackgroundReal-world data on long-term outcomes of vedolizumab (VDZ) are scarce.ObjectiveTo assess long-term outcomes (up to 3 years) of VDZ in treating inflammatory bowel disease (IBD).DesignA nationwide, prospective multicentre extension of a Swedish observational study on VDZ assessing Effectiveness And Healthcare resource utilization in patients with IBD (SVEAH).MethodsAfter re-consent, data of patients with Crohn's disease (CD) (n = 68) and ulcerative colitis (UC) (n = 46) treated with VDZ were prospectively recorded using an electronic case report form integrated with the Swedish IBD Register (SWIBREG). The primary outcome was clinical remission (defined as Harvey-Bradshaw Index ⩽4 in CD and partial Mayo score ⩽2 in UC) at 104 and 156 weeks in patients with a response and/or remission 12 weeks after starting VDZ. Secondary outcomes included health-related quality of life (HRQoL) and biochemical outcomes.ResultsVDZ continuation rates were high at weeks 104 and 156, 88% and 84%, respectively, for CD and 87% and 78%, respectively, for UC. Of the 53 CD patients with a response/remission at 12 weeks, 40 (75%) patients were in remission at 104 weeks and 42 (79%) patients at 156 weeks. For UC, these numbers were 25/31 (81%) and 22/31 (71%), respectively. Improvements were seen in the Short Health Scale (p < 0.01 for each dimension; CD, n = 51; UC, n = 33) and the EuroQol 5-Dimensions, 5-levels index value (p < 0.01; CD, n = 39; UC, n = 30). Median plasma-C-reactive protein concentrations (mg/L) decreased from 5 at baseline to 4 in CD (p = 0.01, n = 53) and from 5 to 4 in UC (p = 0.03, n = 34) at 156 weeks. Correspondingly, median faecal-calprotectin (µg/g) decreased from 641 to 114 in CD patients (p < 0.01, n = 26) and from 387 to 37 in UC patients (p = 0.02, n = 17).ConclusionVDZ demonstrated high continuation rates and was associated with improvements in clinical outcomes, HRQoL measures and inflammatory markers at 2 and 3 years after treatment initiation in this prospective national SVEAH extension study.RegistrationENCePP registration number: EUPAS22735.

Project description:BackgroundVedolizumab (VDZ) is a well-established and important therapeutic option in the treatment of patients with inflammatory bowel disease (IBD). However, the significance of therapeutic drug monitoring (TDM) with VDZ remains a contradictory field in daily clinical practice. Our study aims to clarify the predictive impact of VDZ drug levels in long-term clinical outcomes in a real-world cohort.MethodsPatients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD) from a tertiary IBD referral center at the University Hospital Augsburg, Germany, were enrolled in this single-center retrospective data analysis. Clinical and endoscopic data were collected at month 6, month 12, and at the last time of follow-up, and outcomes were correlated with VDZ levels at week 6.ResultsThis study included 95 patients, 68.4% (n = 65) with UC, 24.2% (n = 23) with CD, and 7.4% (n = 7) with indeterminate colitis (CI). Patients with a mean VDZ treatment time of 17.83 months ± 14.56 showed clinical response in 29.5% (n = 28) and clinical remission in 45.3% (n = 43) at the end of the study. Endoscopic response occurred in 20.0% (n = 19) and endoscopic remission in 29.5% (n = 28) at the end of the study. The sustained beneficial effect of VDZ was also reflected in a significant change in biomarker levels. VDZ trough level at week 6 was determined in 48.4% (n = 46) with a mean of 41.79 µg/mL ± 24.58. A significant association between VDZ level at week 6 and both short and long-term outcomes could not be demonstrated. However, numerically higher VDZ levels were seen in patients with endoscopic and clinical improvement at month 6 and at the time of last follow-up.ConclusionsThis study demonstrated efficacy and safety for VDZ in a real-world cohort. Although, for some parameters, a clear trend for higher VDZ levels at week 6 was seen, the efficacy of VDZ was not significantly correlated to VDZ level at week 6, which questions the predictive value of VDZ levels in the real world.

Project description:Background and aimsExtraintestinal manifestations [EIMs] such as arthritis/arthralgia are common in inflammatory bowel disease. We performed post hoc analyses of data from the GEMINI studies to evaluate the effect of vedolizumab, a gut-selective anti-trafficking agent, on arthritis/arthralgia.MethodsSustained resolution of baseline arthritis/arthralgia, worsening of baseline arthritis/arthralgia, the occurrence of new arthritis/arthralgia, and the composite of new/worsening arthritis/arthralgia were evaluated. Cox modelling was used for time-to-event analysis. The influence of corticosteroid-tapering was also investigated.ResultsIn Crohn's disease [CD] patients, vedolizumab was significantly less likely than placebo to be associated with new/worsening arthritis/arthralgia (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44-0.89). Similar incidences of sustained resolution of arthritis/arthralgia occurred with vedolizumab and placebo. In CD patients on corticosteroids at baseline, a decrease in corticosteroid dose increased the risk of new/worsening arthritis/arthralgia (odds ratio [OR], 7.49; 95% CI, 3.50-15.97) regardless of treatment; and in those achieving corticosteroid-free status, arthritis/arthralgia was less likely with vedolizumab than with placebo [HR, 0.14; 95% CI, 0.05-0.35]. In ulcerative colitis [UC] patients, vedolizumab and placebo showed a similar incidence of new/worsening of arthritis/arthralgia. In UC patients on corticosteroid at baseline, arthritis/arthralgia was more likely in those achieving corticosteroid-free status than in those continuing corticosteroids (HR 2.63 [95% CI 1.13-6.11]); and in those achieving corticosteroid-free status, the incidence of arthritis/arthralgia was similar with vedolizumab and placebo.ConclusionsVedolizumab therapy was associated with a reduced likelihood of new/worsening arthritis/arthralgia in CD and no increased incidence of these events in UC.Studies included [clincialtrials.gov, number]GEMINI 1 [NCT00783718]; GEMINI 2 [NCT00783692]; GEMINI 3 [NCT01224171].

Dataset Information

Long-term safety of vedolizumab for inflammatory bowel disease.

Background

Aim

Methods

Results

Conclusions

Publications

Long-term safety of vedolizumab for inflammatory bowel disease.

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