Christopher G. Bunick, MD, PhD

Panelists discuss how to effectively onboard patients to Janus kinase (JAK) inhibitors through transparent risk discussions, early follow-up visits at 4 weeks, and personalized treatment approaches that consider patient-reported outcomes and the “3 Cs” (cancer, cardiac disease, clotting disease) while emphasizing the anti-inflammatory benefits and quality-of-life improvements these therapies provide.

Personalized Strategies for Sequencing Therapies in Atopic Dermatitis

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Patient onboarding for JAK inhibitor therapy requires comprehensive counseling focused on realistic expectations and anticipatory guidance. Clinicians should provide transparent discussion of the boxed warning while contextualizing risks within the atopic dermatitis–specific safety data. The “3 Cs” assessment framework—evaluating patient history of cancer, cardiac disease, and clotting disorders—helps guide appropriate patient selection while recognizing that many patients with comorbidities can safely receive JAK inhibitors based on current evidence.

Effective patient communication emphasizes the anti-inflammatory properties of JAK inhibitors, drawing parallels to familiar medications such as ibuprofen to contextualize safety concerns. Early follow-up at 4 weeks demonstrates physician commitment and allows for treatment optimization, as JAK inhibitors typically show rapid efficacy that often exceeds patient expectations. Continued emphasis on fundamental atopic dermatitis skin care principles remains essential even with systemic therapy success.

The evolving landscape of atopic dermatitis treatment now enables truly personalized approaches based on patient-reported outcome measures and quality-of-life impacts. Current treatment guidelines support switching therapies when patients don’t achieve moderate improvement within 3 to 6 months, moving away from stepwise approaches and toward optimization of individual patient outcomes. This patient-centric model recognizes that JAK inhibitors address multiple symptom domains simultaneously—including itch, sleep disruption, and psychosocial impacts—making them suitable for diverse patient presentations while maintaining the core principle of treating patients as family members deserving optimal care.

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Panelists discuss how Janus kinase (JAK) inhibitors demonstrate a favorable safety profile across age groups and comorbid populations, with potential cardioprotective benefits due to their anti-inflammatory effects, while addressing common concerns about the boxed warning by emphasizing that only herpes zoster reactivation, tuberculosis, and nonmelanoma skin cancer show increased rates across all indications.

Understanding the Safety Profile of Oral JAK Inhibitors in Atopic Dermatitis

Oral JAK inhibitors demonstrate an extensive safety profile across multiple age groups and indications, with upadacitinib approved for use in patients as young as 2 years for juvenile idiopathic arthritis and in older populations (mean age, 71 years) for giant cell arteritis. Despite FDA boxed warnings applied to all JAK inhibitors, comprehensive safety analyses of more than 9000 patient-years reveal that only herpes zoster reactivation, tuberculosis, and nonmelanoma skin cancer show statistically significant increased rates across all 9 approved indications.

Emerging evidence suggests potential cardioprotective benefits of JAK inhibitors in patients with atopic dermatitis. Recent analyses demonstrate that patients with atopic dermatitis who are on JAK inhibitors have lower rates of major adverse cardiovascular events (MACEs) and venous thromboembolism (VTE) compared with both the general population and patients with untreated atopic dermatitis. This cardioprotective effect likely stems from the systemic anti-inflammatory properties of JAK inhibitors, addressing the underlying inflammatory burden that contributes to cardiovascular risk in atopic dermatitis.

Multiple targeted safety studies have addressed specific concerns, including analyses of JAK inhibitor use in women on oral contraceptives (showing no increased VTE risk), smokers (no increased MACEs, VTE, or malignancy risk), and geriatric populations (no increased adverse events). The most common manageable adverse effects include mild acne (approximately 10% of patients) and the need for routine monitoring, including annual skin cancer surveillance, shingles vaccination, and tuberculosis screening with QuantiFERON testing.

Panelists discuss how abrocitinib demonstrated superior efficacy compared with dupilumab in head-to-head trials, with 77% of dupilumab nonresponders achieving Eczema Area and Severity Index 75 (EASI-75) after switching to abrocitinib for 12 weeks, supported by real-world registry data showing consistent outcomes across diverse patient populations.

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

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.

Panelists discuss how the Level Up study demonstrated that patients who didn’t achieve Eczema Area and Severity Index 75 (EASI-75) on dupilumab could be successfully switched to upadacitinib without washout, with two-thirds achieving EASI-75 and one-third achieving EASI-90 within just 4 weeks of switching.

Switching From a Biologic to Upadacitinib in Atopic Dermatitis: Key Learnings From the Level Up Study

The Level Up study provided crucial real-world evidence for switching from dupilumab to upadacitinib in patients with inadequate biologic response. In the head-to-head comparison, upadacitinib demonstrated superior efficacy in achieving the primary end point of simultaneous EASI-90 and an itch score of 0 to 1 at week 16. Most significantly, patients who didn’t achieve EASI-75 on dupilumab (averaging only 50% improvement) were switched to upadacitinib 15 mg without a washout period.

The switch population showed remarkable improvement, with two-thirds achieving EASI-75 and one-third achieving EASI-90 within just 4 weeks of switching. By week 16 post switch, 80% achieved EASI-75 and 60% achieved EASI-90, with nearly 30% reaching minimal disease activity (simultaneous EASI-90 and itch 0-1). Importantly, most of the patients-maintained response on the lower 15-mg dose, though dose escalation to 30 mg was available for nonresponders at week 4.

The study’s design reflects real-world clinical practice with immediate switching without washout periods, avoiding unnecessary disease flare during transition. These results demonstrate that patients with poor biologic response can achieve substantial improvement with Janus kinase inhibitors, often experiencing deeper skin clearance and more robust itch reduction than previously achieved. The durability of response extends beyond 140 weeks based on published data, providing sustained disease control without neutralizing antibody concerns associated with biologic therapies.

Christopher G. Bunick, MD, PhD

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