Abstract Rationale MDA5-dermatomyositis-associated interstitial lung disease (MDA5-DM-ILD) carries high early mortality. Tofacitinib is increasingly used off-label, yet comparative real-world data remain limited. Methods We performed a retrospective cohort analysis of de-identified electronic health records in the TriNetX Research Network. Adults with MDA5-DM and interstitial lung disease were categorized by exposure to tofacitinib (exposed) versus no tofacitinib (unexposed). Patients with the outcome prior to the analysis window were excluded (10 exposed; 35 unexposed). The primary outcome was all-cause mortality. TriNetX generated cumulative risk metrics (risk difference, risk ratio, odds ratio) and time-to-event outputs, including Kaplan-Meier (KM) curves with the log-rank test and a Cox model hazard ratio (HR); proportional hazards were assessed by the platform’s diagnostic. Results After exclusions, 297 patients received tofacitinib and 9,339 did not; deaths occurred in 42 and 1,897 patients, respectively. Cumulative risk of death was 14.14% with tofacitinib versus 20.31% without (absolute risk difference −6.17%, 95% CI − 10.22% to − 2.13%; p = 0.009, z = −2.612). The risk ratio was 0.696 (95% CI 0.525-0.924), and the odds ratio 0.646 (95% CI 0.464-0.899). In KM analysis, survival probability at the end of the time window was 66.06% with tofacitinib versus 25.59% without; median survival was not reached with tofacitinib and 6,623 days without. The log-rank test was not significant (chi-square = 0.502; p = 0.479), and the Cox HR was 1.117 (95% CI 0.822-1.519), with no violation of proportional hazards (chi-square = 0.029; p = 0.865). The absolute risk difference corresponds to an approximate number needed to treat (NNT) of 16 over the observed period. Conclusions In this multi-institutional, real-world cohort of MDA5-DM-ILD, tofacitinib exposure was associated with a significantly lower cumulative risk of death (RR 0.70) compared with no tofacitinib, whereas time-to-event analyses (log-rank test and Cox HR) were not statistically significant. These findings suggest a potential survival benefit of tofacitinib and support confirmation with adjusted analyses and prospective studies. This abstract is funded by: N/A
Alwarawrah et al. (Fri,) studied this question.