JAK Inhibitors After Biologic Therapy in Atopic Dermatitis: Clinical Lessons From JADE EXTEND and Real-World Studies

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The JADE DARE and JADE EXTEND clinical trials demonstrated the superior efficacy of abrocitinib, an oral Janus kinase (JAK) inhibitor, compared with dupilumab in treating atopic dermatitis. In the head-to-head comparison, abrocitinib 200 mg daily outperformed dupilumab (600 mg induction, 300 mg maintenance every 14 days) through week 26. The study design included a unique switch component where dupilumab nonresponders transitioned to abrocitinib after a 4-week washout period.

The switching results were particularly impressive, with 77% of dupilumab nonresponders achieving at least EASI-75 after just 12 weeks on abrocitinib 200 mg daily. This finding aligns with network meta-analyses showing JAK inhibitors consistently outperform biologics in both skin clearance and itch relief. The broad anti-inflammatory mechanism of JAK inhibitors appears to provide superior therapeutic benefits compared with the more targeted approach of biologics like dupilumab.

Real-world evidence from studies including the Canadian Heart Failure (CAN-HF) Registry and OPTIMIZE-HF and the JADE EXTEND study reinforces these clinical trial findings. The CAN-HF study showed 66% of dupilumab failures achieved an Investigator Global Assessment score of 0 to 1 within 4 months on upadacitinib. Real-world registries demonstrate that JAK inhibitors maintain efficacy across diverse patient populations, including those with cardiovascular comorbidities and other risk factors typically excluded from clinical trials. The flexibility of JAK inhibitor dosing allows for both up-titration and down-titration based on patient response, enabling personalized treatment approaches.