Periodic Reporting for period 1 - SQUEEZE (Maximising Impact of Prescription Drugs in Rheumatoid Arthritis)
Okres sprawozdawczy: 2022-12-01 do 2024-05-31
There is a significant need for better selection of treatments for patients with rheumatoid arthritis (RA). Current treatment options, particularly the first line therapy methotrexate, are often not very effective in helping the patients achieve a symptom-free state (remission). We need improved methods to determine which patients will respond to specific medications, as current approaches aren’t personalized enough as well as better tools, like biomarkers, to help tailor treatments to individual needs. In addition, shared-decision making processes should be advanced in routine clinical care to guarantee satisfaction with disease management and thereby increasing adherence of patients to medication.
The SQUEEZE project is focused on using advanced indicators to make treatment of RA more personalized, effective, and safe for patients. It seeks to personalize medication choices, ensuring that patients receive the most effective drugs for their condition. Additionally, the program aims to enhance the safety and efficacy of treatments by monitoring key indicators for better medication management. Finally, SQUEEZE plans to create collaborative care models that involve patients and healthcare providers in decision-making and will collaborate with other initiatives to improve the overall RA treatment landscape.
The SQUEEZE project is focused on using advanced indicators to make treatment of RA more personalized, effective, and safe for patients. It seeks to personalize medication choices, ensuring that patients receive the most effective drugs for their condition. Additionally, the program aims to enhance the safety and efficacy of treatments by monitoring key indicators for better medication management. Finally, SQUEEZE plans to create collaborative care models that involve patients and healthcare providers in decision-making and will collaborate with other initiatives to improve the overall RA treatment landscape.
In the first 18 months of the SQUEEZE project, several significant achievements were made across various work packages.
For example, the consortium has set the stage for performing large scale analysis of existing clinical datasets from patients with RA. A first data extraction including harmonization was performed focusing on patients who started their first line therapy. Analysis of extracted data on treatment responses and disease activity was performed. This included the assessment of methotrexate (MTX) dosing patterns and their association with clinical remission rates, which were analyzed using logistic regression models.
The ongoing efforts in the SQUEEZE project aim to create a reference dataset of Torque-Teno-Virus (TTV) levels in DMARD-treated RA patients, which will help in further understanding the relationship between TTV levels and treatment responses. This includes the collection and analysis of clinical data linked to biosamples (serum or plasma) for establishing a comprehensive dataset.
In addition, all clinical and observational trials within the SQUEEZE project have received approval by regulators/ethical committees to start recruiting patients which will allow the timely conduction of the studies.
Methodologies for measuring drug levels and adherence were optimized and validated, particularly for MTX and its metabolites. This will enhance the interpretability of trial results and help distinguish between non-responders and non-adherent patients.
The project has made significant achievements in therapeutic drug monitoring (TDM) in patients treated with Adalimumab, a biological DMARD by developing algorithms to adjust drug doses based on assessed drug levels and anti-drug antibodies.
Furthermore, a systematic literature review was conducted, screening over 12,000 records and ultimately including 123 studies. This review analyzed safety outcomes of currently licensed biologic and targeted synthetic DMARDs and will contribute to a better understanding of their effectiveness and safety profiles.
Finally, we conducted a so-called “contextual analysis” to understand current treatment practices, contextual factors in RA care and influencing behaviors that are or will be critical for the development, implementation, and evaluation of the results of SQUEEZE.
These achievements reflect a strong foundation for the ongoing work of the SQUEEZE project and set the stage for further advancements in understanding and optimizing treatment for RA.
For example, the consortium has set the stage for performing large scale analysis of existing clinical datasets from patients with RA. A first data extraction including harmonization was performed focusing on patients who started their first line therapy. Analysis of extracted data on treatment responses and disease activity was performed. This included the assessment of methotrexate (MTX) dosing patterns and their association with clinical remission rates, which were analyzed using logistic regression models.
The ongoing efforts in the SQUEEZE project aim to create a reference dataset of Torque-Teno-Virus (TTV) levels in DMARD-treated RA patients, which will help in further understanding the relationship between TTV levels and treatment responses. This includes the collection and analysis of clinical data linked to biosamples (serum or plasma) for establishing a comprehensive dataset.
In addition, all clinical and observational trials within the SQUEEZE project have received approval by regulators/ethical committees to start recruiting patients which will allow the timely conduction of the studies.
Methodologies for measuring drug levels and adherence were optimized and validated, particularly for MTX and its metabolites. This will enhance the interpretability of trial results and help distinguish between non-responders and non-adherent patients.
The project has made significant achievements in therapeutic drug monitoring (TDM) in patients treated with Adalimumab, a biological DMARD by developing algorithms to adjust drug doses based on assessed drug levels and anti-drug antibodies.
Furthermore, a systematic literature review was conducted, screening over 12,000 records and ultimately including 123 studies. This review analyzed safety outcomes of currently licensed biologic and targeted synthetic DMARDs and will contribute to a better understanding of their effectiveness and safety profiles.
Finally, we conducted a so-called “contextual analysis” to understand current treatment practices, contextual factors in RA care and influencing behaviors that are or will be critical for the development, implementation, and evaluation of the results of SQUEEZE.
These achievements reflect a strong foundation for the ongoing work of the SQUEEZE project and set the stage for further advancements in understanding and optimizing treatment for RA.
The current results of the SQUEEZE project indicate significant progress for the research on RA treatment by identifying and compiling a list of defined research questions aimed at identifying treatment-responsive patients, along with the necessary data for these inquiries.
The project has already increased our understanding of MTX dosing patterns among patients by revealing distinct patients subgroups based on their treatment regimens. For instance, patients in different clusters exhibit varying patterns of MTX initiation and dosage adjustments over time, which is crucial for further predictive analyses related to treatment effectiveness.
Additionally, the project has engaged in collaborations with pharmaceutical companies to gather data on serum drug levels and their clinical effects, particularly for subcutaneous TNF inhibitors. This collaboration has facilitated the identification of therapeutic ranges for these drugs, which is essential for optimizing treatment strategies.
Furthermore, two new methodologies have been developed to measure adherence to MTX within clinical trials: 1) sweat analysis and 2) blood analysis of active MTX.
Then, through dilution experiments, we established the minimum amount of biosample for TTV analysis. This is an essential first step towards using TTV as a new biomarker for RA patients.
Finally, the achievements of the contextual analysis contribute significantly to understanding the ways in which the SQUEEZE eHealth facilitated integrated care model operates on a Swiss and an EU level, ultimately aiming to enhance medication adherence and improve treatment outcomes for patients.
The project has already increased our understanding of MTX dosing patterns among patients by revealing distinct patients subgroups based on their treatment regimens. For instance, patients in different clusters exhibit varying patterns of MTX initiation and dosage adjustments over time, which is crucial for further predictive analyses related to treatment effectiveness.
Additionally, the project has engaged in collaborations with pharmaceutical companies to gather data on serum drug levels and their clinical effects, particularly for subcutaneous TNF inhibitors. This collaboration has facilitated the identification of therapeutic ranges for these drugs, which is essential for optimizing treatment strategies.
Furthermore, two new methodologies have been developed to measure adherence to MTX within clinical trials: 1) sweat analysis and 2) blood analysis of active MTX.
Then, through dilution experiments, we established the minimum amount of biosample for TTV analysis. This is an essential first step towards using TTV as a new biomarker for RA patients.
Finally, the achievements of the contextual analysis contribute significantly to understanding the ways in which the SQUEEZE eHealth facilitated integrated care model operates on a Swiss and an EU level, ultimately aiming to enhance medication adherence and improve treatment outcomes for patients.