Impact of proactive of infliximab monitoring using the Bayesian approach in the maintenance phase in patients with inflammatory bowel disease

Background and objectivesThere is increasing evidence that proactive monitoring is useful in improving the control of inflammatory bowel disease, although it remains controversial. The aim of this study was to evaluate the efficacy of proactive TDM based on the Bayesian approach to optimise the IFX dose compared with the standard of care dosing in patients with IBD.MethodsRetrospective observational cohort of inflammatory bowel disease patients > 18 years. Patients were classified into two groups according to the strategy used to optimise the dose of IFX: a standard therapy group (ST-group) with clinically based dose adjustment and therapeutic drug monitoring group (TDM-group), with estimation of pharmacokinetic parameters calculated by Bayesian prediction.ResultsA total of 153 patients were included. Of these, 75 were in the TDM-group. Clinical response at week 52 was evaluated in 114 patients. The proportion of patients who achieved clinical remission was higher in the TDM than in the ST-group (80.7% vs 61.4%, respectively, p = 0.023). A total of 28 patients (24.6%) met the parameters for the composite variable ‘poor clinical outcome’ at week 52. The proportion of patients who reached this outcome was lower in the TDM-group than in the ST-group (12.3% vs 36.8%, respectively, p = 0.002).ConclusionsProactive therapeutic drug monitoring using Bayesian approach is associated with higher secondary response and fewer long-term complications.     

Crohn’s disease with infliximab treatment complicated by rapidly progressing colorectal cancer: A case report

BACKGROUNDCrohn''s disease (CD) causes a range of digestive symptoms including recurrent diarrhea, abdominalgia, and flatulence, and severely impacts the quality of life of patients. Infliximab, a monoclonal antibody against tumor necrosis factor alpha, has recently been promoted as a therapeutic treatment for CD, but its safety margins remain uncertain. We report a case of rapidly progressive colorectal cancer that was diagnosed in a patient with CD who had previously been treated with infliximab.CASE SUMMARYThis case report refers to a 40-year-old male with a 6-year history of CD. The patient underwent transverse colostomy because of inflammatory ileus in 2017. He subsequently received infliximab treatment in 2018. Ten months later, worsening contracture of the transverse colostomy was observed. Imaging tests indicated that the patient may have developed colon cancer with extensive peritoneal implantation. At the same time, colonoscopy revealed a rectal mass and pathological examination indicated well-differentiated adenocarcinoma. Palliative ileostomy was performed to improve defecation in 2019. During the operation, a small nodular mass in the mesentery of the small intestine was identified and pathological examination of the mass revealed advanced adenocarcinoma. The patient was diagnosed with advanced colorectal cancer and administered palliative chemotherapy. He died in June 2020.CONCLUSIONWe stress the importance of recognizing the possible occurrence of malignance in patients with CD receiving infliximab.     

An in vitro comparison of four different immunoassays for the monitoring of Infliximab biosimilars drug levels

BackgroundSB2 (Renflexis®, Merck) and CT-P13 (Inflectra®, Pfizer) are biosimilars of the reference Infliximab (Remicade®, Janssen) and are approved in Canada for use in indications for which Infliximab is approved, including inflammatory bowel disease. These biosimilars are structurally different but exhibit comparable physicochemical characteristics, pharmaceutical effectiveness and immunogenicity compared to Infliximab. Optimal Infliximab therapy currently relies on therapeutic drug monitoring offered by several reference laboratories.ObjectiveBecause the appropriate dosing depends on accurate determination of drug levels and anti-drug antibodies, the ability of current Infliximab assays to measure the biosimilars and corresponding antibodies needs to be demonstrated.MethodsThe correlation between Infliximab and the biosimilars measured with four different enzyme-linked immunosorbent assays for Infliximab detection was evaluated. Spiked serum samples were assayed with kits from (A) Immunodiagnostik/ALPCO Diagnostics, (B) R-Biopharm, (C) Theradiag and (D) Progenika Biopharma. The impact of various concentrations of antibodies to Infliximab on the quantification of biosimilars was also tested.ResultsA good correlation of SB2, CT-P13 and reference Infliximab spiked serum samples was observed with the four assays. The observed bias between the original drug and biosimilars is clinically insignificant and less than the usual analytical variability observed with these methods. The quantification of the biosimilars and Infliximab was equally impacted in serums containing antibodies to Infliximab. The recovery of the drugs was inversely correlated with the concentration of anti-Infliximab antibodies, suggesting common immunodominant epitopes for SB2, CT-P13 and Infliximab.ConclusionThe ability of these assays to properly quantify the biosimilars Renflexis® and Inflectra® has been demonstrated. The therapeutic drug monitoring required for Infliximab therapy can be adequately performed with the biosimilars using the kits currently in use or available in clinical laboratories.     

Effectiveness of Switching From Intravenous to Subcutaneous Infliximab in Patients With Inflammatory Bowel Diseases: the REMSWITCH Study

Background and AimsWe assessed the effectiveness of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases (IBDs) treated with or without intensified intravenous regimen.MethodsIn this multicenter observational study, IBD patients in clinical remission (partial Mayo score ≤2 or Harvey-Bradshaw index ≤4) were switched to a unique dose of subcutaneous infliximab (120 mg every other week). Pharmacological and biological data were collected at baseline, visit 1 (4–8 weeks postswitch), visit 2 (8–16 weeks postswitch), and visit 3 (16–24 weeks postswitch). Relapse was defined as clinical relapse or fecal calprotectin increase ≥150 μg/g compared with baseline.ResultsAmong 184 eligible patients, 72.3% (n = 133 of 184) agreed to switch to subcutaneous infliximab. At visit 3, a relapse occurred in 10.2% (n = 6 of 59), 7.3% (n = 3 of 38), 16.7% (n = 3 of 18), and 66.7% (n = 10 of 15) (P < .001) of patients receiving 5 mg/kg every 8 weeks, 10 mg/kg every 8 weeks, 10 mg/kg every 6 weeks, and 10 mg/kg every 4 weeks, respectively. Dose escalation to 240 mg every other week led to recapture clinical remission in 93.3% (n = 14 of 15). Infliximab serum levels increased after the switch (P < .0001) except for patients receiving 10 mg/kg every 4 weeks. In multivariable analysis, 10 mg/kg every 4 weeks regimen (odds ratio, 12.4; 95% confidence interval, 1.6–98.4; P = .017) and fecal calprotectin >250 μg/g at baseline (odds ratio, 5.4; 95% confidence interval, 1.1–27.6; P = .042) had a higher risk of relapse as well as reduced (41.7%) or stable (36.8%) infliximab serum levels between baseline and visit 1 compared with increased serum levels (12.7%) (P = .020 and P = .019, respectively). Patients’ acceptability (10-point scale) was improved by the switch (6.9 ± 1.6 vs 8.6 ± 1.4; P < .0001). No severe adverse event was reported.ConclusionsSwitching from intravenous to subcutaneous infliximab 120 mg every other week is safe and well accepted, leading to a low risk of relapse in IBD patients except for those receiving 10 mg/kg every 4 weeks requiring 240 mg every other week.