Vedolizumab Long-Term Treatment Persistence and Safety - Results From a Multinational Extended Access Program Study

Introduction: Vedolizumab (VDZ) is a gut-selective humanised monoclonal anti-α4β7 integrin antibody for treatment of ulcerative colitis (UC) and Crohn’s disease (CD). The GEMINI Long-Term Safety (LTS) study demonstrated the durable efficacy and safety of VDZ for inflammatory bowel disease (IBD) treatment. Patients (pts) experiencing clinical benefit from VDZ in GEMINI LTS or VERSIFY studies could continue treatment in the VDZ extended access programme (XAP). Methods: The XAP study was a phase 3b/4, prospective, open-label, multinational, interventional study (NCT02743806) conducted from Aug 2016 to Jan 2023 to investigate long-term treatment persistence and safety of VDZ 300mg IV every 4 weeks (Q4W) or every 8 weeks (Q8W) in adults with UC or CD. Results: 331 pts (UC=142; CD=189) were enrolled (VERSIFY=20; GEMINI LTS=311). Pts treated with VDZ in XAP had either dose frequency reduction Q4W to Q8W or were maintained on current Q8W or Q4W dosing; 297 started XAP on Q8W dosing, of which 295 received ≥1 VDZ dose in XAP. At XAP baseline, mean (SD) disease duration was UC: 13.9 (6.8) and CD: 13.2 (6.8) yrs; most pts were in clinical remission (Table 1). 283/295 pts (95.9%) were persistent on Q8W dosing for ≥6 months without relapse UC: 129/132 (97.7%) and CD: 154/163 (94.5%). Median (range) duration of VDZ treatment in XAP was UC: 3.8 (0–6) and CD: 4.2 (0–6) yrs. Only 27 pts (9.2%) were re-escalated from Q8W to Q4W dosing (UC: 11/132 [8.3%] and CD: 16/163 [9.8%]); median (range) duration from last dose in the qualifying study to dose escalation in XAP was UC: 1.5 (0.6-3.0) and CD: 1.2 (0.2–5.2) yrs; the corresponding duration from last dose in the qualifying study to relapse was 1.4 (0.4–4.0) and 1.2 (0.06–5.4) yrs. Adverse events (AEs) after enrolment into XAP occurred in 61.3% of pts with UC and 62.4% with CD (treatment-related in 2.1% UC and 4.2% CD), only 4.2% UC and 1.6% CD had AEs leading to study discontinuation (treatment-related: 0.7% UC, 0.5% CD); 13.4% UC and 16.4% CD had serious AEs (treatment-related: 0.7% UC, 0.5% CD). Severe infections occurred in 2 pts with UC (1.4% including 1 with COVID-19) and in 1 pt with CD (0.6%), none were considered treatment-related. There was 1 death from COPD. Conclusion: This long-term, prospective study reported high pt persistence on VDZ Q8W after the reduction of dosing frequency, together with low rates of dose frequency escalation to Q4W and relapse. Safety results were consistent with the known safety profile of VDZ; no new safety signal was identified. Table 1. - Baseline Patient Characteristics Parameter UCVDZ N=142 from GEMINI LTS CDVDZ N=169 from GEMINI LTS, N=20 from VERSIFY Dose frequency reduction to Q8W (N=121) Dose frequency escalation to Q4W (N=10) Q4W Maintenance (N=8) Total (N=142)a Dose frequency reduction to Q8W (N=128) Dose frequency escalation to Q4W (N=14) Q4W Maintenance (N=26) VERSIFY Q8W Maintenance (N=20) Total (N=189)b Age, mean (SD), years 47.0 (11.6) 46.2 (10.7) 55.1 (13.6) 47.7 (11.8) 42.6 (11.8) 37.7 (5.70) 44.6 (13.8) 38.4 (14.6) 42.1 (12.1) Clinical remission, n (%) 118 (97.5) 8 (80.0) 5 (62.5) 133 (93.7) 118 (92.2) 13 (92.9) 19 (73.1) 15 (75.0) 166 (87.8) Partial Mayo score, mean (SD) 0.4 (0.9) 0.9 (1.3) 1.3 (1.8) 0.5 (1.0) NA NA NA NA NA Harvey Bradshaw Index score, mean (SD) NA NA NA NA 1.3 (2.1) 1.8 (1.6) 3.3 (2.8) - 1.7 (2.3) Prior anti-TNFα therapy, n (%) 22 (18.2) 4 (40.0) 2 (25.0) 28 (19.7) 41 (32.0) 8 (57.1) 13 (50.0) 11 (55.0) 73 (38.6) Concomitant medications, n (%) CS 5 (4.1) 1 (10.0) 0 6 (4.2) 6 (4.7) 1 (7.1) 1 (3.8) 4 (20.0) 12 (6.3) CS + IMM 2 (1.7) 0 0 2 (1.4) 2 (1.6) 0 0 0 2 (1.1) IMM 24 (19.8) 1 (10.0) 3 (37.5) 29 (20.4) 28 (21.9) 5 (35.7) 4 (15.4) 8 (40.0) 45 (23.8) aIncludes 3 patients who had multiple dose changes.bIncludes 1 patient from GEMINI LTS who had multiple dose changes.