About

Squeezing the most out of existing drugs

About

Squeezing the most out of existing drugs

Background

Rheumatoid arthritis (RA) is a chronic immune-mediated disease affecting approximately 5 million EU citizens, with enormous impact on their quality of life and on social and health systems; just think that approximately 1 out of 3 patients will drop off work five years after diagnosis, if not properly treated.
Many disease modifying antirheumatic drugs (DMARDs) are currently available to treat people with RA; however, many will fail or cause side effects until the best therapy for that individual patients is identified. Why can’t rheumatologists choose the best treatment right away? Unfortunately, available markers are insufficient to guide the decision (true precision medicine), and so, for a third of patients with RA, treatment strategies are still ineffective, cumbersome, and expensive.
Our team of leading academic centres with a first-class record in translational and clinical research, together with patient research partners and small and medium-sized enterprises (SMEs), has set out to deliver a collaborative programme to advance the clinical application of biomarkers to improve benefit, safety, and value of approved DMARDs. SQUEEZE utilizes models from data science, clinical trials, translational, and behavioural science to define the best use of biomarkers and medicines. SQUEEZE results will improve rheumatologists’ ability to select the DMARD with the highest likelihood to fit the patient’s immune and clinical profile, optimise the dose and route of existing DMARDs, and help design an innovative model of care focusing on the patient´s preferences and needs to increase adherence to prescribed medications and satisfaction with treatment.

Our Objectives

SQUEEZE has adopted the following objectives:

  • To identify and validate clinical, laboratory, molecular, and behavioural and psychosocial digital biomarkers to enable the recognition of patients with high likelihood of response to treatment;

  • To identify and validate clinical, laboratory, molecular, and behavioural and psychosocial digital biomarkers to enable the selection of the existing drug with highest chance of benefit for an individual patient;

  • To improve efficacy and safety of existing therapies by validating monitoring biomarkers;

  • To create synergies with other projects, related EU-wide initiatives and other infrastructure.

Our Methodology

The overall conceptual approach of SQUEEZE is underpinned by a complementary methodological approach utilising large-scale data analysis and prospective studies (“clinical trials”) to predict patients likely to respond to drugs, using translational studies and technologies to validate innovative biomarker platforms, and embracing behavioural studies including design thinking to fuel real-life translation (“implementation science”). Thematically, the work streams address the identified unmet needs in essentially three areas of clinical relevance: (a) lack of guidance on choosing the right drug; (b) insufficient dose or route while on a specific drug; and (c) lack of a care setting and digital support tools that are permissive to full exploitation of drug benefits through shared decision making and adherence in the long run of a patient’s journey.

SQUEEZE will use three clinical trials to address several of its objectives:

  1. The SQUEEZE prospective biomarker trial (The BioTest Trial, coordinated by QMUL, London) aims to confirm the relationship between target expression levels in the disease tissue (synovial tissue) and the treatment response for targeted modes of action (MOA) DMARDs;
  2. The methotrexate dose/route optimisation trial (The MethMax Trial, coordinated by MUW, Vienna), aims to optimize the MTX dose and route;
  3. The therapeutic drug monitoring (TDM) trial (The RA-DRUM Trial coordinated by DS, Oslo), aims to determine if with dose adjustment according to serum drug levels and anti-drug antibodies improves effectiveness during maintenance therapy with TNF inhibitors.

Refers to “the scientific study of methods to promote the systematic uptake of research findings and other evidence-based practices into routine practice and, hence, to improve the quality and effectiveness of health services and care”. This will be reached through:

  • Stakeholder involvement
  • Contextual analysis using a multi-methods approach
  • Co-creation and pilot testing with end users of the SQUEEZE eHealth facilitated integrated care model including digital tools (SCM-DTx).

Impact

  • At SQUEEZE, our scientific focus is on uncovering and confirming critical biomarkers, spanning clinical, laboratory, molecular, behavioural, and psychosocial domains. This process enables us to pinpoint patients with a high likelihood of positive treatment responses, ultimately reducing the duration of patient suffering.

  • Beyond traditional markers, we delve into digital biomarkers, examining behavioural patterns and psychosocial elements. This comprehensive approach allows us to fine-tune treatment selection, optimizing benefits for individual patients and decrease costs for individuals and society at large.​

  • Moreover, our commitment extends to validating monitoring biomarkers, enhancing the effectiveness and safety of current therapies. This not only fortifies the trust within the patient-doctor relationship but also contributes to the overall satisfaction and well-being of the healthcare team. ​