P0797 Clinical outcomes of dose escalated vedolizumab in Inflammatory Bowel Disease: a retrospective tertiary centre experience
Authors: Gondal F , Salehi O , Terlato M , Pillay L , Macrae F , Rentsch C , Dimovski S , Segal J P 
Published: January 2025

Abstract

Background
Dose escalation has emerged as a key strategy in optimising the effectiveness of biologic therapies in patients with inflammatory bowel disease (IBD) facing secondary loss of response (SLOR). Emerging data supports dose escalation of anti-tumour necrosis factor α (TNF-α) biologics, with many centres employing the use of therapeutic drug monitoring (TDM) guided by serum drug levels 1. However, titration of vedoluzimab remains challenging due to the lack of available TDM 2. The effectiveness and safety of dose escalated vedolizumab is an area of ongoing interest, particularly, with vedolizumab perhaps being a safer alternative in patients who warrant avoidance of systemic immunosuppression 3. As such, we evaluated clinical outcomes of dose escalated vedolizumab at a large tertiary centre.

Methods
We performed a retrospective analysis of IBD patients receiving dose escalated vedolizumab from 2016 to 2024 at the Royal Melbourne Hospital. Dose escalation was defined as an increase of dose (&gt;300mg) and/or frequency [every 8 weeks (&gt;Q8W)] and/or received additional induction doses. We reported primary outcomes as treatment persistence, clinical disease status (SCCAI & HBI) and biochemical markers (faecal calprotectin & CRP), at the following intervals: 3-12 months, 12 months, and yearly up to 36 months following escalation. Secondary outcomes include hospitalisation and surgery rates.

Results
Of the 16 patients (median age 43.5, 56% female) who had previously received dose escalated vedolizumab, 12 had ulcerative colitis (UC) and 4 had Crohn’s disease (CD). Indications for dose escalation included: sonographic features of disease progression on intestinal ultrasound (18.8%), concerning endoscopic findings (6.3%) and clinical loss of response (75%). Dose escalation led to significant improvements in UC activity scores (Simple Clinical Colitis Activity Index (SCCAI): p=0.043), but not CD activity scores (Harvey-Bradshaw Index (HBI): p&gt;0.05), at 3-12 months respectively. Dose escalation did not yield statistically significant reductions in CRP and faecal calprotectin (p &gt; 0.05) at all measured time points. Patients previously exposed to biologics had higher persistence at 36 months compared to biologic naïve patients – at 69% and 50% respectively. Surgery was required in 0% of patients, although 25% of patients (n=4) had prior bowel resections, and 6.25% required hospitalisation (n=1). No serious adverse reactions were reported in any followed up patients.

Conclusion
Dose escalation of vedolizumab appears to be safe and effective in IBD patients with secondary loss of response. Our study demonstrates that dose escalation prolongs treatment persistence and improves patient quality of life.

References
1.Papamichael K, Cheifetz AS. Therapeutic Drug Monitoring and Safety of Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Disease. Clinical Gastroenterology and Hepatology. 2021;19(4):854-855.
2.Ward MG, Sparrow MP, Roblin X. Therapeutic drug monitoring of vedolizumab in inflammatory bowel disease: current data and future directions. Therapeutic Advances in Gastroenterology. 2018;11:175628481877278.
3.Bye WA, Jairath V, Travis SPL. Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease. Alimentary Pharmacology & Therapeutics. 2017;46(1):3-15. doi:https://doi.org/10.1111/apt.14075