Subcutaneous versus intravenous infliximab therapy - a real-world study: toward higher drug concentrations.

Recently, a formula of subcutaneous infliximab (SC-IFX) has been approved for inflammatory bowel disease (IBD), demonstrating a better pharmacokinetic and immunogenic profiles, compared to intravenous infliximab (IV-IFX), with similar efficacy and safety. The aim of this study is to evaluate the clinical, biochemical, and pharmacological outcomes of IBD patients in clinical remission, who switched from IV-IFX to SC-IFX, with a follow-up period of 6 months. Retrospective cohort study, including IBD patients in clinical remission, previously medicated with IV-IFX, who switched to SC-IFX 120 mg every other week. Biochemical parameters were evaluated before the switch and 6 months after, namely infliximab serum concentrations, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin. Included 41 patients in clinical remission, 32 with Crohn's disease (78.0%) and 9 with ulcerative colitis (22.0%). All patients maintained clinical remission during the 6 months after the switch, with a treatment persistence rate of 100%, and no patients requiring corticosteroid therapy, switching back to IV-IFX, or IBD-related hospitalization. The mean infliximab serum concentrations were significantly higher after 6 months of SC-IFX (17.3 ± 6.6 vs. 9.1 ± 5.5 µg/ml, P  < 0.001). However, there were no differences between values of ESR, CRP, and fecal calprotectin, before and after the switch ( P  = 0.791, P  = 0.246, and P  = 0.639). Additionally, none of the patients developed antibodies to infliximab. Switching from IV-IFX to SC-IFX in IBD patients in clinical remission is effective and leads to higher infliximab serum concentrations, regardless of the combination with immunomodulatory therapy.

Ferreira AI ，Lima Capela T ，Arieira C ，Xavier S ，Cotter J ... -  《-》

Higher Serum Infliximab Concentrations Following Subcutaneous Dosing are Associated with Deep Remission in Patients with Inflammatory Bowel Disease.

The relationship between subcutaneous infliximab [SC-IFX] concentrations and favourable therapeutic outcomes in patients with Crohn's disease [CD] and ulcerative colitis [UC] remains elusive. This cross-sectional study included consecutive adult patients with inflammatory bowel disease [IBD] treated with SC-IFX at a maintenance dose of 120 mg/2 weeks. Investigated therapeutic outcomes included sustained clinical remission; composite clinical and biomarker remission [clinical remission and C-reactive protein <5 mg/L]; biochemical remission [faecal calprotectin <250 µg/g]; and deep remission [clinical, biological, and biochemical remission]. Of 91 patients identified, 71 qualified for inclusion in the study [70% with CD; 27% with concomitant immunomodulators]. At the time of drug concentration measurement [median 13.5 months after switch], 55 [77%] patients had sustained clinical remission; n = 44 [62%] composite clinical and biomarker remission; n = 40 [56%] biochemical remission; and n = 31 [43%] deep remission. The mean SC-IFX concentrations were significantly higher in patients with sustained clinical remission [p = 0.014]; composite clinical and biomarker remission [p = 0.003]; biochemical remission [p < 0.001]; and deep remission [p < 0.001] compared to patients without having these outcomes. In multivariate analysis, SC-IFX concentration was the only factor independently associated with sustained clinical remission (odds ratio [OR]: 4.7, 95% confidence interval [CI]: 3.1-12.2, p = 0.005); clinical and biomarker remission [OR: 9.21, 95% CI: 6.09-18.7, p = 0.006]; biochemical remission [OR: 37, 95% CI: 14-39.3, p < 0.001]; and deep remission [OR: 29, 95% CI: 15.7-37.4, p < 0.001]. The optimal SC-IFX concentration cut-off associated with deep remission based on ROC analysis was 20 µg/mL [sensitivity: 0.91, specificity: 0.80, accuracy: 0.85]. Combination with an immunomodulator failed to improve SC-IFX pharmacokinetics. Higher SC-IFX concentrations are associated with higher rates of favourable therapeutic outcomes in IBD patients. Serum SC-IFX concentrations >20 µg/mL were significantly associated with deep remission.

Roblin X ，Nancey S ，Papamichael K ，Duru G ，Flamand M ，Kwiatek S ，Cheifetz A ，Fabien N ，Barrau M ，Paul S ... -  《-》

Effectiveness of switching to subcutaneous infliximab in inflammatory bowel disease patients with inadequate biochemical response during intravenous administration.

Infliximab (IFX) has transformed the management of inflammatory bowel diseases (IBD). While intravenous (IV) IFX has been effective, a subcutaneous (SC) formulation offers advantages in convenience and cost. However, there is lack of evidence regarding the transition from IV to SC-IFX, especially for patients with inadequate responses. This study investigates the effectiveness of switching from IV to SC-IFX in patients with inadequate responses during IV maintenance therapy. A retrospective study enrolled IBD patients who transitioned to SC-IFX after demonstrating inadequate responses during IV maintenance therapy. The study collected data of demographics of patients and dose and therapies administered prior to the IV-IFX. Primary outcomes included improvements in C-reactive protein (CRP) or fecal calprotectin (FC) levels. This study evaluated the trough levels and its differences between pre- and post-switching. Among 44 patients included, 10 exhibited CRP elevation before the switch, with 6 showing normalization post-switch. Similarly, 42 patients had elevated FC levels pre-switch, with 26 experiencing reductions post-switch. Trough levels increased after the switch. However, there were no significant differences between responders and non-responders. This study is the first study to investigate the transition therapy of IV to SC-IFX in patients with inadequate response. This suggests that SC-IFX could be a viable alternative in the management of IBD. However, further research is necessary to evaluate its efficacy in a larger population of patients who exhibit inadequate responses during IV-IFX maintenance therapy.

Lee B ，Kim M ，Kim ER ，Hong SN ，Chang DK ，Kim YH ... -  《Scientific Reports》

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

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 two 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 programme to SC CT-P13 in patients treated with IV infliximab. Patients on established maintenance IV infliximab, who switched to SC CT-P13, were included in this retrospective multicentre cohort study. Disease activity was monitored serially with the Harvey-Bradshaw Index [HBI] for Crohn's disease [CD] and the Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis (UC) for up to 12 months at months 3, 6, and 12. Faecal calprotectin [FC] and C-reactive protein [CRP] were 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 latest follow-up. Secondary outcome measures included infliximab pharmacokinetics [PK], safety, need for corticosteroid rescue therapy, and need for surgery. We included 181 patients, of whom 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: 106, 92.2%; UC: 46, 76.7%; and IBD unclassified [IBD-U]: 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 (13.8%) 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 with baseline]. Among the variables examined, only antibodies to infliximab [ATI] was associated with infliximab levels (odds ratio [OR] -13.369, 95% CI -15.405, -11.333, p <0.001]. A total of 14 patients [7.7%] developed ATI; of these, nine [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 switching, 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. 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.

Smith PJ ，Critchley L ，Storey D ，Gregg B ，Stenson J ，Kneebone A ，Rimmer T ，Burke S ，Hussain S ，Yi Teoh W ，Vazeille S ，Serna S ，Steel A ，Derbyshire E ，Collins P ，Dibb M ，Flanagan P ，Probert C ，Verma AM ，Subramanian S ... -  《-》

An international multicentre study of SwiTching from Intravenous to subcutaneous inflixiMab and vEdolizumab in inflammatory bowel diseases: The TIME study.

Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel diseases (IBDs). Our aim was to evaluate the effectiveness of switching from intravenous (IV) to SC formulations of IFX and VDZ in IBDs. This multicentre, retrospective study collected data of adult patients with Crohn's disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ. The primary endpoint was clinical remission at 12 months stratified based on timing of switch. A composite endpoint consisting of therapy discontinuation, reverse-switch, need for steroids, and drug optimization was evaluated. A multivariate analysis investigated the association between patients' characteristics and outcomes. Two hundred and thirty-one patients (59% UC, 53% male, mean age 44 ± 15 years, 68% IFX) from 13 centres were included. The switch occurred at Week 6 in a third of cases (36%). Median time to switch was 13 months. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (87% and 77%), 6 (86% and 83%) and 12 (63% and 60%) months. In the multivariate analysis, there was no difference in clinical remission rate at 12 months; however, patients switched at Week 6 had a higher rate of experiencing any therapeutic changes at 3 (false discovery rate (FDR) = .002), 6 (FDR <1 × 10-10) or 12 months (FDR = .08). Clinical disease activity at baseline (only in UC) (FDR = .07) and previous exposure to biologics (FDR = .001) were risk factors for composite endpoint at 6 and 12 months. SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching patients in remission reduces the risk of negative outcomes.

D'Amico F ，Massimino L ，Palmieri G ，Dal Buono A ，Gabbiadini R ，Caron B ，Moreira P ，Silva I ，Bosca-Watts M ，Innocenti T ，Dragoni G ，Bezzio C ，Zilli A ，Furfaro F ，Saibeni S ，Chaparro M ，García MJ ，Michalopoulos G ，Viazis N ，Mantzaris GJ ，Ellul P ，Gisbert JP ，Magro F ，Peyrin-Biroulet L ，Armuzzi A ，Ungaro F ，Danese S ，Fiorino G ，Allocca M ... -  《-》