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Licensed Unlicensed Requires Authentication Published by De Gruyter August 24, 2022

Therapeutic drug monitoring of teriflunomide: do plasma concentrations predict response to leflunomide in patients with rheumatoid arthritis?

  • Tekaya Rawdha , Ben Tekaya Aicha EMAIL logo , Ben Ammar Lobna , Salouaje Issam , Ben Sassi Mouna , Saidane Olfa , Bouden Selma , Ben Brahim Takoua , Ben Abdelghani Kawther , Metoui Leila , Sahli Hana , Mahmoud Ines and Abdelmoula Leila

Abstract

Objectives

Leflunomide is a commonly used treatment for rheumatoid arthritis. It acts by inhibiting dihydroorotate dehydrogenase through its active metabolite teriflunomide. The objective of the study was to investigate the relation between plasma-concentration of teriflunomide and disease-activity in rheumatoid arthritis.

Methods

Data were collected from patients with rheumatoid arthritis on a stable leflunomide dose for at least 2 months. Socio-demographic data, disease characteristics and DAS28 score were recorded. Blood samples were taken for determination of teriflunomide concentration.

Results

A total of 32 serum concentration-time measurements were collected. The concentration of teriflunomide was positively correlated with disease duration of RA (r2=0.2264) and the number of swollen joints (r2=0.2413). There was a trend towards a positive correlation between Health Assessment Questionnaire (HAQ) and plasma teriflunomide concentration (r2=0.1699). Weight was negatively correlated with the residual plasma concentration of teriflunomide (r2=0.2483). However, there was no significant correlation between residual-plasma-concentration of teriflunomide and the following parameters: age, sex, number of tender painful joints, patient-global-assessment, C-reactive protein (CRP) and duration of prescription of leflunomide. We did not find association between disease-activity and residual-plasma-concentration of teriflunomide (r2=0.0021) and haven’t been able to define the threshold value of residual-plasma-concentration of leflunomide predictive of a good-response.

Conclusions

We did not find a concentration-effect-relationship. However, therapeutic drug monitoring of teriflunomide may be useful to ensure adherence and evaluate toxic-levels in case of adverse-events.


Corresponding author: Ben Tekaya Aicha, Rheumatology Department, Charles Nicolle Hospital, Tunis, Tunisia; and Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study was approved by the local Ethics Committee of Charles Nicolle Hospital.

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Received: 2022-01-07
Accepted: 2022-06-01
Published Online: 2022-08-24

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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