Abstract and Introduction
Background and Aims: Vedolizumab is a gut-selective treatment approved for Crohn's disease (CD) and ulcerative colitis (UC). Recently, a subcutaneous formulation of vedolizumab was approved. The aims of this study were to evaluate efficacy, safety, pharmacokinetics, patient experience and costs following a switch from intravenous to subcutaneous vedolizumab treatment.
Methods: Patients were switched from intravenous to subcutaneous vedolizumab maintenance treatment and followed prospectively for 6 months and a subgroup for 12 months. The primary endpoint was change in faecal calprotectin levels. Furthermore, we evaluated clinical disease activity, remission rates, plasma CRP, drug persistence, adverse events, local injection reactions, serum drug concentrations, patient satisfaction, quality-of-life and treatment costs.
Results: Eighty-nine patients were included (48 CD; 41 UC). Faecal calprotectin decreased significantly in CD but not in UC. Clinical indices, remission rates, plasma CRP levels and quality-of-life scores remained unchanged. Patients that had been on standard compared to optimised IV vedolizumab dosing displayed similar outcomes on standard SC dosing. Drug persistence at 6 and 12 months was 95.5% and 88.5%, respectively. Frequencies of adverse events were similar before and after the switch. No serious adverse events occurred. Transient severe local injection reactions were experienced by 1.2% of patients. Median vedolizumab trough levels were 2.3 times higher on subcutaneous compared to intravenous treatment. Patient satisfaction was generally high. Annualised treatment costs were reduced by 15% following the switch.
Conclusions: The switch from intravenous to subcutaneous vedolizumab could be done with preserved therapeutic effectiveness, safety, high patient satisfaction and low discontinuation rate, at a reduced cost.
The inflammatory process of Crohn's disease (CD) or ulcerative colitis (UC), which are the two main forms of inflammatory bowel disease (IBD), is thought to be driven by the infiltration of dysregulated proinflammatory immune cells into the inflamed intestinal tissue. This infiltration is facilitated by the interaction between the integrin α4β7, which is expressed on several circulating immune cell subsets including previously activated T-cells, and its counterreceptor Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1), which is selectively expressed on the endothelial cells of intestinal venules.
Vedolizumab is a humanised monoclonal IgG1 antibody that binds to α4β7 and inhibits the interaction with MAdCAM-1. This prevents α4β7-expressing immune cells from extravasating which leads to a decrease in local inflammatory activity. More recently, vedolizumab has been shown to modulate innate immunity, including macrophage and dendritic cell populations, in addition to adaptive immunity. The limited expression pattern of MAdCAM-1 is thought to account for vedolizumab's gut-specific immunosuppressive effect which in turn translates into a beneficial safety profile.
Vedolizumab is approved for the treatment of patients with moderate-to-severe CD or UC, where treatment with conventional therapy or an anti-TNF agent has failed. Vedolizumab was originally developed for administration via intravenous (IV) infusions. Recently, a formulation for subcutaneous (SC) administration was approved for maintenance treatment following at least two IV infusions. This approval was based on the phase III trials VISIBLE 1 and VISIBLE 2 which evaluated SC vedolizumab treatment after two initial IV doses in CD and UC patients, respectively.[4,5] The proportion of subjects in clinical remission 52 weeks after the start of treatment, which was the primary endpoint, was significantly higher in the SC vedolizumab-treated group compared to the placebo group, in both trials.[4,5] Median trough concentrations at steady state during SC vedolizumab were 30.2 and 34.6 μg/ml for CD and UC patients, respectively, which was substantially higher than the median trough level during IV treatment presented in VISIBLE 1 (11.1 μg/ml).[4,5] In contrast, the average serum concentrations over time were rather similar (39.8 and 32.2 μg/ml, during SC and IV treatment, respectively).[4,5] Finally, there were no new safety issues observed, other than the incidence of injection-site reaction frequencies.[4,5] However, data on patient experience or satisfaction were not presented in the VISIBLE publications, and studies to investigate the efficacy and safety of switching patients from maintenance IV to maintenance SC vedolizumab treatment in a real-world setting are scarce. To our knowledge, there is only one report on the topic, and in that study, the follow-up time after the switch was only 12 weeks. Given that the half-life of the drug is approximately 26 days and that the wash-out period is several months, such a short follow-up time may not be adequate to examine the effectiveness of the SC formulation. Nevertheless, the authors described a 52% increase (p < 0.01) in the patients' faecal calprotectin levels at the end of their study which was rather unexpected. Thus, further studies are warranted.
There are several potential benefits with SC as compared to IV administration of vedolizumab including a reduced burden of health care resources and increased patient convenience. Potential caveats with SC treatment are increased difficulties to ensure therapy compliance, fewer built-in disease follow-up visits, possible IV treatment preference and local skin reactions to SC injections.
The aims of this study were to assess efficacy, safety, pharmacokinetics, patient experience, patient satisfaction, and potential cost savings following a switch from IV to SC vedolizumab treatment in patients with inflammatory bowel disease in a real-world setting.
Aliment Pharmacol Ther. 2022;55(11):1389-1401. © 2022 Blackwell Publishing