Over the last 20 years, advancements in drug treatments for rheumatoid arthritis (RA) have enabled many to live without pain, joint swelling, and long-term disability. However, for numerous patients in Europe, finding the right medication still involves lengthy trial and error.
To address this, researchers, clinicians, and patients from seven EU nations, alongside Norway, Switzerland, and the UK, have collaborated in an EU-funded initiative named SQUEEZE.
Instead of seeking new RA medications, the aim is to optimize the use of existing ones and discover new biological markers to guide treatment, enhancing patient safety and efficacy.
Professor Dr. Daniel Aletaha from the Medical University of Vienna, coordinating the five-year initiative, treats RA patients at Vienna General Hospital’s rheumatology center.
“We have many effective therapies that can control rheumatoid arthritis, but we still don’t get enough patients into remission. The challenge is no longer only to develop new drugs – it is to maximize the impact of the ones we already have,” he explained.
RA is a chronic autoimmune condition where the immune system attacks joints, causing pain, stiffness, inflammation, and fatigue. It typically affects individuals aged 30 to 60, who are often managing families and careers.
Without specific guidance on how a medication will work for each patient, treatment decisions may seem like educated guesswork. Patients might switch between medications frequently, each change bringing new concerns about side effects and safety.
“That uncertainty is frustrating for patients and doctors alike,” said Aletaha.
Achieving remission more quickly, when symptoms are significantly reduced or disappear, means less pain, less fatigue, and a lower risk of permanent joint damage.
The main focus for SQUEEZE researchers is identifying biomarkers: measurable indicators of a biological state or condition that can help doctors select the right drug for the right person.
Researchers are studying tissue samples from affected joints to determine if biomarkers at the site of inflammation can predict which therapy will be most effective for an individual patient. They are also examining levels of the harmless but prevalent torque teno virus in the blood as a real-time indicator of immune system suppression.
Viral levels fluctuate with the intensity of treatment. Monitoring these levels could help doctors identify the balance where drugs are powerful enough to control the disease but not so strong that they raise the risk of infection.
Optimizing drug dosage and delivery is another focus, ensuring each drug is used optimally. Some project studies are assessing if patients in stable remission can safely reduce the dose of expensive biologic drugs, decreasing side effects and healthcare costs.
Others investigate whether changing how a medicine is taken, such as injecting methotrexate instead of oral administration, can enhance its effectiveness by improving absorption.
By pooling thousands of samples from across Europe, researchers are creating shared datasets reflecting diverse health systems.
“A person with rheumatoid arthritis is dealing with drugs, disease, human interactions with doctors, nurses – all that plays into a successful outcome,” said Aletaha.
Even the most effective therapy is ineffective if not taken as prescribed. Yet starting, taking, and continuing treatment over time is a significant challenge in chronic diseases.
Dr. Agnes Kocher from Professor Dr. Sabina De Geest’s team at the University of Basel in Switzerland is developing a digital, integrated care model using secure online tools to support patients between clinic visits and understand why some patients switch drugs frequently.
“At the moment, as clinicians, if we see that the disease is not well controlled, we do not know if it’s because of the drug not working well, or whether adherence is the problem,” Kocher said.
The SQUEEZE care model combines medical and behavioral support to help patients manage their medication in real-world settings.
Through electronic questionnaires linked to a national patient registry, the system identifies people at low, medium, or high risk of non-adherence and the factors driving that risk. These range from fear of injections and side effects to difficulty obtaining repeat prescriptions or managing treatment regimens alongside other medications.
The response is tailored to each patient, with ongoing support from the care team based on their risk level and individual needs. A patient missing a weekly dose due to a family event might be helped to adjust the timing. Someone anxious about injections may receive extra support from a specialist nurse.
Importantly, the model facilitates open conversations. “Patients often tell us they don’t want to admit to their doctor that they struggle with treatment because they don’t want to be seen as a ‘bad patient’,” said Kocher.
Nurses may sometimes be better positioned for patients to confide in, as they often spend more time with them and can build a personal rapport.
The Basel team hopes the new care model will improve doctor-patient conversations by guiding pertinent questions and enabling shared treatment decisions.
“Changing treatments creates a lot of uncertainty. There is the fear of returning to square one and their symptoms worsening under a new treatment, or more side effects, or running out of options.”
The contribution of RA patients and groups is a noteworthy aspect of SQUE
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