Potential application of measuring serum infliximab levels in rheumatoid arthritis management: A retrospective study based on KURAMA cohort data

Abstract

Infliximab (IFX) therapy has considerably improved the treatment of rheumatoid arthritis (RA). However, some patients still do not respond adequately to IFX therapy, or the efficacy of the treatment diminishes over time. Although previous studies have reported a relationship between serum IFX levels and therapeutic efficacy, the potential applications of IFX therapeutic drug monitoring (TDM) in clinical practice remain unclear. The purpose of this study was to investigate the potential applications of IFX TDM by analyzing a Japanese cohort database. Data were collected retrospectively from the Kyoto University Rheumatoid Arthritis Management Alliance cohort between January 1, 2011, and December 31, 2018. Serum IFX levels were measured using a liquid chromatography-tandem mass spectrometer. Out of the 311 RA patients that used IFX, 41 were eligible for the analysis. Serum IFX levels were significantly higher in responders than in non-responders. An optimal cut-off value was determined to be 0.32 μg/mL based on a receiver operating characteristic curve. At the IFX measurement point, a better therapeutic response was observed in the high IFX group (n = 32) than in the low IFX group (n = 9). Conversely, at the maximum effect point, when DAS28-ESR was the lowest between IFX introduction and measurement points, there were no differences in responder proportions between the low and high IFX groups. IFX primary ineffectiveness could be avoided with appropriate dose escalation without blood concentration measurement in clinical practice. In conclusion, IFX TDM could facilitate the identification of secondary non-responders and in turn, proper IFX use.

Association of Serum Dupilumab Levels at 16 Weeks With Treatment Response and Adverse Effects in Patients With Atopic Dermatitis

“…Interestingly, the present study suggests that observed serum dupilumab levels were not related to treatment response. This is in contrast to certain monoclonal antibodies used in other diseases (ie, TNF-inhibitor in other autoimmune diseases) . It may be that response is dependent on target availability of the IL-4Rα, with an interpatient variability producing heterogeneity in response.…”

“…This is in contrast to certain monoclonal antibodies used in other diseases (ie, TNF-inhibitor in other autoimmune diseases). 6,[11][12][13] It may be that response is dependent on target availability of the IL-4Rα, with an interpatient variability producing heterogeneity in response. However, because serum dupilumab levels are relatively high, the IL-4Rα in all patients was likely fully saturated at week 16.…”

A rapid and universal liquid chromatograph-mass spectrometry-based platform, refmAb-Q nSMOL, for monitoring monoclonal antibody therapeutics

“…We have applied and validated the nSMOL assay for more than 40 mAbs including 2 Fc fusion proteins. 8,9,21,47–49 The exquisite specificity of mAbs and availability of 6 CDR legions (3 from each heavy and light chains) enables robust selection of the signature peptide as we and others have demonstrated. 31 Therefore, we do not anticipate encountering difficulties in identifying a signature peptide as we expand our portfolio for the nSMOL method into the rest of FDA- and EMA-approved mAbs.…”

“…Major advantages of the refmAb-Q nSMOL assay stem from its backbone, the nSMOL assay. We have applied and validated the nSMOL assay for more than 40 mAbs including 2 Fc fusion proteins 8,9,21,[47][48][49] . The exquisite specificity of mAbs and availability of 6 CDR legions (3 from each heavy and light chains)…”

A rapid and universal liquid chromatograph-mass spectrometry-based platform, refmAb-Q nSMOL, for monitoring monoclonal antibody therapeutics

“…Major advantages of the refmAb-Q nSMOL assay stem from its backbone, the nSMOL assay. We have applied and validated the nSMOL assay for more than 40 mAbs including 2 Fc fusion proteins 8,9,21,46-48 . The exquisite specificity of mAbs and availability of 6 CDR legions (3 from each heavy and light chains) enables robust selection of the signature peptide as we and others have demonstrated 30 .…”