Can Upadacitinib Provide Long-Term Relief and Safety for Atopic Dermatitis in Real-World Settings?

by Haroon Ahmad, MD 2025-01-01 00:00

PhysicianMedical

🔍 Key Finding This real-world study demonstrated sustained effectiveness of upadacitinib for atopic dermatitis through 48 weeks, with significant improvements in disease severity measures and a comparable response between 15mg and 30mg doses. Upadacitinib offered dose flexibility, allowing adjustments based on individual patient needs and potential side effects, which proved advantageous in a real-world setting.

🔬 Methodology Overview

Design: Prospective, real-world, observational study.
Setting: 15 Italian dermatological centers.
Participants: 146 adult patients with moderate-to-severe atopic dermatitis (AD) unresponsive, intolerant, or with contraindications to approved systemic therapies (cyclosporine and dupilumab).
Intervention: Upadacitinib 15 mg or 30 mg daily, prescribed based on physician decision within a compassionate use program.
Data Collection: Baseline characteristics, disease severity assessments (EASI, BSA, DLQI, POEM, NRS subtests) at baseline and every 16 weeks (with slight variations), safety assessments (physical examination and laboratory tests).
Statistical Analysis: Within-patient comparisons of continuous scores using the Wilcoxon test, percentage of patients achieving EASI 75/90/100 at weeks 16, 32, and 48, logistic regression analysis to assess the effect of different upadacitinib doses on EASI responses.

📊 Results

Study Population: 146 adult patients with moderate-to-severe atopic dermatitis (AD) unresponsive, intolerant, or with contraindications to approved systemic therapies (mostly cyclosporine and dupilumab). Mean baseline EASI score was 25 ± 11.2 and mean DLQI was 16.3 ± 8.6.
Treatment: Upadacitinib 15mg or 30mg daily, primarily as monotherapy (127/146, 87.0%). Initial dosing was 30mg for 118 patients (80.8%) and 15mg for 28 patients (19.2%). Dose adjustments (reduction or escalation) occurred in 38 patients (26%).
Efficacy: Significant improvement in EASI score by Week 16 (mean EASI 5.4 ± 7.9, mean percentage reduction 78.4%) and sustained through Week 48. EASI 75, 90, and 100 responses at Week 48 were 87.6%, 69.1%, and 44.3%, respectively. Significant improvements also observed in BSA, itch-NRS, sleep-NRS, pain-NRS, DLQI, and POEM scores through Week 48. Comparable responses seen in both 15mg and 30mg initial dose groups.
Safety: 26 of 146 patients (17.8%) experienced at least one adverse event (AE). A total of 30 AEs were recorded, mostly mild to moderate. Four AEs (acute myocardial infarction, thrombophlebitis, limb swelling/pain, and hematuria) led to treatment discontinuation in 4 patients. Infections were the most common AE category (9/30, 30.0%). Seven AEs (26.7%) were laboratory abnormalities. Dropouts totaled 7/146 (4.8%).
Dose Interruption: Temporary treatment suspension (mostly due to COVID-19 vaccination) occurred in 12 patients (8.2%). Re-treatment after suspension maintained therapeutic response in 8/12 (66.7%) cases.

💡 Clinical Impact This research demonstrates upadacitinib’s sustained effectiveness and acceptable safety profile in real-world moderate-to-severe AD patients, including those who failed previous systemic therapies, over 48 weeks. The demonstrated dose flexibility of upadacitinib allows clinicians to tailor treatment to individual patient needs and potentially optimize the risk/benefit ratio while managing drug costs.

🤔 Limitations

Limited long-term safety data for JAK inhibitors, especially regarding cardiovascular risk, venous thromboembolism, and malignancy.
Potential under-reporting of adverse events, especially those occurring after the initial 16 weeks.
Small sample size of the 15 mg upadacitinib treatment group and the potential for dose escalation in this group, limiting the comparison between the 15 mg and 30 mg doses.
Not all patients completed the full 48 weeks of observation, potentially affecting the interpretation of long-term effectiveness and safety.
Variability in visit schedules among centers and potential missing follow-up visits in a real-world setting, which may affect data collection.
Lack of assessment of the causal relationship between serious adverse events and upadacitinib use.
Baseline risk factors may not have been fully identified for all patients.

✨ What It Means For You Upadacitinib offers sustained efficacy in moderate-to-severe atopic dermatitis, even in patients who have failed biologics, with dose flexibility allowing for optimized risk/benefit balance. However, clinicians should exercise caution with upadacitinib in patients over 65, smokers, or those with cardiovascular risk factors, and consider lower doses or alternative therapies when appropriate.

Reference Chiricozzi A, Ortoncelli M, Schena D, Gori N, Ferrucci SM, Babino G, Napolitano M, Fargnoli MC, Stingeni L, Rossi M, Romanelli M, Balestri R, Pellegrino M, Parodi A, Bertoldi AM, Palazzo G, Antonelli F, Pitino A, Tripepi G, Fabbrocini G, Balato A, Marzano AV, Girolomoni G, Ribero S, Peris K. Long-term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis in a Real-world Setting: An Interim Analysis Through 48 Weeks of Observation. American Journal of Clinical Dermatology. 2023;24:953-961. https://doi.org/10.1007/s40257-023-00798-0