Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis.
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ABSTRACT: Background & aims
We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice.Methods
A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately.Results
A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754).Conclusions
Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.
SUBMITTER: Lukin D
PROVIDER: S-EPMC8026779 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDirect comparisons are lacking between vedolizumab and tumour necrosis factor (TNF)-antagonist therapy in Crohn's disease (CD).AimTo compare safety and effectiveness of vedolizumab and TNF-antagonist therapy in adult CD patients.MethodsRetrospective observational cohort (May 2014-December 2017) propensity score-weighted comparison of vedolizumab vs TNF-antagonist therapy (infliximab, adalimumab, certolizumab) in CD. Propensity scores were weighted for age, prior treatments, disease complications, extent and severity, steroid dependence, and concomitant immunosuppressive drug use. The primary outcome was comparative risk for infections or non-infectious serious adverse events (requiring antibiotics, antivirals, antifungals, hospitalisation, or treatment discontinuation, or resulting in death). Secondary comparative effectiveness outcomes were clinical remission (resolution of CD-related symptoms), steroid-free clinical remission and endoscopic remission (absence of ulcers/erosions).ResultsWe included 1266 patients (n = 659 vedolizumab). Rates of non-infectious serious adverse events (odds ratio [OR] 0.072, 95% confidence interval [CI] 0.012-0.242), but not serious infections (OR 1.183, 95% CI 0.786-1.795), were significantly lower with vedolizumab vs TNF-antagonist therapy. Safety comparisons for non-infectious serious adverse events remained significant after adjusting for differences in duration of exposure. No significant difference was observed between vedolizumab and TNF-antagonist therapy for clinical remission (hazard ratio [HR] 0.932, 95% CI 0.707-1.228), steroid-free clinical remission (HR 1.250, 95% CI 0.677-2.310) or endoscopic remission (HR 0.827, 95% CI 0.595-1.151). TNF-antagonist therapy was associated with higher treatment persistence compared with vedolizumab.ConclusionsThere was a lower risk of non-infectious serious adverse events, but not serious infections, with vedolizumab vs TNF-antagonist therapy, with no significant difference for achieving disease remission.
| S-EPMC7496810 | biostudies-literature
Project description:BackgroundReal-world comparisons of biologic treatment outcomes for ulcerative colitis (UC) or Crohn's disease (CD) patients are limited. We sought to evaluate the real-world effectiveness of vedolizumab (VDZ) and anti-tumor necrosis factor alpha (anti-TNFα) in UC and CD patients in Germany.MethodsA retrospective chart review (15 sites) investigated UC and CD patients who were biologic-treatment naïve (biologic-naïve) or had received no more than one prior anti-TNFα before initiating treatment with VDZ or anti-TNFα between 15 July 2014 and 20 October 2015. Kaplan-Meier analyses assessed time to first chart-documented clinical remission (CR) and symptom resolution (UC: rectal bleeding [RB], stool frequency [SF]; CD: abdominal pain [AP], liquid stools [LS]) and outcome duration.ResultsA total of 133 UC (76 VDZ; 57 anti-TNFα) and 174 CD (69 VDZ; 105 anti-TNFα) patients were included. By Week 26, estimated cumulative rates of patients achieving CR or symptom resolution with VDZ vs anti-TNFα treatment were for UC: CR, 53.7% vs 31.7%; RB, 66.8% vs 55.8%; and SF, 59.8% vs 50.7%, respectively; and for CD: CR, 14.4% vs 32.8%; AP, 62.5% vs 56.0%; and LS, 29.9% vs 50.3%, respectively. Outcomes were sustained similarly between treatments, except RB (VDZ vs anti-TNFα: median 38.1 vs 15.1 weeks, P = 0.03). Treatment-related adverse events occurred in 5.3% vs 7.0% (UC) and 8.7% vs 19.0% (CD) of VDZ vs anti-TNFα patients, respectively.ConclusionsAlthough there were differences in CR, symptom resolution, and safety profiles, real-world data support both VDZ and anti-TNFα as effective treatment options in UC and CD.
| S-EPMC7341567 | biostudies-literature
Project description:Ulcerative colitis (UC) and Crohn's disease (CD) are chronic, relapsing inflammatory bowel diseases associated with significant morbidity. Conventional therapies for these diseases include corticosteroids, aminosalicylates, immunomodulators, and monoclonal antibodies. Over the years tumor necrosis factor (TNF)-α antagonists alone or in combination with other therapies have emerged as the cornerstone of treatment for induction and maintenance of remission of moderate to severe UC and CD. Unfortunately, some patients with moderate to severe UC and CD are unable to attain or maintain remission with TNF-α antagonist treatment. Vedolizumab, a humanized monoclonal antibody, is the first integrin receptor antagonist approved that selectively antagonizes α4β7 gastrointestinal integrin receptors. US Food and Drug Administration approval is for treatment of patients with moderate to severe active UC and CD who have inadequate response with, lost response to, or are intolerant to a TNF-α antagonist or an immunomodulator; or have inadequate response with, are intolerant to, or demonstrate dependence on corticosteroids. When administered according to approved dosing in patients with moderate to severe CD and UC, vedolizumab induces clinical response rates up to 31.4% and 47.1% at week 6, and clinical remission rates up to 39% and 41.8% at week 52, respectively. Serious adverse events reported with vedolizumab include serious infections, malignancies, and anaphylaxis. Since vedolizumab is gastrointestinal selective, to date, it has not shown evidence of causing progressive multifocal leukoencephalopathy; however, postmarketing studies monitoring for this adverse effect are ongoing. Further assessment of vedolizumab earlier in the course of these diseases and in combination with other therapies is warranted.
| S-EPMC4549690 | biostudies-literature
Project description:ObjectiveThe aim was to evaluate the cost-effectiveness of Crohn's disease (CD) treatment with vedolizumab and ustekinumab after failure of therapy with tumor necrosis factor-α antagonists (anti-TNFs).MethodsThe Markov model incorporated the lifetime horizon, synthesis-based estimates of biologics' efficacy in relation to anti-TNF exposure, and administration of biologics reflecting clinical practice (e.g., sequence of biologics, retreatment, 12-month treatment). The utilities, non-medical costs and indirect costs were derived from a study of 200 adult patients with CD, while the healthcare costs were from a study of 1393 adults with CD who used biologics in Poland. The quality-adjusted life years (QALYs) and costs (the societal perspective) were discounted with the annual rates of 3.5 and 5%, respectively.ResultsThe addition of vedolizumab (ustekinumab) to the sequence of available anti-TNFs (after first-line infliximab or after second-line adalimumab) led to a gain of 0.364 (0.349) QALYs at an additional cost of €5600.24 (€6593.82). The incremental cost-effectiveness ratios (ICERs) were €15,369 [95% confidence interval (CI) 7496-61,354] and €18,878 (95% CI 9213-85,045) per QALY gained with vedolizumab and ustekinumab, respectively. Sensitivity analyses revealed a high impact on the ICERs of the relapse rate after discontinuation of biologic treatment. The highest value of vedolizumab/ustekinumab was estimated after the failure of therapies with both anti-TNFs.ConclusionsCD treatment with ustekinumab or vedolizumab after failure of anti-TNF therapy appears to be cost-effective at a threshold of €31,500. The replacement of the second-line anti-TNF with ustekinumab/vedolizumab and the course of the disease after discontinuation of biologics are influential drivers of the cost-effectiveness.
| S-EPMC5999163 | biostudies-literature
Project description:Ulcerative Colitis (UC) is an inflammatory bowel disease typically affecting the colon. Patients with active UC have elevated tumor necrosis factor (TNF) concentrations in serum and colonic tissue. Infliximab is a monoclonal antibody directed against TNF and binds with high affinity. Target-mediated drug disposition (TMDD) is reported for monoclonal antibodies meaning that their pharmacokinetics are affected by high target affinity. Here, a TMDD model is proposed to describe the interaction between infliximab and TNF in UC patients. Data from 20 patients with moderate to severe UC was used. Patients received standard infliximab induction therapy (5 mg kg-1) at week 0, followed by infusions at week 2 and 6. IFX, anti-drug antibodies and TNF serum concentrations were measured at day 0 (1 h after infusion), 1, 4, 7, 11, 14, 18, 21, 28 and 42. A binding model, TMDD model, and a quasi-steady state (QSS) approximation were evaluated using nonlinear mixed effects modeling (NONMEM). A two-compartment model best described the concentration-time profiles of infliximab. Typical clearance of infliximab was 0.404 L day-1 and increased with the presence of anti-drug antibodies and with lower albumin concentrations. The TMDD-QSS model best described the pharmacokinetic and pharmacodynamics data. Estimate for TNF baseline (Bmax was 19.8 pg mL-1 and the dissociation constant (Kss) was 13.6 nM. This model could eventually be used to investigate the relationship between suppression of TNF and the response to IFX therapy.
| S-EPMC6868113 | biostudies-literature
Project description:ImportanceObservational comparative effectiveness studies can inform the positioning of biologic therapies for older patients with inflammatory bowel disease (IBD) who are underrepresented in clinical trials.ObjectiveTo compare the effectiveness and safety of vedolizumab vs tumor necrosis factor (TNF) for older patients with IBD.Design, setting, and participantsThis active comparator, new-user design, comparative effectiveness study was conducted between January 1, 2005, and December 31, 2018, among 754 older patients (aged ≥50 years) with IBD from the Danish National Patient Register. The mean follow-up after treatment initiation took place at 32 to 40 weeks. Statistical analysis was performed from February 1 to April 27, 2022.InterventionsTreatment with vedolizumab or TNF antagonists.Main outcomes and measuresThe primary effectiveness outcome was treatment failure, defined as the composite risk of IBD-related hospitalization, IBD-related surgery, or a new corticosteroid prescription more than 6 weeks after initiation of treatment with biologic therapy. Secondary effectiveness outcomes were time to each individual component of the composite effectiveness outcome. The primary safety outcome was the risk of serious infections, defined as infections requiring hospitalization. A 1:1 propensity score-matched analysis was conducted, accounting for patient-, disease-, and treatment-associated factors.ResultsThe study compared 377 older patients with IBD with incident use of vedolizumab (202 women [53.6%]; mean [SD] age, 61.2 [8.3] years; 177 [46.9%] with Crohn disease) vs 377 patients with incident use of TNF antagonists (206 women [54.6%]; mean [SD] age, 61.3 [8.1] years; 182 [48.3%] with Crohn disease). Overall, vedolizumab was associated with an increased risk of treatment failure compared with TNF antagonists (1-year risk, 45.4% vs 34.7%; adjusted hazard ratio [HR], 1.31; 95% CI, 1.02-1.69), including higher risk of IBD-related hospitalization (1-year risk, 27.8% vs 16.3%; adjusted HR, 1.48; 95% CI, 1.03-2.15) and IBD-related major abdominal surgery (1-year risk, 21.3% vs 8.0%; adjusted HR, 2.39; 95% CI, 1.45-3.94). In subgroup analysis by IBD phenotype, among patients with Crohn disease, vedolizumab was associated with a 77% higher risk of treatment failure (adjusted HR, 1.77; 95% CI, 1.21-2.58), while no difference in risk of treatment failure was seen among patients with ulcerative colitis (adjusted HR, 1.04; 95% CI, 0.75-1.43; P = .03 for interaction). There was no significant difference in the risk of serious infections, overall (1-year risk, 8.2% vs 8.7%; adjusted HR, 1.04; 95% CI, 0.58-1.85) and by IBD phenotype.Conclusions and relevanceIn this comparative effectiveness study of older patients with IBD, vedolizumab was associated with a higher risk of treatment failure compared with TNF antagonists, particularly among patients with Crohn disease, without offering a significant safety advantage.
| S-EPMC9526086 | biostudies-literature
Project description:BackgroundReal-world comparative benefits and risks of infliximab (IFX) and adalimumab (ADA) in patients with ulcerative colitis (UC) are unclear.AimTo evaluate the comparative effectiveness and safety of IFX and ADA in patients with UC who were new users of anti-TNF agents.MethodsUsing an administrative claims database (Optum Labs Data Warehouse), we identified patients who received first anti-TNF (IFX, ADA) prescription after a 12-month period without any anti-TNF treatment (baseline), and with a minimum 6-month follow-up after anti-TNF initiation. Primary outcome measures were: all-cause and UC-related hospitalisation, abdominal surgery, corticosteroid use >60 days after starting anti-TNF, and serious infections. We performed 2:1 propensity-score matched Cox proportional hazard analysis, and inverse probability-of-treatment weight (IPTW) analysis, accounting for healthcare utilisation, comorbidities and use of UC-related medication.ResultsWe included 1400 new users of anti-TNF agents (age, 43 ± 15 years; 52% males), from 2006 to 2014. On propensity-score matched analysis, there was no significant difference in the risk of UC-related hospitalisation [IFX vs. ADA; adjusted hazard ratio (aHR), 1.04; 95% confidence interval (CI) 0.71-1.51], corticosteroid use (aHR, 0.85; 95% CI, 0.68-1.06) and serious infections (aHR, 0.62; 95% CI, 0.29-1.34) between IFX- and ADA-treated patients; the number of surgical events was very small. On IPTW analysis, risk of corticosteroid use was significantly lower in IFX - as compared to ADA - treated patients (aHR, 0.82; 95% CI, 0.68-0.99). Results were stable on multiple sensitivity analyses.ConclusionsIn a large retrospective cohort of patients with UC who were new users of anti-TNF agents, IFX-treated patients may have lower corticosteroid use than ADA-treated patients, but risk of hospitalisation and serious infections were comparable.
| S-EPMC4917292 | biostudies-literature
Project description:Background and objectivesUlcerative colitis is highly prevalent in Canada and cost-effective ulcerative colitis therapies are warranted. Vedolizumab subcutaneous (SC) formulation was recently approved for ulcerative colitis maintenance therapy. We assessed vedolizumab SC cost effectiveness vs conventional and advanced therapeutics in patients with moderately to severely active ulcerative colitis from a Canadian public healthcare payer perspective.MethodsA hybrid decision tree/Markov model was developed to evaluate vedolizumab SC costs, quality-adjusted life-years, and cost effectiveness vs conventional therapy, adalimumab SC, infliximab intravenous, golimumab SC, tofacitinib, ustekinumab SC, and vedolizumab intravenous. This model predicts the number of patients achieving clinical response and remission after treatment induction, and sustained benefit during maintenance treatment. To account for statistical uncertainties, the base-case analysis was conducted in a probabilistic manner. Scenario analyses examined the impact of previous treatment with anti-tumor necrosis factor agents, dose escalation, loss of efficacy, and treatment adherence.ResultsIn the base-case analysis, conventional therapy was the most cost-effective therapeutic option in the overall population. Vedolizumab SC was cost effective and dominant compared with other advanced therapies (adalimumab, golimumab, infliximab, tofacitinib 5 mg, ustekinumab, and vedolizumab intravenous). The annual vedolizumab SC cost per patient was reduced vs ustekinumab SC, tofacitinib 5 mg, vedolizumab intravenous, and golimumab SC by $47,024, $3251, $2120, and $2004 (Canadian dollars), respectively, and exceeded that of infliximab, adalimumab, and conventional therapy by $582, $3293, and $41,024, respectively. Among the treatments, vedolizumab SC generated the highest quality-adjusted life-years overall (14.21), which translated into the best incremental cost per quality-adjusted life-years gained over conventional therapy in the overall population ($109,374) and in anti-tumor necrosis factor-naïve and anti-tumor necrosis factor-experienced patients ($41,658/$114,287).ConclusionsConventional therapy offered the most cost-effective therapeutic option followed by vedolizumab SC. Based on a $50,000/quality-adjusted life-year threshold, vedolizumab was cost effective in anti-tumor necrosis factor-naïve patients but not the overall population also when compared to conventional therapy.
| S-EPMC9283596 | biostudies-literature
Project description:Inhibitors of tumor necrosis factor (anti-TNF agents) are the most effective therapy for Crohn's disease (CD). We evaluated the real-world comparative effectiveness and safety of different anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) in biologic-naive patients with CD in a retrospective, propensity-matched cohort study using a national administrative claims database (Optum Labs Data Warehouse).We identified 3205 biologic-naive patients with CD (mean age, 41 ± 15 years; 45% male; median follow-up period after anti-TNF therapy, 19 months; 44.5% on infliximab and 38.9% on adalimumab) who received their first prescription for an anti-TNF agent (infliximab, adalimumab, or certolizumab pegol) after a 12-month period without any anti-TNF treatment (baseline), and with a minimum follow-up period of 6 months after their initial anti-TNF prescription, between 2006 and 2014. The primary outcomes were all-cause and CD-related hospitalization, abdominal surgery, corticosteroid use, and serious infections. We performed a propensity-matched, Cox proportional hazards analysis, accounting for baseline demographics, health care use, comorbidities, and use of CD-related medication.Compared with adalimumab-treated patients, infliximab-treated patients had a lower risk of CD-related hospitalization (adjusted hazard ratio [aHR], 0.80; 95% confidence interval [CI], 0.66-0.98), abdominal surgery (aHR, 0.76; 95% CI, 0.58-0.99), and corticosteroid use (aHR, 0.85; 95% CI, 0.75-0.96). Compared with certolizumab pegol-treated patients, infliximab-treated patients had a lower risk of all-cause hospitalization (aHR, 0.70; 95% CI, 0.52-0.95) and CD-related hospitalization (aHR, 0.59; 95% CI, 0.39-0.90). Adalimumab-treated patients had outcomes comparable with those of certolizumab pegol-treated patients. All agents had comparable risk of serious infections.In a retrospective analysis of a large cohort of biologic-naive patients with CD, we found infliximab to be superior to adalimumab and certolizumab pegol for patient-relevant outcomes, without increased risk of serious infections.
| S-EPMC4955682 | biostudies-literature
Project description:IntroductionThe efficacy and safety of vedolizumab, a gut-selective α4β7 integrin antibody, were demonstrated in the GEMINI 1 and GEMINI 2 clinical trials of adults aged 18-80 years. We investigated the efficacy and safety of vedolizumab in patients stratified by age from the GEMINI trials.MethodsSafety and efficacy, including clinical response, clinical remission, and corticosteroid-free remission, at week 6 and/or 52 were determined post hoc in patients aged <35, 35 to <55, and ≥55 years.ResultsAt baseline, 353, 412, and 130 ulcerative colitis (UC) and 582, 443, and 90 Crohn's disease (CD) patients were aged <35, 35 to <55, and ≥55. Of these patients, 56 were aged ≥65 years (UC: 33, CD: 23). Trends favoring vedolizumab over placebo were observed for most efficacy endpoints irrespective of patient age; some variability between subgroups was observed. Safety profiles of vedolizumab and placebo were similar in all age groups. Vedolizumab-treated patients aged ≥55 had the lowest incidence of serious infections (0.9 per 100 person-years) and adverse events leading to hospitalization (14.8 per 100 person-years). There were no age-related differences in the incidence of adverse hematological events, malignancy, or death.ConclusionsThe safety and efficacy of vedolizumab in patients with UC or CD were similar for all age groups. The number of patients in the oldest age group in these analyses was small; thus further studies of vedolizumab in larger cohorts of elderly patients are warranted.FundingMillennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.).
| S-EPMC5331094 | biostudies-literature