Study assesses remission, complication rates with vedolizumab in early, late Crohn's
Patients with Crohn's disease who started vedolizumab within two years of diagnosis were significantly more likely to reach clinical and endoscopic remission than those who had been diagnosed more than two years earlier and already received anti-tumor necrosis factor agents, a manufacturer-supported trial found.
Vedolizumab treatment is safer and more effective in early Crohn's disease than late, according to a new manufacturer-funded study.
To evaluate the ability of vedolizumab to promote clinical, endoscopic, and histological remission in patients with early and late active Crohn's disease over a one-year period, the open-label cohort study, conducted at 22 hospitals in Belgium, Hungary, and the Netherlands from July 2015 to July 2022, included patients who were adults with moderate to severe Crohn's disease. Patients were divided into two groups: early Crohn's disease (defined as a diagnosis less than two years earlier and naive to treatment or only treated with corticosteroids or immunomodulators) and late Crohn's disease (defined as a diagnosis more than two years earlier and previous treatment with corticosteroids, immunomodulators, and anti-tumor necrosis factor agents).
All patients received 300 mg of IV vedolizumab at weeks 0, 2, and 6, then every 8 weeks for 52 weeks, with an additional 300-mg infusion at week 10 if Crohn's Disease Activity Index (CDAI) had not decreased by more than 70 points versus baseline at week 6. Colonoscopies with biopsies were done at screening, week 26, and week 52. The primary endpoint was the proportion of patients with clinical and endoscopic remission (defined as CDAI ≤150 and Simple Endoscopic Score for Crohn's Disease <4) at both week 26 and 52. The study was supported in part by Takeda Nederland, which provided vedolizumab but had no role in study design, use of data, writing of the report, or in the decision to publish. Results were published Oct. 27 by The Lancet Gastroenterology & Hepatology.
Clinical and endoscopic remission at both week 26 and 52 was achieved in 27 (31.4%) of 86 patients with early Crohn's disease versus 15 (8.6%) of 174 patients with late Crohn's disease (difference, 22.8%; 95% CI, 12.6% to 33.7%). Serious adverse events occurred in three (3.5%) patients with early Crohn's disease versus 46 (26.4%) patients with late Crohn's disease. These included infections (1.2% vs. 7.5%), surgery (none vs. 4.6%), intestinal obstruction (none vs. 2.3%), exacerbation of Crohn's disease (1.2% vs. 3.4%), and malignancy (none vs. 1.7%).
Doubling the drug dose after week 26 in patients without an endoscopic response did not lead to higher endoscopic remission rates, the researchers noted. “This finding suggests that the dosing schedule that was originally designed and approved is optimal for most patients and saturates the target. Patients who do not respond most likely have other dominant immune pathways that are activated and remain unaffected by vedolizumab,” they said.
An editorial stated that the study supports the safety and efficacy of the drug, but methodological and definitional challenges, such as inherent differences in previous treatment exposures and differences of timing of diagnosis, complicate interpretation and make direct comparisons difficult. “Although the findings strengthen the evidence for vedolizumab in early Crohn's disease, comprehensive health-economic analyses to support cost versus efficacy in this setting are notably still lacking,” said the editorial, also noting that the cost of the drug is an issue.