Why rheumatoid arthritis pain may persist even when inflammation is under control

Date:
September 27, 2026d arthritis can persist even after inflammation improves, with depression, poor sleep, obesity, smoking, and chronic pain potentially helping sustain symptoms. Researchers say identifying these hidden drivers could prevent unnecessary medication changes and lead to more personalized treatment.
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Researchers at Semmelweis University say persistent rheumatic symptoms may be driven by more than inflammation alone. Sleep disorders, depression, obesity, smoking, and other health problems may also help keep symptoms going. In publications in Nature Reviews Rheumatology and The Lancet Rheumatology, the team also introduced a model designed to help doctors identify the underlying causes of symptoms earlier and tailor treatment more effectively.

The researchers examined how depression, smoking, obesity, sleep problems, and other health conditions are connected with difficult-to-treat rheumatoid arthritis.

Rheumatoid arthritis is a chronic autoimmune disease

Rheumatoid arthritis is a chronic autoimmune disease in which the immune system mistakenly attacks the joints, leading to pain, swelling, and stiffness. In Hungary alone, it affects tens of thousands of people. Most patients respond well to treatment, but 6-28 percent fall into the so-called “difficult-to-treat” group because they do not achieve lasting remission despite therapy.

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

A Vicious Cycle of Pain, Mood, and Sleep

Pain and depression, for example, can reduce physical activity, contribute to weight gain, and worsen both sleep and mood. Those changes can then intensify pain and make daily activities more difficult, creating a difficult-to-break “vicious cycle.”

The researchers also developed a new model

The researchers also developed a new model that could improve care for patients whose rheumatoid arthritis remains difficult to manage. Under the widely used “treat-to-target” approach, doctors regularly track measurable indicators of disease activity. If inflammation is not reduced enough, treatment is adjusted, such as by increasing the medication dose or switching to another drug.

The team argues that this same approach can also serve as a kind of “early warning system.” If measurable signs of inflammation improve but symptoms remain, that may indicate the pain or fatigue is not being caused solely, or perhaps at all, by ongoing inflammation.

“When target values improve but the patient still suffers from pain and fatigue, it is worth taking a step back. In such cases, instead of automatically prescribing more medication, doctors should look for what is maintaining the symptoms – whether it is chronic pain syndrome, depression, sleep disorders, or obesity,” said Dr. György Nagy, head of the Department of Rheumatology and Immunology at Semmelweis University.

The researchers say they have seen this approach

The researchers say they have seen this approach improve outcomes in difficult-to-treat patients. In many cases, it may also strengthen the doctor-patient relationship by focusing treatment more closely on what is actually driving the patient’s symptoms.

A Model With Growing International Influence

The team’s model has gained substantial international attention. Publications that introduced the concept of “difficult-to-treat” disease and the related treatment strategy have already been cited more than a thousand times by other researchers.

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

AI Could Help Personalize Treatment

The researchers are now looking toward the next

The researchers are now looking toward the next stage of the work. Alongside their own studies, they plan to participate in projects that use artificial intelligence to develop more effective treatments for people with rheumatoid arthritis.

“With AI-based pattern recognition, we could identify subgroups among patients, and with the help of these data we could create more effective, almost personalized treatment strategies for them,” explained Dr. Lilla Gunkl-Tóth, PhD student at Semmelweis University and first author of the publications.

Materials provided by Semmelweis University. Note: Content may be edited for style and length.

1. Lilla Gunkl-Tóth, Iain B. McInnes, György Nagy. Bridging the gap: combining treat-to-target and difficult-to-treat strategies in the management of rheumatoid arthritis. Nature Reviews Rheumatology, 2026; 22 (5): 319 DOI: 10.1038/s41584-026-01354-w
2. Wenhui Xie, Tong Chen, Yuan Chen, Zhuoli Zhang, Shiyu Xiao. Associated lifestyle factors and comorbidities of difficult-to-treat rheumatoid arthritis: a systematic review and meta-analysis. The Lancet Rheumatology, 2026; 8 (6): e425 DOI: 10.1016/S2665-9913(26)00041-X
3. Lilla Gunkl-Tóth, György Nagy. Lifestyle factors in difficult-to-treat rheumatoid arthritis. The Lancet Rheumatology, 2026; 8 (6): e408 DOI: 10.1016/S2665-9913(26)00108-6

Semmelweis University. “Why rheumatoid arthritis pain may persist even when inflammation is under control.” ScienceDaily. ScienceDaily, 27 September 2026. <www.sciencedaily.com/releases/2026/09/260925093208.htm>.
Semmelweis University. (2026, September 27). Why rheumatoid arthritis pain may persist even when inflammation is under control. ScienceDaily. Retrieved September 27, 2026 from www.sciencedaily.com/releases/2026/09/260925093208.htm
Semmelweis University. “Why rheumatoid arthritis pain may persist even when inflammation is under control.” ScienceDaily. www.sciencedaily.com/releases/2026/09/260925093208.htm (accessed September 27, 2026).

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