After four weeks on a daily 15- or 30-mg dose of the oral Janus kinase (JAK) 1 inhibitor, most patients with moderate to severe symptoms had 90% to 100% disease clearance, researchers report in The Lancet. Itch responded even more quickly, abating within days of starting the treatment.
"This is an important drug with a remarkable and quick effect," said Dr. Emma Guttman-Yassky, a Waldman Professor and System Chair of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City. "It was not only effective at the higher dose, but the 15 mg dose was better than anything else we have."
"And it's an oral medication so it's a good option for patients who are afraid of needles," Dr. Guttman-Yassky said. "That gives patients the opportunity to stop and restart the drugs as they wish."
It's possible that for some patients the drug might not need to be taken every day, but instead be used only to treat flares, Dr. Guttman-Yassky said.
The new study describes results from two international multicenter, randomized, double-blind, placebo-controlled trials done in a clinical setting: Measure Up 1, which ran from August 13, 2018 to December 23, 2019, and Measure Up 2, which ran between July 27, 2018 and January 17, 2020. The Measure Up 1 trial enrolled 847 patients from 151 clinical centers in 24 countries while the Measure Up 2 trial enrolled 836 patients at 154 clinical centers in 23 countries. Both included adolescents and adults.
The two trials had a 35-day screening period, a 16-week double-blind treatment period, a blinded extension period up to week 260 and a 30-day follow-up visit. In both trials, participants were randomly assigned 1:1:1 to receive 15 mg of the medication, 30 mg of the medication or a placebo once a day. A total of 128 participants discontinued treatment, with fewer of those on the lower dose dropping out compared to those taking the higher dose.
Co-primary endpoints of the trials were the proportion of patients who had achieved at least a 75% improvement in the Eczema Area and Severity Index score from baseline and the proportion of patients who had achieved a validated Investigator's Global Assessment for Atopic Dermatitis of 0 (clear) or 1 (almost clear) at week 16.
At week 16, the co-primary endpoints were met in both trials. The proportion of patients who had achieved EASI-75 at week 16 was significantly higher in both the Measure Up 1 and Measure Up 2 trials among those receiving upadacitinib 15 mg (70% and 60%, respectively) and upadacitinib 30 mg (80% and 73%) than in the placebo group (16% and 13%).
The proportion of patients who achieved a vIGA-AD response at week 16 was also significantly higher in both trials among patients receiving upadacitinib 15 mg (48% and 39%) and upadacitinib 30 mg (62% and 52%) as compared to the placebo group (8% and 5%).
"This is really exciting," said Dr. Maria Wei, a professor of dermatology at the University of California, San Francisco, who wasn't involved in the study. "It's a great report. I think it's the beginning of many new drugs to come and precision medicine for rashes. Atopic dermatitis, which sometimes can be really life-impacting, can leave people unable to sleep, unable to go to work. It's really very uncomfortable and unsightly in their minds."
In patients with atopic dermatitis the immune system overreacts to allergens and irritants and in some, there's an inherited genetic variant that leaves the skin a less effective barrier, which allows small molecules to pass into it, resulting in a cascading immune response that produces symptoms such as rash, itch and irritation, Dr. Wei said. "So, these targeted medications are aimed at blocking that cascade," she added.
Physicians will have to be cautious with upadacitinib, as they should be with any new drug, said Dr. Sonal Choudhary, an assistant professor of dermatology and dermatopathology at the University of Pittsburgh Medical School and the department of dermatology at UPMC, who also wasn't involved in the study. Studies are needed to see what happens if JAK1 is inhibited long term, Dr. Choudhary said. Future studies should also look at the new medication head to head with other drugs designed to treat atopic dermatitis, she added.
What is really needed is a way of bioprofiling patients so it will be clear ahead of time "which pathway went haywire and which drug to choose," Dr. Choudhary said.
SOURCE: https://bit.ly/3454aOD and https://bit.ly/3fECLbt The Lancet, online May 20, 2021.
By Linda Carroll
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