Antibodies to infliximab in Remicade-treated rheumatic patients show identical reactivity towards biosimilars

2016 ◽  
Vol 75 (9) ◽  
pp. 1693-1696 ◽  
Author(s):  
M Begoña Ruiz-Argüello ◽  
Ainara Maguregui ◽  
Ainhoa Ruiz del Agua ◽  
Dora Pascual-Salcedo ◽  
Ana Martínez-Feito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
Therapeutic Drug Monitoring ◽  
Rheumatic Diseases ◽  
Drug Monitoring ◽  
Correlation Coefficients ◽  
Therapeutic Drug ◽  
Switching Strategy ◽  
Loss Of Response ◽  
Rheumatic Patients

ObjectivesThe aim of this study was to determine whether antibodies to infliximab (IFX) in Remicade-treated patients cross-react with the biosimilar CT-P13.Methods250 consecutive patients with rheumatic diseases under Remicade and 77 controls were retrospectively selected for the study. Anti-IFX antibodies at drug through levels were measured in parallel with three different bridging ELISA assays: Promonitor-ANTI-IFX kit, which uses Remicade to detect antibodies, and two more assays that use either Inflectra or Remsima with the same format. Correlation and association between each assay was studied.Results50.4% of patients were tested positive with Promonitor-ANTI-IFX. All were antibodies to IFX (ATI)-positive when either Inflectra or Remsima assays were used. In all comparisons positive and negative percentage agreements were 100%, and correlation coefficients were ≥0.995. No differences between rheumatoid arthritis and spondyloarthritis, or between concomitant immunosuppressives, were observed.ConclusionsAnti-IFX antibodies of Remicade-treated patients cross-react with either Inflectra or Remsima. Although additional epitopes may be present in the biosimilar, results suggest that epitopes influencing the immune response to IFX are also present in the biosimilar. Antibody-positive patients treated with Remicade should not be switched to the biosimilar, since antibodies will interact with the new drug and potentially lead to loss of response. This finding supports the utility for therapeutic drug monitoring before a switching strategy is considered.

scholarly journals P346 Single-centre experience of ustekinumab: Therapeutic drug monitoring in Crohn’s disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S331-S333
Author(s):  
C Liefferinckx ◽  
M Fassin ◽  
D Thomas ◽  
C Minsart ◽  
A Cremer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Crohn's Disease ◽  
Median Time ◽  
Real World ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Loss Of Response

Abstract Background Therapeutic drug monitoring (TDM) is a diagnostic tool in the monitoring of anti-TNF therapies. Yet, the benefit for TDM of new biologics such as ustekinumab (USK) is still controversial in real-world experiences. Methods This monocentric retrospective study aims to correlate USK trough levels (TLs) with clinical and endoscopic data. All patients have given written consent to the Biobank (B2011/005). Endoscopic disease was defined as quiescent in absence of endoscopic lesions, mild disease in presence of few superficial ulcerations, moderate in presence of several ulcers and severe in presence of numerous deep ulcers and/or inflammatory stenosis. 313 serum USK samples from 67 Crohn’s disease patients were used to measure USK TL (USK ELISA, apDia) while 88 samples (at week 16, and before and after optimisation) were used to measure anti-drug antibody (ADA), using a drug-tolerant affinity capture elution anti-ustekinumab assay Results Demographic and baseline data of our population are presented in Table 1. The median follow-up was 73 weeks (IQR 39–92). An optimisation due to loss of response was required in 44.8% of patients (n = 30) after a median time of 38 weeks (IQR 24–55). To evaluate the drug efficacy, an endoscopy was performed in 61% of cases at a median time of 35 weeks (IQR 27–47). TLs were 5.2 µg/ml (IQR 2.1–8.8), 1.7 µg/ml (IQR 0.3–4.3) and 2.6 µg/ml (IQR 0.6–4.1) at week 8, 16 and 24, respectively. TLs at week 8 were correlated to the induction IV dose administrated (r = 0.3, p = 0.03). At week 16, low TLs were associated with higher endoscopic activity in the follow-up (p = 0.02), although this was not the case at week 8 (p = 0.5) (Figure 1). Patients not requiring an optimisation had higher TLs in maintenance than patients requiring optimisation (2.45 µg/ml (IQR 1.3–4.4) vs. 1.15 µg/ml (IQR 0.1–2.24), p = 0.008). Obviously, optimisation significantly increased TLs (1.15 µg/ml (IQR 0.1–2.24) vs. 6.6 µg/ml (IQR 2.3–11.3), p < 0.001). ADA were undetectable in all the measured samples in maintenance. Conclusion This real-world experience confirms a drug exposure-endoscopic response relationship. Week 16 seems to be an appropriate time point to monitor drug exposure. Earlier USK TLs, at week 8, appear less valuable to be monitored due to the influence of initial IV dose. The absence of immunogenicity suggests that it is not a key driver in the loss of response.

scholarly journals Therapeutic Drug Monitoring Guides the Management of Crohn’s Patients with Secondary Loss of Response to Adalimumab

2018 ◽  
Vol 24 (7) ◽  
pp. 1531-1538 ◽  
Author(s):  
Sophie Restellini ◽  
Che-yung Chao ◽  
Peter L Lakatos ◽  
Achuthan Aruljothy ◽  
Haya Aziz ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Secondary Loss ◽  
Loss Of Response

scholarly journals The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Robert A. Mitchell ◽  
Constantin Shuster ◽  
Neal Shahidi ◽  
Cherry Galorport ◽  
Mari L. DeMarco ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Statistical Significance ◽  
Therapeutic Drug ◽  
Loss Of Response ◽  
Remission Rates ◽  
Inflammatory Bowel ◽  
Group 3

Background. Infliximab (IFX) therapeutic drug monitoring (TDM) allows for objective decision making in patients with inflammatory bowel disease (IBD) and loss of response. Questions remain about whether IFX TDM improves outcomes. Methods. Patients with IBD who had IFX TDM due to concerns for loss of response were considered for inclusion. Serum IFX trough concentration and anti-drug antibody (ADA) concentrations were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX. Changes in management were analyzed according to groupings; remission rates were assessed at 6 months. Results. 71 patients were included of whom 37% underwent an appropriate change in therapy. Groups 1 (67%) and 2 (83%) had high adherence compared to only 9% in group 3. At 6 months, 57% had achieved remission. More patients who underwent an appropriate change in therapy achieved remission, though this did not reach statistical significance (69% versus 49%; P=0.098). Conclusions. A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range.

scholarly journals Combining Therapeutic Drug Monitoring with Biosimilars, a Strategy to Improve the Efficacy of Biologicals for Treating Inflammatory Bowel Diseases at an Affordable Cost

2017 ◽  
Vol 35 (1-2) ◽  
pp. 61-68 ◽  
Author(s):  
Ann Gils
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Drug Efficacy ◽  
European Medicines Agency ◽  
Therapeutic Drug ◽  
Treatment Switching ◽  
Loss Of Response ◽  
Drug Concentrations ◽  
Bowel Diseases

Background: Biologicals provide a tight disease control but not all patients respond favourably to treatment. Some patients do not respond at all (primary non-responders), while other patients respond initially but show loss of response over time (secondary non-responders). Drug concentrations in the serum of patients can be monitored and correlated with biological, clinical or endoscopic response. Therapeutic thresholds have been defined for infliximab and adalimumab. The European Medicines Agency has approved 3 biosimilars of infliximab and new biosimilars are waiting approval. Key Messages: Distinguishing primary non-responders from patients with insufficient drug exposure during induction through drug serum concentration determination will improve drug efficacy. Current algorithms to guide treatment of patients with secondary loss of response take into account that patients with high titers of anti-drug antibodies (ADA) do not respond to dose intensification and that patients with therapeutic drug concentrations cannot be switched to biologicals within class. For patients in clinical remission, the cost of biological treatment can be decreased by dose tapering patients with supra-therapeutic concentrations and/or by switching patients with adequate drug concentrations and no formation of ADA to biosimilar, whereas efficacy can be increased by dose-intensifying patients with low or transient ADA and by switching patients with persistent ADA to biologicals within or out-off class. Conclusions: As an objective tool, therapeutic drug monitoring can identify patients who are eligible for dose tapering, intensification of treatment, cessation of treatment, switching within- or out-of-class and switching to biosimilar.

scholarly journals The performance of Remicade®-optimized quantification assays in the assessment of Flixabi® levels

2018 ◽  
Vol 11 ◽  
pp. 175628481879695 ◽  
Author(s):  
F. Magro ◽  
C. Rocha ◽  
A. I. Vieira ◽  
H. T. Sousa ◽  
I. Rosa ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Intraclass Correlation ◽  
Correlation Coefficients ◽  
Therapeutic Drug ◽  
High Similarity ◽  
Intraclass Correlation Coefficients ◽  
Healthy Donors ◽  
Antidrug Antibodies

Background: The advent of Remicade® biosimilars, Remsima®, Inflectra® and, more recently, Flixabi®, has brought along the potential to decrease the costs associated with this therapy, therefore increasing its access to a larger group of patients. However, and in order to assure a soft transition, one must make sure the assays and algorithms previously developed and optimized for Remicade perform equally well with its biosimilars. This study aimed to: (a) validate the utilization of Remicade-optimized therapeutic drug monitoring assays for the quantification of Flixabi; and (b) determine the existence of Remicade, Remsima and Flixabi cross-immunogenicity. Methods: Healthy donors’ sera spiked with Remicade, Remsima and Flixabi were quantified using three different Remicade-quantification assays, and the reactivity of anti-Remicade and anti-Remsima sera to Remicade and to its biosimilars was assessed. Results: The results show that all tested Remicade-infliximab-optimized assays measure Flixabi as accurately as they measure Remicade and Remsima: the intraclass correlation coefficients between theoretical and measured concentrations varied from 0.920 to 0.990. Moreover, the interassay agreement values for the same compounds were high (intraclass correlation coefficients varied from 0.936 to 0.995). Finally, the anti-Remicade and anti-Remsima sera reacted to the different drugs in a similar fashion. Conclusions: The tested assays can be used to monitor Flixabi levels. Moreover, Remicade, Remsima and Flixabi were shown to have a high cross-immunogenicity, which supports their high similarity but prevents their switching in nonresponders with antidrug antibodies.

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