Efficacy of Upadacitinib vs Dupilumab for Atopic Dermatitis

The efficacy and safety of upadacitinib for the treatment of moderate to severe atopic dermatitis (AD) found support in study data published in JAMA Dermatology. In a randomized controlled trial which used dupilumab as a comparator agent, upadacitinib demonstrated superior efficacy in symptom reduction. No new safety signals were observed.

The Heads Up trial was a 24-week, randomized, double-blind, active-controlled clinical trial which compared the efficacy and safety of upadacitinib with dupilumab for the treatment of AD. The trial enrolled adults with moderate to severe AD from 129 clinical centers around the world. The randomized treatment phase took place from February 21, 2019 to December 9, 2020. Patients were randomly assigned 1:1 to receive 30 mg of upadacitinib once daily or 300 mg of dupilumab every 2 weeks. Upadacitinib was administered as an extended-release oral tablet; dupilumab was given as a subcutaneous injection. To maintain blinding, all treatment courses were accompanied by a placebo version of the opposite drug.

The primary efficacy endpoint was 75% improvement in Eczema Area and Severity Index at week 16 (EASI75). Secondary endpoints included 90% and 100% improvement on EASI and reduction from baseline in Worst Pruritis Numerical Rating Scale (NRS), which captured the mean intensity of AD-related itch. Safety was assessed as treatment-emergent adverse events occurring in patients who received 1 or more dose of either drug.

A total of 348 patients were randomly assigned to the upadacitinib arm and 344 to the dupilumab arm. Demographic characteristics were comparable in study arms; mean age was 36.6 ± 14.6 years in the upadacitinib group and 36.9 ± 14.1 years in the dupilumab group. Just over half of participants in each group were men. At week 16, 71.0% of the upadacitinib arm and 61.1% of the dupilumab arm achieved EASI75 (P =.006). All secondary endpoints supported the superior efficacy of upadacitinib. A significantly greater percentage of patients in the upadacitinib group achieved EASI100 at week 16 compared to the dupilumab group (27.9% vs 7.6%; P <.001). Mean reduction in Worst Pruritus NRS was greater with upadacitinib as early as week 1 (31.4% vs 8.8%; P <.001), and more patients receiving upadacitinib achieved EASI75 as early as week 2 (43.7% vs 7.6%; P <.001), suggesting earlier improvement with upadacitinib.

No new safety signals for upadacitinib were observed, although treatment-emergent adverse events occurred in a greater percentage of the upadacitinib group compared with the dupilumab group (71.6% vs 62.8%). One death was reported in the upadacitinib group: a 40-year-old patient who developed influenza-associated bronchopneumonia. The most frequently reported adverse event in the upadacitinib group was acne (15.8%). Rates of serious infection (1.1% vs 0.6%), eczema herpeticum (0.3% vs 0%), and herpes zoster (2.0% vs 0.9%) were numerically higher in the upadacitinib group, though the differences were not statistically significant. Conjunctivitis and injection-site reactions were more common in the dupilumab arm.

Results from this study demonstrate the superiority of upadacitinib to dupilumab for the treatment of moderate to severe AD in adults, the researchers believe.

The primary study limitation is the short study period: efficacy endpoints were evaluated after just 16 weeks of treatment. Longer-term data collection is ongoing in an open-label iteration of the study. In addition, the effects of polytherapy were not explored; concomitant use of topical agents, such as corticosteroids, was not captured.

“Upadacitinib achieved higher levels of skin clearance and itch relief with a more rapid onset of action vs dupilumab,” investigators wrote. “Upadacitinib is an effective treatment option for patients with moderate-to-severe AD and may help inform future treatment decisions,”

Disclosure: This research was supported by AbbVie. Please see the original reference for a full list of disclosures

Reference

Blauvelt A, Teixeira HD, Simpson EL, et al. Efficacy and safety of upadacitinib vs dupilumab in adults with moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. Published online August 4, 2021. doi:10.1001/jamadermatol.2021.3023