Abstract and Introduction
Background: Subcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions.
Aim: To assess the effectiveness, safety and pharmacokinetics of a switch from intravenous (IV) to SC maintenance vedolizumab in patients with IBD
Methods: In this prospective cohort study, patients with IBD who had ≥4 months IV vedolizumab were switched to SC vedolizumab. We studied the time to discontinuation of SC vedolizumab, adverse events (AEs), changes in clinical and biochemical outcomes and vedolizumab concentrations at baseline, and weeks 12 and 24.
Results: We included 82 patients with Crohn's disease (CD) and 53 with ulcerative colitis (UC). Eleven (13.4%) patients with CD and five (9.4%) with UC discontinued SC vedolizumab after a median of 18 (IQR 8–22) and 6 weeks (IQR 5–10), respectively. Four patients with CD switched to a different drug due to loss of response, nine switched back to IV vedolizumab due to adverse events, and three due to needle fear. Common AEs were injection site reactions (n = 15) and headache (n = 6). Median clinical and biochemical disease activity remained stable after the switch. Median serum vedolizumab concentrations increased from 19 μg/ml at the time of the switch to 31 μg/ml 12 weeks after the switch (p < 0.005).
Conclusions: Switching from IV to SC vedolizumab maintenance treatment is effective in patients with CD or UC. However, 9% of patients were switched back to IV vedolizumab due to adverse events or fear of needles.
Vedolizumab (VDZ) is a gut-selective, humanised monoclonal antibody directed towards α4β7 integrins, preventing their trafficking into the inflamed gut and possibly modulating the innate immunity.[1,2] Since 2014, VDZ has been registered for the treatment of patients with moderate to severe inflammatory bowel disease (IBD).[3,4] VDZ is typically administered intravenously (IV). Recently, two phase 3 trials (VISIBLE 1 and 2) demonstrated that a subcutaneous (SC) formulation of VDZ is effective and safe for patients with ulcerative colitis (UC) and Crohn's Disease (CD) directly after induction treatment with two infusions of VDZ.[5,6] These trials showed that in IBD patients who responded at week 6, 108 mg maintenance SC VDZ was superior to placebo for the primary endpoint of clinical and biochemical remission. Based on these trials, SC VDZ (Entyvio©) was approved by the European Medicines Agency as maintenance treatment in adult patients with moderate-to-severe active UC or CD in 2020. However, the VISIBLE 1 and 2 trials did not study IBD patients who have been treated with maintenance IV VDZ for a longer time. Therefore, we aim to prospectively follow IBD patients who are treated with maintenance IV VDZ for a longer period in a real-world setting.
SC and IV formulations in general have different pharmacokinetic profiles. SC administration leads to gradual absorption, incomplete bioavailability and lower peak concentrations.[7,8] VDZ infusion results in immediate systemic drug exposure and a high initial peak concentration. In the VISIBLE 1 trial, UC patients in the SC VDZ treatment group had higher VDZ serum trough concentrations when compared to the IV VDZ treatment group. However, the overall average drug exposure was similar upon 108 mg SC VDZ every 2 weeks versus 300 mg IV VDZ every 8 weeks. As previous studies found an association between favourable therapeutic outcomes and high VDZ serum concentrations during IV maintenance treatment,[9–12] these high VDZ serum trough concentrations and stable systemic drug exposure using SC VDZ treatment may improve efficacy outcomes.
The option of a SC formulation of VDZ offers patients a choice regarding the route of administration. Previous studies evaluating patient preferences patient preference between SC and IV treatment is variable.[13,14] However, SC treatment might reduce direct health care costs (no infusion unit necessary), societal costs (no need to take time off work and for most patients to travel to infusion location) and environmental costs (no traffic to the hospital).[15,16]
In this study, we assessed drug discontinuation, effectiveness, safety and pharmacokinetics in a prospective real-world cohort of CD and UC patients, who switched from IV VDZ maintenance treatment to SC VDZ.
Aliment Pharmacol Ther. 2022;56(6):1044-1054. © 2022 Blackwell Publishing