New research presented at the EULAR 2025 Congress provided updated real-world data on cancer and cardiovascular risks associated with Janus kinase inhibitors in patients with rheumatoid arthritis.
The studies addressed safety concerns following prior reports of elevated malignancy risk with Janus kinase inhibitors (JAKi) compared to tumor necrosis factor inhibitors (TNFi).
In one large study, investigators analyzed cancer incidence using data from 13 patient registries, including 53,169 treatment initiations involving 33,127 patients. During follow-up, 219 cases of nonmelanoma skin cancers (NMSC) and 638 cases of other cancers were recorded. The crude incidence of non-NMSC cancers was 2.2 per 1,000 patient-years for TNFi, 2.9 per 1,000 person-years for JAKi, and 3.1 per 1,000 person-years for biologics with other mechanisms of action (OMA). After adjustment, there were no statistically significant differences in cancer risk between JAKi and TNFi for cancers, excluding NMSC, (adjusted incidence rate ratio [IRR] = 1.10, 95% confidence interval [CI] = 0.89–1.37) or NMSC (adjusted IRR = 1.12, 95% CI = 0.78–1.60); as well as between JAKi and OMA, with a respective (adjusted IRR = 1.07, 95% CI = 0.86–1.32) and (adjusted IRR = 0.79, 95% CI = 0.54–1.15).
A subgroup analysis examined patients aged 50 years and older with at least one cardiovascular risk factor, representing 39.4% of treatment courses. Cancer incidence rates in this group were 3.2, 4.2, and 4.1 per 1,000 patient-years for TNFi, JAKi, and OMA, respectively. No statistically significant differences in cancer incidence were observed between groups.
Additional data evaluated keratinocyte cancer risk, including basal cell and squamous cell carcinoma, using data from over 21,000 patients with RA in Sweden. The investigators identified 94 keratinocyte cancers among JAKi users, 407 among OMA users, and 628 among TNFi users. Compared with TNFi, JAKi users had a 72% increased risk of developing a first keratinocyte cancer. Among patients with prior keratinocyte cancer, JAKi users had a 176% higher risk of developing a second keratinocyte cancer compared with TNFi users. The risk was also elevated in OMA users, but to a lesser extent.
The increased keratinocyte cancer risk associated with JAK inhibitors appeared primarily driven by basal cell carcinoma. These findings supported skin monitoring among patients treated with JAKi, especially those with a history of skin cancer.
A separate retrospective analysis evaluated cardiovascular outcomes in patients with RA aged over 40 years receiving JAK inhibitors. Investigators included 2,449 patients, some of whom initiated glucagon-like peptide (GLP)-1 receptor agonists (RA). Over 5 years, patients receiving GLP-1 RAs had significantly lower incidences of acute coronary syndromes and deep venous thrombosis compared with those not receiving GLP-1 RAs. There were nonsignificant trends toward lower risks of cerebral infarction and peripheral arterial disease. Median survival didn't differ significantly between the groups.
The investigators concluded that JAKi didn't significantly increase overall cancer incidence in patients with RA compared with other biologics. However, the elevated keratinocyte cancer risk warranted continued dermatologic monitoring. The addition of GLP-1 RAs may offer cardiovascular benefits, but further research is needed to confirm these findings.
Source: EULAR
