ODESSA-UC Study Compares Dose Escalation in Vedolizumab, AntiTNF-α for Ulcerative Colitis

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Patients with ulcerative colitis (UC) treated with vedolizumab experience decreased rates of dose escalation, lower costs, and fewer adverse outcomes compared to those receiving antitumor necrosis factor-alpha treatment, according to findings from the ODESSA-UC study.

A greater proportion of patients treated with adalimumab and infliximab received dose escalation than patients treated with vedolizumab, with further analysis revealing treatment with vedolizumab was associated with a significantly lower likelihood of dose escalation.¹

“Real-world studies that compare the frequency of dose escalation in biologic-naïve patients with UC receiving anti–TNF-α treatments or vedolizumab are lacking. In addition, there are limited data on adverse events and economic outcomes after dose escalation, as well as the time to dose escalation,” wrote investigators.¹ “Such data may enhance stakeholders’ understanding of the clinical implications of dose escalation and associated healthcare resource use.”

For patients with moderate to severe UC, biologics can calm inflammation and provide symptom relief by targeting proteins made by the immune system. Although antitumor necrosis factor-alpha treatment has shown success as a first-line biologic treatment, primary nonresponse and loss of response impact its effectiveness in some patients and may require dose escalation.² An α4β7 integrin inhibitor, vedolizumab offers an alternative biologic treatment option for patients with UC. However, little is known about the frequency of dose escalation in either treatment in a real-world setting.³

To assess dose escalation and associated outcomes and costs in biologic-naïve patients with UC, Sabyasachi Ghosh, MS, of Takeda Pharmaceuticals, and a team of investigators collected administrative claims data from IBM MarketScan databases for adult patients with ≥1 claim for adalimumab, infliximab, or vedolizumab. For inclusion, patients were required to have ≥ 2 claims at least 10 days apart for UC or Crohn disease with ≥ 1 claim on or before index date 1, defined as the date of the first medical/pharmacy claim for a qualifying biologic. Continuous enrollment of 6 months before and 6 months after index date 1 with pharmacy benefit coverage and at least 60% of days covered during the first 6 months after index date 1 were also required for inclusion.¹

Investigators identified and enrolled 1857 eligible patients in the study. Among the cohort, 421 (22.7%) patients received vedolizumab, 688 (37.0%) received infliximab, and 748 (40.3%) received adalimumab. Investigators noted treatment groups had similar demographics, including age, sex, and US region.¹

While index date 1 was the date of the first medical/pharmacy claim for a qualifying biologic, index date 2 was defined as the date of the first medical/pharmacy claim in the maintenance phase. Index date 3 was defined as the date of dose escalation among patients whose dose was escalated, defined as an increase of at least 20% in the average daily dose relative to the expected daily dose based on the approved prescribing information for UC.¹

The primary objective was to compare the proportions of patients whose dose was escalated across biologic treatment groups in the first 6 and 12 months after the start of maintenance treatment and over the entire maintenance period. Exploratory objectives included comparing the hazard rate of dose escalation for vedolizumab with anti–TNF-α treatments in the 12 months after the initiation of maintenance dosing and comparing adverse outcomes and costs after dose escalation across treatment groups.¹

Upon analysis, the proportion of patients whose dose was escalated after the initiation of maintenance treatment was lower for vedolizumab than for infliximab or adalimumab at all time points evaluated. After adjustment for baseline demographics and clinical characteristics, the risk of dose escalation was significantly greater for infliximab (hazard ratio [HR], 1.894; P < .0001) and adalimumab (HR, 2.120; P < .0001) than for vedolizumab.¹

Investigators noted the time to dose escalation was significantly longer for vedolizumab than for adalimumab and infliximab (P < .0001). The HR for time to dose escalation was 2.16 (95% Confidence interval [CI], 1.72–2.71) for adalimumab and 1.90 (95% CI, 1.51–2.41) for infliximab, relative to vedolizumab.¹

After adjusting for covariates, the odds of experiencing infection, sepsis, or IBD-related hospitalization after dose escalation were 2 times higher for those who received adalimumab or infliximab than for those who received vedolizumab (Odds ratio [OR], 2.052; 95% CI, 1.200–3.507; P = .009). Additionally, the odds of corticosteroid use after dose escalation were greater among those who received an anti–TNF-α treatment than for vedolizumab (OR, 1.967; 95% CI, 1.467–2.638; P < .0001).¹

Investigators pointed out unweighted mean index drug costs following dose escalation were lowest for vedolizumab ($14,045.44; Standard deviation [SD], $34,871.70), followed by infliximab ($22,284.67; SD, $50,525.93) and adalimumab ($39,139.10; SD, $67,453.71). Patients who received an anti–TNF-α treatment were more than 2 times more likely to incur an index drug cost after dose escalation than those who received vedolizumab (OR, 2.295; 95% CI, 1.771–2.975; P < .0001). Among patients whose dose was escalated, expected index drug costs were significantly greater for those who received an anti–TNF-α treatment than for those who received vedolizumab (ratio of expected cost, 1.245; 95% CI, 1.029–1.506; P = .025).¹

“Our real-world study in patients with UC demonstrated differences in the rates of dose escalation, subsequent adverse outcomes, and economic outcomes among first-line biologic therapies, favoring vedolizumab over infliximab and adalimumab,” concluded investigators.¹

References:

1. Sabyasachi G, Niranjan K, Kandavadivu U, et al. Dose Escalation of Biologics in Biologic-Naïve Patients With Ulcerative Colitis: Outcomes From the ODESSA-UC Study, Crohn's & Colitis 360. October 2023. https://doi.org/10.1093/crocol/otad061
2. Marsal J, Barreiro-de Acosta M, Blumenstein I, et al. Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease. Front Med (Lausanne). 2022;9:897936. Published 2022 Jun 15. doi:10.3389/fmed.2022.897936
3. Park SC, Jeen YT. Anti-integrin therapy for inflammatory bowel disease. World J Gastroenterol. 2018;24(17):1868-1880. doi:10.3748/wjg.v24.i17.1868