Ernest Choy: “I expect more patients will achieve remission with combination biologic treatment”

DocTIS is an international research collaboration aiming to revolutionize treatment for six major immune-mediated inflammatory diseases (IMIDs): Crohn’s disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, and psoriatic arthritis. By bringing together leading institutions from Europe and the US, the project seeks to develop more effective, targeted therapies through a systems biology approach.

One of the central contributors to this effort is Cardiff University, which leads the Clinical Study Validation of Combinatorial Therapies work package. This includes key responsibilities such as clinical study design, securing regulatory and ethics approvals, conducting the clinical studies, analysing outcomes, and finalizing reports.

At the helm of Cardiff’s involvement is Dr. Ernest Choy, Professor and Head of Rheumatology. An expert in clinical trial design and evaluation of combinatorial therapies, Dr. Choy brings deep experience and leadership to this pivotal aspect of the DocTIS project.

We spoke with Dr. Choy about his role in DocTIS, the significance of clinical validation, and how the project could shape the next generation of IMID treatment.

Hello, Ernest! Please, tell us about yourself.

Hello! I am an Emeritus Professor of Rheumatology at Cardiff University in the UK. Growing up, I have always been interested in biological science. After completing my medical training, I started my postgraduate education in London and developed an interest in translational medicine. I was fortunate to get involved in some of the early first-in-man proof of concept clinical trials of monoclonal antibodies in rheumatoid arthritis. Since then, I have continued to conduct research to improve the treatment of chronic inflammatory arthritis.

What initially drew you to the DocTIS project?

Professor Sara Marsal from VHIR and I undertook our postgraduate education at Guy’s Hospital in London at the same time, so we have been friends for many years. When she started discussing the idea of DocTIS with me, I became really excited by the idea of using the latest molecular technologies to try to deliver personalised combination biologic treatments for patients with IMIDs.

What role does your organization play in the DocTIS project?

I am leading on the clinical trial work package with DocTIS as Cardiff has a world class Centre for Trials Research which has expertise in conducting biomarker-based clinical trials using adaptive designs.

What is the key innovation you are contributing to?

We have designed a Simon 2-stage “basket” trial that allows us to assess the efficacy of combining biologic agents in different IMIDs in one clinical trial.   

Regarding your initial expectations, how has the project developed?

Collaborating with talented basic scientists, translational researchers and clinicians in Europe and America has been exciting and rewarding. Our clinical trial design especially the choice of medications and specific IMIDs have been based on results from molecular research undertaken by collaborators. There was also validation of these results in animal models of IMIDs.

What results from the DocTIS project have been most satisfying for you?

The pandemic caused delay and uncertainty. The schedule of the project is tight. Getting regulatory and ethics approvals was a big hurdle. So, getting these approved on time was an achievement, I am very proud of.

The clinical trials have started, what are your expectations?

As a Rheumatologist, I have managed many patients with rheumatoid and psoriatic arthritis. Even though many patients are taking biologic medications, they still have inflammation in their joints. Consequently, they still have to adapt and modify their life as a result. Previous research has shown that remission is important to prevent joints from getting damaged by inflammation. Remission allows patients to function normally, continue to work and have a normal social life. I expect more patients will achieve remission with combination biologic treatment.

How do you think DocTIS will help improve the quality of life of IMID patients in Europe?

IMIDs are common. Quality of life in those affected is poor especially when disease is active. Work, home and social life are significantly impeded unless disease is in remission. Current medications improve disease by reducing inflammation, however, less than a third of patients achieve remission.

What key learnings do you take from the DocTIS collaboration?

The opportunity to collaborate with world leading researchers in molecular science has been a real privilege. I have learnt how they have resolved technical difficulties with innovative approaches. Indeed, they have pioneered new techniques in single cell sequence and informatic analyses. Equally establishing animal models to mimic human IMIDs will have benefits beyond the DocTIS collaboration.

Is there anything about your team you would like to highlight?

I am fortunate to have Dr Philip Pallmann who is instrumental in designing the clinical trial and statistical analysis plan. Mr. Ian Thomas as the senior trial manager was the key reason why we obtained regulatory and ethics approval on schedule.

What are your hopes for the future of DocTIS and IMID therapies?

The DocTIS project may pave the way for other researchers to use the same bench-to-bedside approach, leveraging advanced molecular technologies to deliver personalised medicine selecting the correct combination of medicines for each individual patient.

As Dr. Choy’s reflections show, the strength of DocTIS lies in its collaborative spirit and its bold, translational vision. By uniting academic, clinical, and technological leaders across continents, the consortium is tackling the complexity of IMIDs with unprecedented precision. Coordinated by the Vall d’Hebron Research Institute (VHIR), DocTIS brings together Cardiff University, the University of Verona, Charité – Universitätsmedizin Berlin, the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), the National Center for Genomic Analysis (CNAG), IMIDomics Inc., HudsonAlpha Institute for Biotechnology, and Zabala Innovation — each partner contributing unique expertise to a shared mission of transforming patient care.