Introduction Therapeutic drug monitoring (TDM) in inflammatory rheumatic diseases (RMDs) is gaining interest. However, there are unresolved questions about the best practices for implementing TDM effectively in clinical settings. Objective The primary objective of this study was to evaluate whether early TDM of adalimumab predicts drug survival at 52 weeks in patients with RMDs. The secondary objective was to identify factors associated with pharmacokinetic failure and treatment discontinuation. Methods A retrospective cohort study included patients aged ≥ 18 years with RMDs who initiated adalimumab therapy. Early TDM was performed within the first 26 weeks, and adalimumab trough levels (ATL) and anti-drug antibodies were measured. Drug survival was assessed at 52 weeks and defined as the time from adalimumab initiation to discontinuation for any reason. Multivariate analyses were conducted to identify factors influencing outcomes. Results The study included 194 patients, of whom 56.7% exhibited ATL below the therapeutic range during the first 26 weeks. In the multivariate analysis, subtherapeutic concentrations were significantly associated with higher weight (OR = 1.02; p = 0.040) and ankylosing spondylitis diagnosis (OR = 3.68; p < 0.001). At 52 weeks, 43.8% of patients had discontinued adalimumab. Low ATL (< 1 µg/mL) was strongly associated with treatment discontinuation (OR = 7.31; p < 0.001), while concomitant methotrexate reduced this risk (OR = 0.46; p = 0.026). Conclusions Early TDM of adalimumab predicts drug persistence and underscores its clinical relevance as a proactive tool to guide personalized treatment and reduce the risk of treatment failure. These findings highlight the importance of incorporating TDM into routine practice to optimize therapeutic outcomes.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> Key Points • Early TDM of adalimumab in rheumatic diseases shows that low drug exposure predicts reduced drug survival at 52 weeks. • Approximately half of the patients exhibit low adalimumab exposure with the standard dose (40 mg every other week). • Body weight and methotrexate use significantly impact adalimumab levels. • Immunogenicity, found in 14.4% of patients with low ADL levels, underscores the need for early ADA detection to prevent non-response and discontinuation. </entry> </row> </tbody> </tgroup> </Table>

Assessing early therapeutic drug monitoring of adalimumab as a predictor of treatment efficacy and immunogenicity in rheumatic diseases: “early therapeutic drug monitoring of adalimumab”

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2025年1月18日

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Patricia Ortiz-Fernández,
Carles Iniesta-Navalón,
Elena Urbieta-Sanz,
Juan José Gascón-Cánovas

摘要

Introduction

Therapeutic drug monitoring (TDM) in inflammatory rheumatic diseases (RMDs) is gaining interest. However, there are unresolved questions about the best practices for implementing TDM effectively in clinical settings.

Objective

The primary objective of this study was to evaluate whether early TDM of adalimumab predicts drug survival at 52 weeks in patients with RMDs. The secondary objective was to identify factors associated with pharmacokinetic failure and treatment discontinuation.

Methods

A retrospective cohort study included patients aged ≥ 18 years with RMDs who initiated adalimumab therapy. Early TDM was performed within the first 26 weeks, and adalimumab trough levels (ATL) and anti-drug antibodies were measured. Drug survival was assessed at 52 weeks and defined as the time from adalimumab initiation to discontinuation for any reason. Multivariate analyses were conducted to identify factors influencing outcomes.

Results

The study included 194 patients, of whom 56.7% exhibited ATL below the therapeutic range during the first 26 weeks. In the multivariate analysis, subtherapeutic concentrations were significantly associated with higher weight (OR = 1.02; p = 0.040) and ankylosing spondylitis diagnosis (OR = 3.68; p < 0.001). At 52 weeks, 43.8% of patients had discontinued adalimumab. Low ATL (< 1 µg/mL) was strongly associated with treatment discontinuation (OR = 7.31; p < 0.001), while concomitant methotrexate reduced this risk (OR = 0.46; p = 0.026).

Conclusions

Early TDM of adalimumab predicts drug persistence and underscores its clinical relevance as a proactive tool to guide personalized treatment and reduce the risk of treatment failure. These findings highlight the importance of incorporating TDM into routine practice to optimize therapeutic outcomes.

Key Points

• Early TDM of adalimumab in rheumatic diseases shows that low drug exposure predicts reduced drug survival at 52 weeks.

• Approximately half of the patients exhibit low adalimumab exposure with the standard dose (40 mg every other week).

• Body weight and methotrexate use significantly impact adalimumab levels.

• Immunogenicity, found in 14.4% of patients with low ADL levels, underscores the need for early ADA detection to prevent non-response and discontinuation.