Introduction

Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking drug indicated for the treatment of CD and UC [1] administered by intravenous (IV) infusion at Weeks 0, 2, and 6 followed by IV infusions every 8 weeks (Q8W) or subcutaneous injections every 2 weeks [2,3]. For IV treated patients who experience a suboptimal or loss of response (LOR), dose escalation to every four-week infusions (Q4W) may recapture response to treatment [4] but there is a lack of large-scale real-world data describing outcomes of dose-escalated patients [5].

Aims & Methods

Patients with moderately to severely active UC or CD were prospectively followed in a patient support program in Canada from 2015 to 2023. Harvey-Bradshaw Index (HBI, CD) and Partial Mayo Scores (PMS, UC) were assessed 2, 6, and 14 weeks after treatment initiation to understand VDZ induction effectiveness. HBI or PMS were assessed 12 weeks post dose Q4W escalation to understand the effectiveness of dose escalation in the presence of suboptimal or LOR. Results are presented for patients who dose escalated to Q4W from Q8W maintenance (Q8W > Q4W), initiated Q4W at week 14 (w14>Q4W), or at week 10 (w10>Q4W). Remission was defined as HBI <5, or PMS <3. Response was defined as achieving remission or an HBI decrease of ≥3 points from baseline, or a PMS decrease of ≥2 points and ≥25% from baseline.

Results

1056 CD (45% bio-naïve) patients and 1959 UC patients (71% bio-naïve) were eligible for this study. The median follow up was 18 months (range 3-61). The median age was 48 years (range: 18-92), and 44 years (range:18-89) for CD and UC patients respectively. 60% of CD patients and 51% of UC patients were female. For CD patients the median baseline HBI score was 10 (range 8-40), and for UC patients the median baseline PMS score was 6 (range 5-20). Disease duration prior to VDZ was longer in bio-experienced patients compared to bio-naïve; CD (Medians: 14 vs 4 years) and UC (Medians: 6 vs 4 years). To further characterise the patient cohort induction effectiveness is reported. For CD patients, remission and response were 25% and 56% at 2 weeks, 34% and 66% at 6 weeks and 40% and 68% at 14 weeks. For UC patients, remission and response were 32% and 64% at 2 weeks, 48% and 78% at 6 weeks and 55% and 81% at 14 weeks. In CD, 39% (183 of 473) of bio-naïve patients and 52% (302 of 583) of bio-experienced patients dose-escalated to Q4W within the first two years. In UC, 37% (520 of 1399) of bio-naïve patients and 49% (275 of 560) of bio-experienced patients dose-escalated to Q4W within the first two years. At Q4W dose escalation, 319 CD patients (110 bio-naïve, 209 bio-experienced) and 514 UC patients (334 bio-naïve, 180 bio-experienced) were not in HBI or PMS remission. For these patients, remission and response 12-weeks post dose escalation to Q4W are presented in table 1.

Table 1: 12-week remission and response rates for pts dose escalated to Q4W from maintenance (Q8W>Q4W), at week 14 (W14>Q4W) or at week 10 (W10>Q4W)

Conclusion

Conclusion: IBD patients experienced clinically meaningful remission and response rates following induction with IV VDZ. For those that have a suboptimal or LOR this study demonstrates the real-world effectiveness of dose escalating VDZ to Q4W in Canadian patients with IBD to complement previous clinical trials, and real-world studies.

References

1. Argollo, M., et al., Novel therapeutic targets for inflammatory bowel disease. J Autoimmun, 2017. 85: p. 103-116.
2. Sandborn, W.J., et al., Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med, 2013. 369(8): p. 711-21.
3. Feagan, B.G., et al., Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med, 2013. 369(8): p. 699-710.
4. Varghese, D., et al., P632 Vedolizumab dose escalation in patients with inflammatory bowel disease experiencing loss of response: A systematic review and meta-analysis of real-world evidence. Journal of Crohn's and Colitis, 2020. 14(Supplement_1): p. S524-S525.
5. Peyrin-Biroulet, L., et al., Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn's Disease or Ulcerative Colitis: A Systematic Review and Meta-analysis.

Disclosure

Jessica Weiss - Employee of Pentavere Research Group Inc.
Dr. Christopher Pettengell - Employee of Pentavere Research Group Inc.
Dr. Jean-Frédéric LeBlanc - AbbVie, BMS, Janssen, Frenesius-Kabi, Pfizer, Sandoz, Takeda.
Dr. Edmond-Jean Bernard - Fees of SICLEO for my presentations, Participation in advisory boards or speaker services: Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, Eli Lilly, BMS, Grant/Research:Janssen, Abbvie, Any other investment or relationship that could be judged by a reasonable and knowledgeable participant to have the potential to influence the content of the training activity: Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, BMS
Dr. Brian Bressler: Advisor/Speaker: Ferring, Janssen, Abbvie, Takeda, Pfizer, BMS, Merck, Sandoz, Organon, Lifelabs, Celltrion. Advisor: Alimentiv, Gilead, Iterative Health, AMT, Celgene, Merck, Amgen, Pendopharm, Eli Lilly, BMS, Fresenius Kabi, Mylan, Viatris, Bausch Health, Celltrion Healthcare, BioJamp Pharma, Eupraxia. Research support: Janssen, Abbvie, GSK, BMS, Amgen, Genentech, Merck. Stock Options: Qu Biologic
Dr. A. Hillary Steinhart: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris,Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda,Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda
Dr. Ryan Ward - Employee of Takeda
Abhinav Wadhwa - Employee of Takeda