Efficacy and Safety of Elective Switching from Intravenous to Subcutaneous Infliximab [CT-P13]: A Multicentre Cohort Study

Abstract

Background Intravenous (IV) infliximab is a well-established therapy for inflammatory bowel diseases (IBD) patients. A subcutaneous (SC) formulation of infliximab (CT-P13) has recently been shown to be as effective as IV infliximab after 2 doses of IV induction in a randomised trial but there are no data to support elective switching of patients on maintenance IV infliximab therapy. We aimed to assess the effectiveness of an elective switching program to SC CT-P13 in patients treated with IV infliximab. Methods Patients on established maintenance IV infliximab who switched to SC CT-P13 were included in this retrospective multi-centre cohort study. Disease activity was monitored serially with Harvey-Bradshaw Index (HBI) for Crohn’s disease (CD) and simple clinical colitis activity index (SCCAI) for up to 12 months at months 3, 6 and 12. Faecal calprotectin (FC) and C-reactive protein (CRP) was recorded at baseline and follow-up, if available. Infliximab trough levels were measured prior to switch and at months 3, 6 and 12 following switch. The primary outcome measure was treatment persistence at last follow-up. Secondary outcome measures included infliximab pharmacokinetics (PK), safety, need for corticosteroid rescue therapy and need for surgery. Results We included 181 patients of who 115 (63.5%) had CD. The majority (72.4%) were on 8-weekly dosing of intravenous infliximab prior to switching and more than half (59.1%) were on concomitant immunomodulatory therapy. The majority of patients (CD: N=106, 92.2%, UC: N=46, 76.7% and IBD-U: N=5, 83.3%) were in clinical remission. Treatment persistence rate was high (N=167, 92.3%) and only 14 patients (7.7%) stopped treatment during the follow-up period. There was no significant difference between baseline and repeat measurements at 3, 6 or 12 months for HBI, SCCAI, CRP or FC. Of the total cohort, 25 patients (21.7%) had perianal CD. Of these, only two patients (8%) had worsening of perianal CD and required antibiotic therapy and further examination under anaesthesia (EUA). Both these patients also switched back to intravenous infliximab. Median infliximab level increased from a baseline of 8.9 µg/dl (range 0.4-16) to 16.0 µg/dl (range 2.3-16, P<0.001) at 3 months. Serum levels stayed stable at 6 months (median 16 µg/dl, range 0.3-17.2) and 12 months (median 16 µg/dl, range 0.3-19.1, both P<0.001 compared to baseline). Among the variables examined, only antibodies to infliximab (ATI) was associated with infliximab levels (OR -13.369, 95% CI -15.405, -11.333, P<0.001). A total of 14 patients (7.7%) developed ATI of which 9 (64.3%) were on concomitant immunomodulatory therapy. Immunomodulatory therapy was not significantly associated with development of ATI (P=0.15). In a subset of patients receiving escalated IV infliximab dosing frequency prior to switch, no difference in treatment persistence was observed in patients receiving weekly versus alternate weekly SC CT-P13. Patient acceptance and satisfaction rates with SC CT-P13 were very high. Conclusions Among patients on IV infliximab maintenance therapy switched to SC CT-P13, we observed high treatment persistence rates and low rates of immunogenicity with no change in clinical disease activity indices or biomarkers. Infliximab levels increased after switch to SC CT-P13 and only ATI was associated with serum infliximab levels. Patient acceptance and satisfaction rates were high with SC CT-P13.

Editorial: intravenous to subcutaneous vedolizumab—switch without glitch!

“…Intriguingly, serum vedolizumab levels increased after switching to SC and this may simply reflect steady‐state drug distribution with the SC formulation as opposed to better bioavailability. Similar findings have been reported in previous cohort studies of switching from IV to SC vedolizumab 8 as well as IV to SC infliximab 9 . Interestingly, previous reports suggest near‐complete occupancy of α4β7 integrin in peripheral blood memory T cells regardless of drug levels 10 and this explains why the increased serum levels with SC vedolizumab may not necessarily translate to better clinical outcomes.…”

“…Similar findings have been reported in previous cohort studies of switching from IV to SC vedolizumab 8 as well as IV to SC infliximab. 9 Interestingly, previous reports suggest near-complete occupancy of α4β7 integrin in peripheral blood memory T cells regardless of drug levels 10 and this explains why the increased serum levels with SC vedolizumab may not necessarily translate to better clinical outcomes. Prospective data on the exposure-efficacy relationship with the SC formulation are required to inform clinicians about optimal vedolizumab concentrations that correlate with efficacy.…”

IBD therapeutics: what is in the pipeline?

“…Treatment persistence, patient acceptance and satisfaction rates with SC CT-P13 were also very high. What is more, patients with perianal CD who were switched from intravenous to SC IFX had high rate of symptom free survival and treatment persistence at 6 months, with comparable efficacy and safety with intravenous Infliximab at 6 months 44 45…”

Subcutaneous Infliximab [CT-P13], a True Biologic 2.0. Real Clinical Practice Multicentre Study

“…However, we need evidence from clinical practice to reaffirm these results. To date, only one study has been published in manuscript form that evaluated the persistence of treatment, as well as the pharmacokinetic data of subcutaneous infliximab [ 11 ]. The manuscript by Smith et al is a retrospective multicenter cohort study, which included stable patients who received treatment with IV infliximab and who were switched to SC CT-P13.…”

“…In addition, no changes were observed in disease clinical activity indices or in biomarkers. As in the pivotal study, infliximab levels increased after switching to SC CT-P13, and only the presence of antibodies was associated with serum infliximab levels [ 11 ].…”