Superior EASI scores after switch from dupilumab to upadacitinib

Adults with moderate-to-severe atopic dermatitis (AD) demonstrated relevant improvements after switching from dupilumab to upadacitinib in an open-label, extension trial of the Heads Up trial. No new safety signals have been reported in the extension trial.

“Upadacitinib is an oral, once-daily Janus kinase (JAK) inhibitor with greater potency for inhibiting JAK1 compared with JAK2, JAK3, and tyrosine kinase (TYK)2. It is approved by the European Commission for the treatment of adults and adolescents with moderate-to-severe AD and is under review by the FDA for this indication,” said Prof. Andrew Blauvelt (Oregon Medical Research Center, OR, USA) [1]. Following the Heads Up trial (NCT03738397), an open-label extension (OLE) study (NCT04195698) evaluated the long-term safety and efficacy of switching from dupilumab to upadacitinib in patients with moderate-to-severe AD. The initial Heads Up trial was a 24-week, head-to-head, phase 3b investigation that demonstrated superiority of upadacitinib over dupilumab not only in the primary but also in all ranked secondary endpoints [2]. After week 24, patients who had been in the upadacitinib 30 mg arm continued their treatment in the extension trial, while subjects in the former dupilumab 300 mg group were switched to 30 mg upadacitinib up to week 52 [1]. Prof. Blauvelt presented the results of the current interim analysis at week 16.

Of a total of 484 participants in the extension study, 245 switched from dupilumab to upadacitinib, the others were continuously treated with upadacitinib. In Heads Up, the mean Eczema Area and Severity Index (EASI) score and body surface area were around 30% and 46%, respectively, while the matching values in the extension trial were about 3% and 6% as patients had already received therapy.

Focusing on the OLE interim results, Prof. Blauvelt stated that those who switched to upadacitinib showed a very clear improvement. The rate of switched participants with EASI 100 increased from 16% in Heads Up to 42.4% in the OLE study, EASI 90 from 66.4% to 87.7%, and EASI 75 from 85.7% to 96.6%, respectively. Furthermore, itch improvement ≥4 on the Worst Pruritus-Numerical Rating Scale also ameliorated markedly.

Treatment-emergent adverse events were assessed through week 40 (at week 16 of the extension study). “We see that the rate of adverse events remained fairly stable over time; they are a little higher in patients who stayed on continuous upadacitinib,” Prof. Blauvelt said. However, he also reported 1 death from tuberculosis in the upadacitinib group. “Looking at the side effects of interest for a JAK inhibitor, you see a fairly consistent profile with what we are used to with upadacitinib and other JAK inhibitors,” he further elaborated.

“We are showing here that switching from dupilumab to upadacitinib results in significant improvements and in higher levels of efficacy than we see with dupilumab alone,” Prof. Blauvelt summarised.

1. 
   
   1. Blauvelt A. Efficacy and safety of switching from dupilumab to upadacitinib in moderate-to-severe atopic dermatitis: Results from an open-label extension trial. D1T01.3B, EADV Congress 2021, 29 Sept–2 Oct.

 

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Posted on 18 November 202118 November 2021