Increased VTE Risk with Baricitinib Save

The RA-BRIDGE and RA-BRANCH studies were presented as a late-breaking abstract at EULAR 2026 (LB0009). This was the pooled results from two large FDA post-marketing commitment safety trials — RA-BRIDGE (global) and RA-BRANCH (US-only) — comparing baricitinib (BARI) at 2 mg and 4 mg daily against TNF inhibitors (etanercept or adalimumab) in RA patients specifically enriched for venous thromboembolic event (VTE) risk factors.

The trials randomized 3,640 patients 1:1:1 to BARI 2 mg, BARI 4 mg, or TNFi, with up to ~6 years on-treatment exposure totaling 11,524 patient-years. Patients were required to have at least one VTE risk factor (prior VTE, age ≥60, BMI ≥30, or age 50–59 with BMI 25–29) to be enrolled. The primary endpoint was time to first adjudicated VTE, with a non-inferiority (NI) margin of 1.8 (upper 95% CI of HR). The trials closed early after 82 of 123 pre-specified VTE events were accrued, as further events would not have altered the results. 

The analysis showed that non-inferiority was not met, as the pooled BARI (2 mg & 4 mg) patients had 62 VTE events (2.5%) versus 20 (1.7%) in the TNFi group. The incidence rate was 0.79/100 PY for BARI combined versus 0.51/100 PY for TNFi. The hazard ratio was 1.606 (95% CI 0.969–2.660), with the upper CI exceeding the pre-specified NI margin of 1.8 — thus non-inferiority was not demonstrated (meaning there were more VTE events with BARI than with TNFi. No dose-dependent pattern was observed.

Other Safety Endpoints
While these results confirmed the increased VTE risk seen in the ORAL SURVEILLANCE study, MACE (HR 1.06), malignancy (1.32), all-cause mortality (HR 0.97), arterial thromboembolism (HR 1.27), and opportunistic infections (HR 1.25) showed no statistically significant differences between BARI and TNFI, with confidence intervals crossing 1.0. Serious infections were nominally more frequent with baricitinib (IR 3.17 vs. 2.46/100 PY).

Efficacy 
Exploratory analysis of the RA-BRIDGE cohort showed BARI 4 mg to be superior to TNFi at week 52 for ACR70, CDAI remission, and DAS28 remission outcomes. BARI 2 mg was nominally inferior to TNFi.

In this VTE-enriched RA population, baricitinib was not non-inferior to TNF inhibitors for VTE risk, with an approximately 60% higher relative hazard that did not reach statistical significance. Importantly, BARI was non-inferior to TNF inhibitors for MACE, malignancy, arterial thrombosis, and opportunistic infection (but not serious infections).

Like the ORAL SURVEILLANCE study that was also enriched in high risk patients, these data confirm the higher risk of VTE with JAK inhibitors, but question whether JAK inhibitors raise the risk on mortality, MACE and malignancy.

Editor's note: Watch an interview about this study with Dr. Jon Giles