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Vedolizumab Immunogenicity With Long-Term or Interrupted Treatment of Patients With Inflammatory Bowel Disease.

ABSTRACT: 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.

SUBMITTER: Wyant T

PROVIDER: S-EPMC8456828 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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].

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.

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Vedolizumab Immunogenicity With Long-Term or Interrupted Treatment of Patients With Inflammatory Bowel Disease.

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