Upadacitinib beats dupilumab in different body regions

Analysing the Heads Up outcomes according to improvement in Eczema Area and Severity Index (EASI) in 4 body regions confirmed the overall superiority of upadacitinib over dupilumab in atopic dermatitis (AD). The results were most significant in the achievement rates of clear or almost clear skin.

The multicentre, phase 3b Heads Up study (NCT03738397) directly compared treatment efficacy and safety of upadacitinib to dupilumab in moderate-to-severe AD [1]. The results were clearly in favour of upadacitinib in the primary and secondary endpoints. To further evaluate these outcomes, Prof. Jacob Thyssen (Bispebjerg Hospital, Denmark) and colleagues assessed the treatment responses of EASI reduction in the Heads Up trial over 24 weeks in the 4 different anatomical regions that form part of the assessment within this score: head and neck, trunk, upper limbs, and lower limbs [2]. Nearly half of the 692 Heads Up participants were women, and the mean age was 36.6 years. Overall baseline characteristics were considered balanced between the 2 study arms [1].

The rates of participants achieving EASI 100, 90, and 75 in the head-and-neck region showed interesting results [2]. “What you can see is a very, very fast onset of action in particular for upadacitinib. After just 1 to 2 weeks there is a significant difference compared with dupilumab,” commented Prof. Thyssen. At week 24, a proportion of 36.0% on upadacitinib achieved EASI 100 compared with 28.5% receiving dupilumab (P<0.05). Furthermore, the rate of those reaching EASI 90 on upadacitinib was significantly superior to dupilumab (47.0% vs 38.1%; P<0.05). Although upadacitinib also led to significantly greater rates of EASI 75 until week 20, at week 24 the difference between the 2 groups seized to be significantly different. Outcomes for the trunk region followed a similar pattern.

“Upadacitinib is more potent than dupilumab when we go for the very ambitious scores, i.e. EASI 100 and EASI 90, whereas for EASI 75 we see a very dramatic difference in the beginning, and then it seems to level out a bit after 24 weeks of observation,” was Prof. Thyssen’s evaluation of the results. Efficacy parameters of the same magnitudes were observed in the regions of the upper and lower limbs. For example, EASI 100 rates in the upper limb region were 38.8% in the upadacitinib group versus 25.9% in the dupilumab group, respectively (P<0.001). In the lower limbs, these percentages for EASI 100 were 47.7% on upadacitinib and 36.1% on dupilumab (P<0.01).

Prof. Thyssen stated that both drugs were generally safe and well-tolerated and that the results were very much comparable with the safety reports from previous trials.

“Deeper responses with stringent clearance measures such as EASI 90 or EASI 100 are indeed attainable and are clinically meaningful,” Prof. Thyssen highlighted. His summary stressed that greater proportions of patients with moderate-to-severe AD treated with upadacitinib compared with dupilumab achieved improvements in skin clearance, with differences seen in EASI 100 by week 4 and EASI 90 by week 2, both sustained until week 24, as well as EASI 75 by week 1, sustained through week 16.

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   1. Blauvelt A, et al. JAMA Dermatol. 2021;157(9):1047–1055.
   2. Thyssen JP. Efficacy and safety of upadacitinib vs dupilumab treatment for moderate to severe atopic dermatitis in four body regions - Analysis from the heads up study. FC01.03, EADV Congress 2021, 29 Sept–2 Oct.

 

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Posted on 18 November 202118 November 2021