# Dual effects of JAK vs TNF inhibitors on osteoporosis, fractures and mortality in rheumatoid arthritis: a real-world cohort study

## TL;DR

This study found that JAK inhibitors may reduce osteoporosis risk but increase mortality in rheumatoid arthritis patients compared to TNF inhibitors.

## Contribution

The study provides real-world evidence of the dual effects of JAKi versus TNFi on bone health and mortality in RA patients.

## Key findings

- JAKi use was associated with lower risk of osteoporosis compared to TNFi.
- JAKi use was linked to higher all-cause mortality compared to TNFi.
- Fracture risk reduction was not clearly observed with JAKi use.

## Abstract

This real-world study compared the effects of JAK inhibitors (JAKi) versus TNF inhibitors (TNFi) on bone health and survival in rheumatoid arthritis (RA) patients.

We conducted a retrospective cohort study using the collaborative electronic health records (EHR) database network (2016-2024). After 1:1 propensity score matching, 16, 572 JAKi and 16, 572 TNFi users were included, with follow-up for up to 5 years. Primary outcomes were a composite of “any fracture or osteoporosis, ” individual fracture and osteoporosis events, and all-cause mortality.

In the propensity score–matched cohort, JAKi use was associated with a lower risk of the composite outcome (HR = 0.930) and osteoporosis (HR = 0.906) compared with TNFi. However, a reduction in fracture risk was not clearly observed. JAKi use was also associated with higher all-cause mortality (HR = 1.582). Subgroup estimates suggested potential heterogeneity, but these findings were exploratory.

In this large EHR-based cohort, JAKi initiation was associated with lower rates of osteoporosis-related outcomes but higher all-cause mortality compared with TNFi. Given the observational design, potential residual confounding, and limited follow-up for many patients, these findings should be interpreted as associations and warrant confirmation in other datasets and prospective studies.

To compare real-world associations of JAKi vs TNFi with bone outcomes and all-cause mortality in RA.

In a propensity score–matched cohort, JAKi use was associated with lower osteoporosis-related outcomes but higher all-cause mortality compared with TNFi.

These observational findings suggest a potential trade-off and highlight the need for individualized risk–benefit discussions and confirmation in other datasets/prospective studies.