Upadacitinib Sustains AD Control for 140 Weeks

Systemic treatment of moderate to severe atopic dermatitis (AD) has advanced significantly in recent years, with both JAK inhibitors and biologics now established in clinical practice.¹ While short-term and 1-year outcomes with upadacitinib have been well characterized, there has been limited information on how patients fare with prolonged therapy. An interim analysis from 3 ongoing phase 3 randomized controlled trials, Measure Up 1, Measure Up 2, and AD Up, now provides data through 140 weeks of treatment, representing one of the longest datasets available for an oral advanced systemic therapy in AD.²

The trials enrolled 2,782 adolescents and adults aged 12 to 75 years with moderate to severe AD who were candidates for systemic therapy. Patients were randomized to once-daily upadacitinib 15 mg, upadacitinib 30 mg, or placebo. Those in the placebo groups were rerandomized to active treatment at week 16. Measure Up 1 and Measure Up 2 evaluated monotherapy, while AD Up required concomitant topical corticosteroids (TCS) through week 52, after which topical therapy was optional. Efficacy endpoints included EASI-75/90/100, vIGA-AD 0/1, and itch response using the Worst Pruritus Numerical Rating Scale (WP-NRS). Safety was assessed through week 140.

Efficacy outcomes demonstrated durable responses across all trials. At week 140, between 81.5% and 88.8% of patients on the 15 mg dose and around 90% on the 30 mg dose achieved EASI-75. For the more stringent EASI-90 target, response rates ranged from 60% to over 77% across the 2 dose groups. Clinician-assessed clearance, defined as vIGA-AD 0/1, was achieved by approximately half of patients on the lower dose and over 60% on the higher dose. Improvements in itch were similarly durable: at week 140, 61% to 68% of patients on 15 mg and 71% to 75% on 30 mg reported at least a 4-point reduction in WP-NRS, with many achieving scores of 0 or 1, reflecting minimal or absent pruritus. Notably, most patients who responded at week 16 maintained response through nearly three years, while a substantial proportion of early nonresponders ultimately achieved EASI-75 by week 140.

Patterns of topical therapy use differed by study design. In the monotherapy trials, approximately 60% of patients never required additional topical therapy throughout the study. By contrast, in the AD Up trial, where TCS use was mandated through the first year, 40 to 56% of patients remained on topical agents long term. This suggests that initial treatment regimens may influence ongoing topical utilization, even in the context of systemic disease control.

Safety results were consistent with prior reports and did not reveal new signals. The most common treatment-emergent adverse events included COVID-19, nasopharyngitis, acne, upper respiratory tract infection, AD flares, and creatine phosphokinase elevation. Serious infections remained uncommon, though slightly more frequent at the higher dose. Opportunistic infections, primarily eczema herpeticum, were dose-dependent but rare overall. Rates of herpes zoster and certain laboratory abnormalities, including hepatic enzyme elevations and cytopenias, were higher with the 30 mg dose, though generally nonserious and not treatment-limiting. Importantly, rates of major adverse cardiovascular events, venous thromboembolism, and malignancies were low and in line with background rates in AD populations. Seven deaths were reported, none deemed related to study drug.

For clinicians, these findings highlight the sustained efficacy of upadacitinib, both for skin clearance and pruritus relief, across nearly 3 years of therapy. The data reinforce that continued treatment benefits not only early responders but also patients who do not meet targets in the initial months, as many of these individuals achieved significant response with longer exposure. The safety profile was consistent with prior JAK inhibitor experience, with the 30 mg dose associated with incrementally higher risks of herpes zoster and certain laboratory abnormalities.

Overall, researchers found this 140-week analysis strengthens the evidence base for upadacitinib as a long-term therapeutic option for moderate to severe AD. The results support its use as either monotherapy or in combination with topical agents, with dosing decisions individualized based on the balance between efficacy needs and patient-specific risk factors. For clinicians managing chronic AD, these extended data provide reassurance regarding both durability of disease control and the predictability of safety outcomes with upadacitinib.

References

1. Gallagher K, Halperin-Goldstein S, Paller AS. New treatments in atopic dermatitis update. Ann Allergy Asthma Immunol. 2025. doi:10.1016/j.anai.2025.06.020
2. Irvine AD, Prajapati VH, Guttman-Yassky E, et al. Efficacy and safety of upadacitinib in patients with moderate-to-severe atopic dermatitis: Phase 3 randomized clinical trial results through 140 weeks. Am J Clin Dermatol. 2025. doi:10.1007/s40257-025-00975-3