Why some rheumatoid arthritis cases are difficult to treat

Researchers examined how depression, smoking, obesity, sleep disorders, and other health conditions are associated with hard-to-treat rheumatoid arthritis.

Rheumatoid arthritis is a chronic autoimmune disease in which the immune system mistakenly attacks the joints, causing pain, swelling, and stiffness. Tens of thousands of people are affected in Hungary alone. Most patients respond well to treatment, but between 6% and 28% do not achieve durable remission despite treatment. These patients are considered part of the “hard-to-treat” group.

According to the research published in Nature Reviews Rheumatology and The Lancet Rheumatology, these additional health issues may do more than occur alongside rheumatoid arthritis. They may also contribute to keeping symptoms active.

The vicious cycle of pain, mood, and sleep

Pain and depression can reduce physical activity, contribute to weight gain, and worsen both sleep and mood. These changes can intensify pain and make daily life more difficult, creating a “vicious cycle” that is difficult to break.

Researchers have also developed a model that could improve care for patients whose rheumatoid arthritis remains difficult to manage. Under the widely used “treat-to-target” approach, doctors regularly monitor measurable indicators of disease activity. If inflammation is not reduced sufficiently, treatment may be adjusted by increasing the dose of a medication or switching to a different drug.

The researchers argue that this approach can also serve as an early warning system. If measurable signs of inflammation improve but symptoms remain, it may indicate that pain and fatigue are not caused solely by ongoing inflammation, or that other factors are maintaining the symptoms.

Why doctors may need to look beyond inflammation

“If targets have improved but the patient is still suffering from pain or fatigue, it’s worth taking a step back. In such cases, doctors should not automatically prescribe more drugs, but rather look for reasons that are maintaining the symptoms, such as chronic pain syndromes, depression, sleep disorders, or obesity,” said Dr. György Nagy, chair of the Department of Rheumatology and Immunology at Semmelweis University.

Researchers say this approach has improved outcomes for difficult-to-treat patients. In many cases, focusing treatment on the factors actually causing or maintaining a patient’s symptoms may also strengthen the doctor-patient relationship.

A rheumatoid arthritis model with international influence

The team’s model has attracted significant international attention. Publications introducing the concept of “hard-to-treat” diseases and related treatment strategies have already been cited more than 1,000 times by other researchers.

The definition is now used worldwide, not only in rheumatoid arthritis research but also in discussions of other diseases.

How AI could personalize rheumatoid arthritis treatment

The researchers are now moving toward the next stage of their work. Alongside their current research, they will participate in a project using artificial intelligence to develop more effective treatments for patients with rheumatoid arthritis.

“AI-based pattern recognition allowed us to identify subgroups of patients, and with the help of these data we were able to create more effective and almost personalized treatment strategies for patients,” explained Dr. Lila Gunkl Toth, a doctoral student at Semmelweis University and lead author of the publication.