Upadacitinib tied to better survival vs tofacitinib in MDA5+DM-ILD

Upadacitinib demonstrates its noninferiority to tofacitinib in improving lung transplantation-free survival (LTFS) at 6 months among patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease (MDA5⁺DM-ILD), reports a study.

Upadacitinib and tofacitinib were administered to 106 and 328 eligible patients, respectively. At 6 months, the corresponding crude LTFS rates were 71.7 percent (76/106) and 67.4 percent (221/328).

In the inverse probability treatment weighting (IPTW)-adjusted cohort, treatment with upadacitinib resulted in higher survival compared with tofacitinib (p=0.067). The weighted risk difference was 10.3 percent (95 percent confidence interval, ‒0.4 to 20.2), meeting the noninferiority margin (p=0.003).

The results persisted in sensitivity and subgroup analyses, with potentially greater benefit of upadacitinib among incident users of JAK inhibitors (as first-line treatment), monotherapy recipients (without combination with other immunosuppressants except steroid), and those with rapidly progressive ILD.

No significant between-group differences were observed in safety profiles.

“Upadacitinib was found to be noninferior to tofacitinib in improving 6-month LTFS among patients with MDA5⁺DM-ILD, with comparable safety,” the investigators said.

The treatment of MDA5⁺DM-ILD remains challenging. To address this, a multicentre cohort study was conducted in China, involving MDA5⁺DM-ILD patients treated from January 2020 to February 2025. The investigators implemented prevalent/incident new users and noninferior design, together with inverse IPTW to emulate a randomized controlled trial.