BACKGROUND AND AIMS
Vedolizumab is a fully humanised, monoclonal IgG1 antibody, directed toward α4β7-integrin. It is effective at inducing and maintaining a response in one-third of patients with inflammatory bowel disease (IBD).1 Clinical monitoring for 2 hours is recommended after the two first infusions at Weeks 0 and 2, and for 1 hour after all the subsequent infusions because, as a biotherapy, it may induce an infusion reaction (IR). The occurrence of IR is well described with chimeric monoclonal antibodies (mAb), such as infliximab (IFX).2 In contrast, vedolizumab is a fully humanised mAb and the frequency of IR and immunisation against the drug in studies appears to be low.3-5 However, precise description, time to onset, and severity of acute IR are often lacking in the literature.
METHODS
The authors conducted a multicentre retrospective review of patients with IBD treated with vedolizumab in four French university hospitals. All consecutive patients who received at least one infusion of vedolizumab for ulcerative colitis or Crohn’s disease in one of these four centres from May 2014 until February 2018 were included. Vedolizumab was administrated at a standard dose of 300 mg at Weeks 0, 2, and 6, and then every 8 weeks (or every 4 weeks in cases of treatment optimisation). No patient received premedication before the infusions. The primary outcome was the rate of acute IR, defined by adverse events occurring during the infusion or within 2 hours afterwards. There is no consensus to define acute IR, but because monitoring lasts a maximum of 2 hours, the authors focussed on events that occurred during the course of the infusion or within 2 hours of its completion. IR can be identified by the criteria proposed by Sampson et al.6
RESULTS
A total of 550 patients (260 males; 47%) with a mean age of 43±16 years (range: 17–88) were included. Among them, 299 patients (54%) had Crohn’s disease, of whom 59% had an ileocolonic location and 43% had fistulising disease; and 251 patients (46%) had ulcerative colitis, of whom 58% had pancolitis. At time of vedolizumab initiation, the median duration of IBD was 11 years (range: 1–55). The vast majority of patients received at least one anti-TNF treatment prior to vedolizumab infusion, and of these patients, 367 (67%) received at least two anti-TNF treatments before starting vedolizumab. A total of 6,459 infusions of vedolizumab (average: 12 infusions per patient) were administered during the study period and only six acute IR (0.1%) occurred in the 550 patients. All IR were reported during infusion and five out of six happened during the induction phase of vedolizumab (i.e., the first three infusions). No severe reaction and no anaphylactic shock were registered, athough vedolizumab was definitely discontinued in two cases. The authors performed a univariate analysis using a chi-square test, but they failed to identify risk factors associated with the occurrence of IR. There was a tendency of an increased risk of IR to vedolizumab in patients with a previous history of IR to infliximab, but it was not statistically significant (p=0.07).
CONCLUSION
In this large multicentre cohort, the rate of acute IR was very low, at 0.1%. No severe IR were reported and none of the IR occurred within the 2 hours of recommended monitoring. These data, consistent with the literature, confirm the safety profile of vedolizumab. This therefore allows clinicians to question the need for clinical monitoring after the first two injections of vedolizumab. The withdrawal of this clinical monitoring seems possible in terms of safety, but is also desirable to improve the quality of life of patients with IBD and to reduce the indirect costs of treatment.
