P-098 Effects of Increased Vedolizumab Dosing Frequency on Clinical Remission and Response in Ulcerative Colitis and Crohnʼs Disease

Abstract

BACKGROUND: Vedolizumab (VDZ) was efficacious and safe in the GEMINI 11 and 22 studies of patients with ulcerative colitis (UC) and Crohn's disease (CD), respectively. In a long-term extension study (GEMINI LTS; ClinicalTrials.gov No. NCT00790933), we evaluated the effects of an increase in VDZ dosing frequency from every 8 weeks (Q8W) to every 4 weeks (Q4W) among patients who had lost response to VDZ Q8W during GEMINI 1 or 2. METHODS: Patients in the randomized, placebo-controlled GEMINI 1 and 2 studies who responded to VDZ 300 mg during the 6-week induction phase but later discontinued the 46-week maintenance phase for lack of efficacy on VDZ 300 mg Q8W were among those eligible to receive open-label VDZ 300 mg Q4W in GEMINI LTS. Percentages of these patients in clinical remission (UC, partial Mayo Clinic [pMC] score <2 with no individual subscore >1; CD, Harvey-Bradshaw Index [HBI] score <4) and with a clinical response (UC, pMC score decrease of >2 and >25% from baseline with rectal bleeding subscore decrease of >1 from baseline or absolute rectal bleeding subscore <1; CD, HBI score decrease of >3 from baseline) were evaluated. These end points were also evaluated among subgroups of patients with and without prior tumor necrosis factor (TNF) antagonist failure. Average VDZ concentrations at week 52 for patients who discontinued GEMINI 1 or 2 were predicted to standardize pharmacokinetic data at the same time point relative to study entry.3 These concentrations were compared with those predicted for GEMINI 1 or 2 completers. RESULTS: Among patients treated with VDZ Q8W in GEMINI 1 (n = 122) and GEMINI 2 (n = 154), 32 (26%) and 57 (37%), respectively, discontinued for lack of efficacy and entered GEMINI LTS to receive VDZ Q4W. After this increase in dosing frequency, clinical remission and response rates increased and were generally maintained through week 52 of GEMINI LTS (Tables 1 and 2) Median predicted average VDZ concentrations at week 52 were slightly higher in patients receiving VDZ Q8W who completed the studies (UC: 36.9 mg/mL, n = 75; CD: 39.5 mg/mL, n = 74) than in those who discontinued (UC: 30.5 mg/mL, n = 32; CD: 32.7 mg/mL, n = 57). Adverse event profiles were similar between the Q8W and Q4W regimens in GEMINI 1 and 21,2 CONCLUSIONS: Percentages of clinical remission and response increased after VDZ dosing frequency was increased to Q4W for patients with UC or CD who had lost response to VDZ Q8W. Average VDZ concentrations at week 52 were predicted to be only slightly lower in these patients than in patients treated with VDZ Q8W who completed GEMINI 1 or 2. These uncontrolled data may help support the utility of VDZ Q4W dosing. (Table Presented).