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* = Presenting author

P263. Long-term clinical experience with vedolizumab for the treatment of inflammatory bowel disease: A phase 2 open-label safety extension study

A. Parikh1, T. Leach1, I. Fox1, J. Xu1, M. Patella1, B. Feagan2,3

1Millennium Pharmaceuticals, Cambridge, MA, United States; 2Robarts Research Institute, London, ON, Canada; 3University of Western Ontario, London, ON, Canada

Background: Vedolizumab (previous versions MLN0002, MLN02, LDP-02) is a gut-selective, anti-inflammatory monoclonal antibody in phase 3 development for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). Vedolizumab binds to α4β7 integrin, antagonizing its interaction with MAdCAM-1 and thereby interfering with migration of gut-homing leukocytes. We report a long-term clinical experience with vedolizumab for mild to moderate UC and moderate to severe CD.

Methods: This was an extension of an earlier placebo-controlled, PK/PD/safety study. Upon completing that study, 38 UC patients (rollovers) were randomized to a loading regimen of vedolizumab 2, 6 or 10 mg/kg on Days 1, 15 and 43, followed by maintenance dosing every 8 weeks. In addition, 15 and 19 vedolizumab-naïve patients with UC and CD, respectively, were randomized to vedolizumab 2, 6 or 10 mg/kg dosed on the same schedule. Patients were treated for ≤21 months. Eligible patients were 18–75 years old with partial Mayo scores (PMS) of 0–7 (UC) or CDAI of 220–450. (Vedolizumab-naïve patients had PMS of 2–7.) Permitted concomitant medications included 5-ASA, prednisone (≤30 mg/day) and AZA/6-MP (CD patients only). Safety, efficacy (partial Mayo scores, CDAI, IBDQ), and laboratory parameters were assessed on Days 1, 43, 99, 155, 267, 379, 491 and 637.

Results: Overall, 42 of 72 patients (58.3%; UC = 38/53, CD = 4/19) achieved clinical remission by Day 491.

 BaselineDay 491
Patient Group, MeasureNMean ± SDNMean ± SD
UC total, PMS533.2±2.5430.8±1.2
UC Rollovers382.3±2.2360.8±1.3
UC Vedolizumab-naïve155.4±1.970.9±0.4
CD, CDAI19295±6410190±89
All, IBDQ72151.9±38.153186.8±29.6
All, CRP (mg/L)688.0±14.9383.7±4.8*
*Day 267.

52/72 patients (72%) completed this study. 13 patients were treated for 0–6 months; 5, for 7–12 months; 21, for 13–18 months; 33, for >18 months. Reasons for discontinuation were lack of response (n = 11), adverse events (n = 7), and withdrawal of consent (n = 2). 56 patients (78%) experienced ≥1 adverse event (AE); 10 (14%) reported ≥1 serious AE. The most common AEs (≥4% of patients) were nasopharyngitis (17%); headache (13%); cough (8%); arthralgia, CD exacerbation, influenza (6% each); nausea, URI, viral infection and vomiting (4% each). No systemic opportunistic infections were reported, including PML. After Day 491, one CD patient developed Salmonella gastroenteritis with bacteremia, which responded to antibiotics.

Conclusion: Mean disease activity indices and IBDQ scores indicate clinical benefit of vedolizumab in active IBD. Baseline disease activity likely accounts for the higher remission rates of the UC versus CD patients. Vedolizumab was well tolerated.