Oral Medication Shows Strong Promise for Moderate to Severe Atopic Dermatitis in Mount Sinai-led Study
Rapid itch improvements achieved in patients taking systemic oral medication in phase 3 trials
An oral medication called upadacitinib yielded rapid and significant improvements in patients with moderate to severe atopic dermatitis (AD), also known as eczema, in phase 3 clinical trials, Mount Sinai researchers reported today in The Lancet online.
Patients who received upadacitinib, a Janus kinase inhibitor 1 (JAK1 inhibitor), showed impressive reductions in all clinical disease measures, as well as in all itch-related outcomes. “The results of these trials (Measure Up 1 and Measure Up 2) were so incredible that by week 16, most patients with moderate to severe atopic dermatitis either had a 90 percent disease clearance, or even 100 percent disease clearance,” said Emma Guttman-Yassky, MD, PhD, Waldman Professor and System Chair of the Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, and first author of the paper.
“We achieved extremely high clearance rates that are bringing us closer to the amazing clearance rates that we see in psoriasis,” said Dr. Guttman-Yassky. “Also, the itch improvements already started to be significant within days from the beginning of the trials, and the maximum clinical efficacy was obtained early, at week 4, and maintained to week 16.” She also noted that upadacitinib was well tolerated by patients in the doses of the drug—15 mg and 30mg—and no important safety risks were observed.
JAK inhibitors are a type of medication that function by inhibiting the activity of one or more of the Janus kinase family of enzymes (JAK1, JAK2, JAK3, TYK2), thereby interfering with the JAK-STAT signaling pathway. These JAK inhibitors have therapeutic application in the treatment of cancer, and inflammatory disease such as rheumatoid arthritis, and potentially other skin conditions, including atopic dermatitis.
In this study, the JAK1 inhibitor upadacitinib blockades multiple cytokine signaling pathways, parts of the immune system that malfunction in atopic dermatitis. Blocking these pathways helps achieve greater response and higher thresholds in skin improvement in patients who have moderate to severe atopic dermatitis.
Atopic dermatitis is an inflammatory, extremely itchy skin disorder that affects more than 31 million adults in the United States, including 10 to 20 percent of children. Patients who have moderate to severe atopic dermatitis experience increased itch, skin pain, and sleep disruption; greater comorbidity risk (for asthma, hay fever, allergies, depression, and suicidal ideation, for example); and often report diminished self-esteem, substandard performance at school/work, and overall impaired health-related quality of life compared with the general public. While the condition may occur at any age, it typically starts in childhood, with changing severity over the years.
“The results achieved with this study were very impressive and provided robust efficacy,” said Dr. Guttman-Yassky. “Patients were able to start and restart the oral medication at any time, allowing for flexibility, which cannot be achieved with biologics. And, biologics, which are injectable agents that target specific lymphocytes that are "misbehaving" or are upregulated in atopic dermatitis, do not suppress the entire immune system as other immunosuppressants tend to do.”
While biologics have been very successful for treating patients with atopic dermatitis for whom topical treatments have not worked or are not advised, Dr. Guttman-Yassky explained that they cannot be stopped and restarted at will because of a potential to create anti-drug antibodies, which will shorten the half-life of the drug.
Additionally, Dr. Guttman-Yassky noted that the study also provided the opportunity for adolescents and adult patients who fear injections the option of taking an oral systemic medication for their disease and is an alternative for those suffering from moderate to severe atopic dermatitis.
To watch a video about the study and Dr. Guttman-Yassky’s research click here.
Measure Up 1 and Measure Up 2 trials represent the largest global studies of upadacitinib monotherapy in atopic dermatitis to date. The Measure Up 1 study took place between August 13, 2018, and December 23, 2019, and 847 patients were enrolled. The Measure Up 2 study took place between July 27, 2018, and January 17, 2020, and 836 patients were enrolled. The study was funded by AbbVie, Inc.
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Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in 4 out of 10 pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.