AB1675-PARE EXPLORING THE RELATIONSHIP BETWEEN ADALIMUMAB THROUGH LEVELS AND FIVE PATIENT REPORTED OUTCOME MEASURES IN RHEUMATOID ARTHRITIS THE LADDER STUDY (2024)

Abstract

Background: Adalimumab, a biologic DMARD, plays a central role in the management of rheumatoid arthritis (RA). Though highly effective for many patients, the response varies significantly among others, emphasizing the need for personalized treatment. A potential tool to tackle this challenge is therapeutic drug monitoring (TDM). TDM involves optimizing dosages based on serum drug concentrations. In current practice, the efficacy of RA treatment is assessed through the Disease Activity Score (DAS), an objective, validated and standardised clinical outcome measure. However, alongside DAS, Patient-Reported Outcome Measures (PROMs) have increasingly become indispensable in the management of RA as they provide a subjective assessment of the health status of a patient^[1]. The RAID, FACIT-F, HAQ-DI, EQ-5Dvas and EQ-5Dindex are health-related questionnaires used to assess respectively the impact of the disease, fatigue, functional disability, self-related health and health-related quality of life and allow for specifying the exact domain in which the patient is experiencing disease worsening. Thus, in contrast to the DAS, PROMs are full subjective questionnaires, completed by patients, offering invaluable insights into their perceived treatment efficacy. Integrating TDM and PROMs in the management of RA ultimately contributes to optimization of RA treatment by ensuring adequate drug exposure while focusing on patient-relevant outcomes.

Objectives: This study aims to assess the correlation between adalimumab trough levels with the RAID, FACIT-F, HAQ-DI, EQ-5Dvas and EQ-5Dindex to assess optimal therapy of adalimumab in RA patients.

Methods: RA patients treated with adalimumab were included if they completed a minimum of one PROM within a 6 month time-frame surrounding adalimumab blood sampling. Blood samples were assumed therapeutic between 5 and 8 μg/ml. The RAID, FACIT-F, HAQ-DI, EQ-5Dvas and EQ-5Dindex were employed to assess the impact of disease, fatigue, functional disability, self-rated health, and health-related quality of life, respectively. In addition, DAS28CRP was measured. Findings were tested for statistical significance using regression analysis. To assess clinical relevance, cut-off values and Minimal Clinically Important Differences (MCIDs) were used.

Results: A total of 51 patients, representative of a typical RA population, were enrolled. Analysis using cut-off values indicated that patients with therapeutic trough levels of adalimumab more frequently achieved remission or low disease activity across all five PROMs, compared to those with non-therapeutic trough levels. Additionally, MCIDs revealed clinically relevant differences in outcomes for the FACIT-F, HAQ-DI and EQ-5Dindex. Notably, women exhibited significantly higher scores in FACIT-F and HAQ-DI, suggesting a greater experience of fatigue and functional disability compared to men. Moreover, a significant correlation was seen between DAS28CRP and the RAID, HAQ-DI, EQ-5Dvas, and EQ-5Dindex, affirming the validity of these four RA-related PROMs in relation to the DAS. However, statistical analysis did not show a significant association between adalimumab exposure and the five measured PROMs. It is crucial to recognize that clinical relevance often surpasses statistical significance. The absence of statistical significance in our study may stem from the limited sample size.

Conclusion: This prospective observational study, reflecting real-life clinical practice, shows that therapeutic adalimumab trough levels are associated with a clinically relevant improvement in domains fatigue, functional disability and health-related quality of life. In addition, this study emphasizes the importance of considering gender differences in RA treatment with adalimumab. To strengthen our findings and underscore the significance of PROMs in RA patient care, further research with larger sample sizes are needed.

REFERENCES: [1] Furst, D. E., et al. Final 10-year effectiveness and safety results from study DE020: adalimumab treatment in patients with rheumatoid arthritis and an inadequate response to standard therapy. Rheumatology 2015; 54(12): 2188-2197.

Acknowledgements: Thanks to all the patients who participated in this study.

Disclosure of Interests: None declared.