"Other than efficacy, there are several other differences in these two medications," Dr. Andrew Blauvelt of Oregon Medical Research Center in Portland told Reuters Health by email. "Some patients will have a preference for how their medication is administered; dupilumab is administered as a subcutaneous shot every two weeks, whereas upadacitinib is given as a pill once daily."
"Regarding safety concerns, upadacitinib has boxed warnings for infection, cancer, and blood clots, and will require routine blood test monitoring, whereas dupilumab does not have these warnings and does not require blood test monitoring," he noted. "However, conjunctivitis is a fairly common side effect with dupilumab, but does not occur with upadacitinib use. So, drug selection for a given patient will require discussing the various pros and cons of each drug with each patient."
As reported in JAMA Dermatology, Dr. Blauvelt and colleagues randomized 692 adults (mean age, 36; about 55% men) with moderate-to-severe to oral upadacitinib, 30 mg once daily, or subcutaneous dupilumab, 300 mg every other week for 16 weeks.
The primary end point was 75% improvement in the Eczema Area and Severity Index (EASI75) at week 16.
The primary endpoint was achieved in 71% of patients receiving upadacitinib and 61.1% of those taking dupilumab. Various secondary endpoints also favored upadacitinib versus dupilumab, including improvement in Worst Pruritus NRS by week 1 (mean, 31.4% vs. 8.8%); achievement of EASI75 by week 2 (43.7% vs. 17.4%); and achievement of EASI100 at week 16 (27.9% vs. 7.6%).
Rates of serious infection, eczema herpeticum, herpes zoster, and laboratory-related adverse events were higher for those who received upadacitinib; by contrast, rates of conjunctivitis and injection-site reactions were higher for patients who received dupilumab.
Dr. Kimberly Morel, Associate Professor of Dermatology and Pediatrics at Columbia University Medical Center in New York City, told Reuters Health in an email that while she is "excited" about the prospect of an oral treatment for atopic dermatitis, "The main concerns are related to the immunosuppressive effects of the JAK inhibitor upadacitinib."
Like Dr. Blauvelt, she noted, "Patients do require warnings about the increased risks associated with this medication, especially infection, malignancy and blood clots."
"Pretreatment assessments for infection as well as baseline blood work and interval blood work monitoring for anemia, liver and lipids are required for upadacitinib," she noted. "There is no pretreatment or laboratory monitoring with dupilumab, so although it does require a subcutaneous injection every 2-4 weeks, no blood draws are required."
"Dupilumab's main infection warning is related to difficulty fighting off helminthic infection," she said. "Patients may feel more comfortable with the safety profile of dupilumab over upadacitinib."
Further, she added, "We don't know the long-term safety of either medication and so ongoing studies will be needed to determine these outcomes."
The study was funded by AbbVie. Five coauthors are employees and Dr. Blauvelt and a number of other coauthors received funding from the company.
SOURCE: https://bit.ly/3jKGKp0 JAMA Dermatology, online August 4, 2021
By Marilynn Larkin
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