Subcutaneous injection of infliximab CT‐P13 results in stable drug levels within 14‐day treatment cycle in Crohn’s disease

Abstract

Summary The new subcutaneous (sc) formulation of the infliximab (IFX) biosimilar CT‐P13 results in homogeneous serum trough concentrations of IFX at steady state. The present study aimed to investigate in Crohn’s disease (CD) patients the intra‐individual variations of IFX drug levels at multiple time‐points during 2 consecutive cycles of maintenance therapy with CT‐P13 sc. Patients and Methods CD patients in clinico‐biological remission under maintenance therapy with intravenous (iv) IFX/CT‐P13 were switched to CT‐P13 sc 8 weeks (W) after the last infusion. They were treated with CT‐P13 sc, 120 mg every 2 W. Assessments were performed from 8 W after starting CT‐P13 sc and patients had to attend 6 visits on 2 consecutive cycles of treatment (cycles A and B). Visits were scheduled on days 4–6 (visit 1), days 7–9 (visit 2) and day 14 (visit 3) of each cycle, where days 1 and 14 were the days of sc injection of CT‐P13. At each visit, peripheral blood was collected to measure serum IFX levels and anti‐drug antibodies. Results Twenty patients underwent 120 evaluations. Large intra‐individual variations of serum drug levels of IFX were observed. When pooling the 120 evaluations, the mean drug level was 11.3 ± 4.9 μg/ml, and the median drug level was 10.9 μg/ml (IQR 7.5–15.5). During each cycle, the median drug levels were similar between visits 1 and 2 as well as between visits 1 and 3 and between visits 2 and 3. In cycle A, median drug levels were 11.1 μg/ml (7.8–14.5), 12.0 μg/ml (7.2–16.1) and 11.0 μg/ml (7.5–15.1) at V1, V2 and V3, respectively. Similar results were obtained in cycle B, where median drug levels were 11.6 μg/ml (7.9–14.9), 11.4 μg/ml (8.1–15.2) and 10.9 μg/ml (7.9–15.6) at V1, V2 and V3, respectively. In univariate analysis, we failed to identify factors predictive of low drug levels. Conclusions IFX drug levels are quite stable within 14‐day treatment cycle, without trough levels in CD patients in remission during the maintenance therapy with CT‐P13 sc. In patients with inactive CD under maintenance therapy with CT‐P13 sc, therapeutic drug monitoring of IFX can be performed at any time between two CT‐P13 sc injections.

Editorial: is there a role for monitoring intermediate anti‐TNF drug concentrations in IBD?

“…Although limited by the rather small sample size and the short duration of follow-up, this study demonstrated that CT-P13 concentrations are quite stable within the two-week treatment cycle in patients with inactive CD implying that TDM could be performed at any time between sc injections. 4 The findings from this study are in-line with the prospective POETIC (Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations) study showing that intermediate adalimumab concentrations did not differ from trough concentrations in 29 patients with CD. 5 The POETIC study used a drug-tolerant assay also showed that anti-drug antibody (ADA) levels were similarly measured either at trough or inbetween injections.…”

“…5 The POETIC study used a drug-tolerant assay also showed that anti-drug antibody (ADA) levels were similarly measured either at trough or inbetween injections. 5 Assessment of ADA could not be investigated in the study by Roblin and colleagues 4 as a drug-sensitive assay was used and none of the patients had undetectable drug concentrations. Another prospective study found that adalimumab concentrations remained stable only for the first 9 days of the drug cycle before declining to trough.…”

“…A novel prospective study by Roblin and colleagues 4 aimed to evaluate drug concentrations over two dosing cycles at different time points in 20 patients with Crohn’s disease (CD) in clinical and biologic remission receiving maintenance sc therapy with 120 mg CT‐P13 (an infliximab biosimilar) every 2 weeks for 8 weeks. Although limited by the rather small sample size and the short duration of follow‐up, this study demonstrated that CT‐P13 concentrations are quite stable within the two‐week treatment cycle in patients with inactive CD implying that TDM could be performed at any time between sc injections 4 …”

Editorial: is there a role for monitoring intermediate anti‐TNF drug concentrations in IBD? Authors’ reply

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We read with great interest the editorial by Profs Rakowsky, Papamichael and Cheifetz in response to our recently published study on therapeutic drug monitoring (TDM) of subcutaneous CT-P13. 1,2 We agree with the vast majority of the comments made. 3 Indeed, our study is a first step in demonstrating whether TDM is useful in monitoring subcutaneous biotherapies.

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

“…In our patients, drug levels were determined within 24 h prior to the following SC CT-P13 injection or immediately before this dose. However, it has been described that drug levels would remain stable throughout the 14 days of the treatment cycle, so the determination would not be subject to trough levels as occurs with intravenous dosing [ 19 ].…”