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 health-related quality of life and socioeconomic impact; as evidenced for example by approximately one third of patients dropping out of the work process five years after diagnosis (http://www.eumusc.net). The impact of RA on patients, health care providers, and regulators is therefore extraordinary. A broad choice of disease modifying antirheumatic drugs (DMARDs) with different targets is up to date available in clinical care, however without sufficient markers indicating the best choice for a particular patient, treatment strategies can be ineffective, cumbersome and expensive.

Our team of leading academic centres with a first-class record in translational and clinical research, together with patients 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 science, and behavioural science to engage in a complementary, synergistic, and non-overlapping manner addressing the use of biomarkers to improve the ability to select the DMARD with the highest likelihood of fitting the immunophenotypic and clinical profile of the patient, to optimise dose and route of existing DMARDs; and to inform an innovative model of care focusing on patient´s preferences and needs to increase adherence to prescribed drugs.

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.

THE CLINICAL TRIALS

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 infliximab.

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).