Rheumatoid Arthritis Treatment: Cancer Risk Stable, GLP-1 Drugs Show Promise

New Research Offers Reassurance on JAK Inhibitors and Hints at Cardiovascular Benefits

Recent findings presented at the 2025 European Alliance of Associations for Rheumatology (EULAR) congress are providing updated insights into the safety and potential benefits of treatments for rheumatoid arthritis (RA). Studies address concerns about cancer risk with JAK inhibitors and explore the cardioprotective effects of GLP-1 receptor agonists.

Cancer Risk with JAK Inhibitors Remains Largely Unchanged

A large-scale, real-world study involving over 33,000 RA patients revealed no significantly elevated cancer risk among those treated with JAK inhibitors compared to those on biologic disease-modifying anti-rheumatic drugs (bDMARDs). Researchers, including Romain Aymon and colleagues, analyzed data from 13 registers, tracking cancer incidence for up to five years after treatment initiation.

The study identified 53,169 treatment initiations and reported 219 non-melanoma skin cancers and 638 other cancers. While the crude incidence of non-melanoma skin cancer was slightly lower with TNF inhibitors, statistical analysis showed no significant differences in cancer rates between JAK inhibitors and either TNF inhibitors or bDMARDs with other mechanisms of action.

A sub-analysis focused on patients aged 50 and older with cardiovascular risk factors—mirroring the inclusion criteria of the ORAL Surveillance trial—showed a higher cancer incidence across all treatment groups. However, again, no significant difference was found between JAK inhibitors and bDMARDs.

Aymon and team plan further analyses with expanded data sets to strengthen statistical power and evaluate cancer incidence over varying exposure durations. Initial findings, however, are considered reassuring.

Keratinocyte Cancer Risk with JAK Inhibitors Requires Monitoring

Separate research focusing on keratinocyte cancers—primarily basal and squamous cell carcinomas—indicated a potential increased risk with JAK inhibitor use. Analyzing data from the Swedish Rheumatology Quality Register, Viking Huss and colleagues found a 1.72-fold higher hazard ratio for a first keratinocyte cancer diagnosis with JAK inhibitors compared to TNF inhibitors.

“these findings suggest that people with RA treated with a JAKi have a higher incidence of a first keratinocyte cancer, primarily driven by basal cell carcinoma. Additionally – although based on a limited number of events – we saw a higher incidence of a second cancer of this type with JAKi compared to TNFi.”

—Viking Huss

The incidence of keratinocyte cancer is rising in the general population, potentially due to UV exposure and immune alterations. According to the American Academy of Dermatology, an estimated 1 in 5 Americans will develop skin cancer by the age of 70. American Academy of Dermatology

Researchers recommend skin examinations and monitoring for skin cancer risks in patients undergoing JAK inhibitor treatment.

GLP-1 Receptor Agonists May Offer Cardiovascular Protection

Given the cardiovascular risks associated with RA and previous concerns with JAK inhibitors, researchers investigated the potential cardioprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs). Asmaa Beltagy presented findings from a retrospective analysis of over 2,400 RA patients aged 40 and older taking JAK inhibitors.

The study compared patients who subsequently initiated GLP-1RA therapy to those who did not, assessing the incidence of cardiovascular events over five years. Results showed that patients taking GLP-1RAs had a significantly lower risk of acute coronary syndromes and deep venous thrombosis.

While trends toward lower risks of cerebral infarction and peripheral arterial disease were observed, they weren’t statistically significant. Overall, the incidence of cardiovascular events was significantly reduced in the GLP-1RA group.

These findings suggest GLP-1RAs could mitigate certain cardiovascular risks in RA patients treated with JAK inhibitors, but further research is needed to confirm these results.