Abstract
Background: Vedolizumab is a gut specific integrin antagonist with established efficacy in inflammatory bowel disease (IBD). Many people with IBD fail to achieve adequate or sustained response to standard dosing, thus requiring dose escalation (DE). We aimed to explore the need for escalated dosing and subsequent outcomes in a large real-world cohort.
Methods: We utilised data from the CCC registry entered during routine clinical care at 14 centres across Australia and New Zealand. Data were extracted in October 2023 and included patients on intravenous (IV) and subcutaneous (SC) therapy. DE was defined as maintenance dosing > 108mg SC fortnightly, > 300mg IV Q8weekly and/or additional induction doses. We examined data prior to and at 12 months post DE.
Results: 919 people with IBD received Vedolizumab, with 28% (n=261) receiving DE therapy. Median age for the DE cohort was 40 years (IQR 29-56) with median age at diagnosis 26 (IQR 19-39). Median age, age at diagnosis, disease duration and BMI did not vary significantly between the DE and standard dosing cohorts. Most of the DE cohort had Crohn’s (60%) followed by ulcerative colitis (38%) and IBD-unclassified (2%). Half the DE cohort was female (49.8%) with median time to dose escalation being 6 months. 57% (n=111) continued on DE Vedolizumab after 12 months.
Median drug level (where measured) increased from 10.3mg/L pre-DE to 19.8mg/L post. Rates of faecal calprotectin (FCP) remission, (FCP <250ug/g) increased at 12 months post DE as did rates of PRO2 and endoscopic remission (p=0.007, 0.034 & 0.016 respectively). Improved remission rates coincided with decreased systemic steroid requirements, which fell by >50% at 12 months post DE (p=0.001). Hospital admissions and radiological investigations were unchanged over the study period, however the need for endoscopic assessment decreased 12 months post DE. Patients receiving DE therapy had increased encounters healthcare providers, with more clinical assessment and Healthline calls at 12 months post DE (p=0.001 & 0.001 respectively).
Conclusion: In an Australasian cohort of people with IBD, over a quarter of individuals receiving Vedolizumab therapy required DE. DE Vedolizumab correlated with improved endoscopic, PRO2 and FCP remission rates at 12 months with reduced steroid use. As biosimilars reduce the cost of DE therapy, further research beyond 12 months examining remission rates, healthcare utilisation and cost analysis in more detail is needed.