Background Patients with rheumatoid arthritis (RA) have excess cardiovascular risk, and cardiovascular safety concerns surrounding Janus kinase inhibitors (JAKi) make acute coronary event assessment clinically important. Real-world analyses are difficult because treatment selection, sparse events, and complete separation can distort conventional regression. We evaluated treatment-specific acute coronary event patterns in a single-center RA cohort using sparse-data and balance-oriented methods. Methods We performed a retrospective study of 316 RA patients. The primary exposure was JAKi treatment; non-JAKi treatment included TNFi or csDMARD regimens, although the pooled comparator was predominantly csDMARD-only therapy. The primary outcome was a recorded acute coronary event (acute myocardial infarction [AMI] or unstable angina), with a definite-AMI sensitivity analysis. We used exact event-rate estimation, Firth bias-reduced logistic regression, overlap-weighted propensity-score diagnostics with effective sample size estimation, Bayesian beta-binomial zero-event shrinkage, and tipping-point analysis. Missingness was limited to 2 HDL-C values and 1 BMI value (0.6% and 0.3%). Results Among 316 patients, 115 received JAKi and 201 received non-JAKi therapy; 190 of 201 non-JAKi patients received csDMARD-only therapy. Acute coronary events occurred in 0/115 JAKi-treated patients, 2/11 TNFi-treated patients, and 87/190 csDMARD-treated patients (exact 95% CI for JAKi: 0.0%–3.2%). In the clinically adjusted Firth model, JAKi exposure was associated with lower odds of an acute coronary event (OR 0.022, 95% CI 0.001–0.344; P = 0.007). The overlap-weighted effective sample size was 215.5 overall (100.7 JAKi; 115.8 non-JAKi), with a largest post-weighting standardized mean difference of 0.053 and a weighted risk difference of − 16.4 percentage points. Marginal standardization of the clinical Firth model yielded model-predicted event probabilities of 9.5% under JAKi exposure and 32.1% under non-JAKi exposure. Bayesian analysis estimated a posterior median JAKi event rate of 0.20% (95% credible interval 0.0004%–2.16%). Thirty-eight hypothetical JAKi events were required before the exact comparison became non-significant. Conclusions In this cohort, JAKi exposure identified a selected RA subgroup with a zero-event acute coronary pattern across multiple sparse-data analyses. These findings should not be interpreted as causal cardioprotection; rather, they support transparent reporting of treatment selection, baseline cardiovascular phenotype, and absolute-risk summaries in real-world JAKi safety studies. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points • This retrospective study used sparse-data methods and overlap-weighted diagnostics to address zero acute coronary events among JAKi-treated patients in a real-world RA cohort. • Missingness in model covariates was minimal: 2 HDL-C values and 1 BMI value were missing (0.6% and 0.3%), with no variable exceeding 5% missingness. • The primary binary comparison was dominated by csDMARD-treated patients in the non-JAKi group; TNFi estimates were exploratory because only 11 patients received TNFi therapy. • Absolute-risk summaries were added: the overlap-weighted risk difference was − 16.4 percentage points, and clinical Firth model-predicted probabilities were 9.5% under JAKi exposure and 32.1% under non-JAKi exposure. </entry> </row> </tbody> </tgroup> </Table>

Janus kinase inhibitor exposure and acute coronary event patterns in rheumatoid arthritis: a treatment-aware retrospective study

期刊论文
发表日期：

2026年7月24日

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Yuwei Wang,
Leina Sun,
Ruohan Yu,
Weiduo Nie,
Sheng-Guang Li,
Fangcheng Su,
Fang Cheng,
Di Jin

摘要

Background

Patients with rheumatoid arthritis (RA) have excess cardiovascular risk, and cardiovascular safety concerns surrounding Janus kinase inhibitors (JAKi) make acute coronary event assessment clinically important. Real-world analyses are difficult because treatment selection, sparse events, and complete separation can distort conventional regression. We evaluated treatment-specific acute coronary event patterns in a single-center RA cohort using sparse-data and balance-oriented methods.

Methods

We performed a retrospective study of 316 RA patients. The primary exposure was JAKi treatment; non-JAKi treatment included TNFi or csDMARD regimens, although the pooled comparator was predominantly csDMARD-only therapy. The primary outcome was a recorded acute coronary event (acute myocardial infarction [AMI] or unstable angina), with a definite-AMI sensitivity analysis. We used exact event-rate estimation, Firth bias-reduced logistic regression, overlap-weighted propensity-score diagnostics with effective sample size estimation, Bayesian beta-binomial zero-event shrinkage, and tipping-point analysis. Missingness was limited to 2 HDL-C values and 1 BMI value (0.6% and 0.3%).

Results

Among 316 patients, 115 received JAKi and 201 received non-JAKi therapy; 190 of 201 non-JAKi patients received csDMARD-only therapy. Acute coronary events occurred in 0/115 JAKi-treated patients, 2/11 TNFi-treated patients, and 87/190 csDMARD-treated patients (exact 95% CI for JAKi: 0.0%–3.2%). In the clinically adjusted Firth model, JAKi exposure was associated with lower odds of an acute coronary event (OR 0.022, 95% CI 0.001–0.344; P = 0.007). The overlap-weighted effective sample size was 215.5 overall (100.7 JAKi; 115.8 non-JAKi), with a largest post-weighting standardized mean difference of 0.053 and a weighted risk difference of − 16.4 percentage points. Marginal standardization of the clinical Firth model yielded model-predicted event probabilities of 9.5% under JAKi exposure and 32.1% under non-JAKi exposure. Bayesian analysis estimated a posterior median JAKi event rate of 0.20% (95% credible interval 0.0004%–2.16%). Thirty-eight hypothetical JAKi events were required before the exact comparison became non-significant.

Conclusions

In this cohort, JAKi exposure identified a selected RA subgroup with a zero-event acute coronary pattern across multiple sparse-data analyses. These findings should not be interpreted as causal cardioprotection; rather, they support transparent reporting of treatment selection, baseline cardiovascular phenotype, and absolute-risk summaries in real-world JAKi safety studies.

Key Points

• This retrospective study used sparse-data methods and overlap-weighted diagnostics to address zero acute coronary events among JAKi-treated patients in a real-world RA cohort.

• Missingness in model covariates was minimal: 2 HDL-C values and 1 BMI value were missing (0.6% and 0.3%), with no variable exceeding 5% missingness.

• The primary binary comparison was dominated by csDMARD-treated patients in the non-JAKi group; TNFi estimates were exploratory because only 11 patients received TNFi therapy.

• Absolute-risk summaries were added: the overlap-weighted risk difference was − 16.4 percentage points, and clinical Firth model-predicted probabilities were 9.5% under JAKi exposure and 32.1% under non-JAKi exposure.