Upadacitinib in adolescents, adults
The new analysis looked at up to 4 years of upadacitinib treatment in almost 2,700 adolescents and adults– and over 6,200 patient-years – using integrated data from three ongoing pivotal phase 3 studies: Measure Up 1, Measure Up 2, and AD Up. (Of these patients, 539 were adolescents, Dr. Bunick said after the meeting.)
In the Measure Up studies, patients were randomized 1:1:1 to receive a 15-mg dose, a 30-mg dose, or placebo once daily. In AD Up, patients in each arm received concomitant topical corticosteroids. At week 16, patients receiving the drug continued their assigned treatment during the ongoing blinded extension period, and those receiving placebo were rerandomized to upadacitinib 15 mg or 30 mg.
The exposure-adjusted event rates for any adverse event leading to discontinuation were 4.1/100 patient-years and 4.7/100 patient-years in patients receiving 15 mg and 30 mg, respectively, and the rates of any serious adverse event were 6.5/100 patient-years and 7.5/100 patient-years, Dr. Bunick reported. Three deaths occurred in the 30-mg group; all deaths were related to COVID infection and occurred in adults with cardiovascular risk factors.
Incidence rates of adverse events of special interest were similar to those in a previous 1-year analysis. The rate of serious infections per 100 patient years, for instance, was 2.3 and 2.8 in the 15-mg and 30-mg groups, respectively, compared with 2.2 and 2.8 in the 1-year analysis.
The rate of opportunistic infections, including eczema herpeticum (and excluding TB and herpes zoster), saw a slight bump in the new analysis to 2.4/100 patient-years with the 30-mg dose. Other event rates, across both dosages and durations, were less than 0.1/100 patient-years for active TB; 0.3-0.4/100 patient-years for NMSC, and 0.1/100 patient-years or below for other malignancies, MACE, and VTE. Herpes zoster had the highest event rate in both the 1- and 4-year analyses of between 3.1/100 patient-years and 5.8/100 patient-years, Dr. Bunick reported.
The adverse event rates for adolescents and adults “show consistency and are very low,” Dr. Bunick said. At 4 years, no new safety risks were identified.
‘The more data ... the better’
Data on the safety of new medications in children and adolescents is always important, and with systemic JAK inhibitors in particular, “the more data we can accumulate in [younger] patients with AD ... the better,” said Robert Sidbury, MD, MPH, professor in the department of pediatrics at the University of Washington, Seattle, and chief of the division of dermatology at Seattle Children’s Hospital, who was asked to comment on the two studies.
Dr. Robert Sidbury
Dermatologists have taken comfort in the fact that the “daunting” boxed warning on JAK inhibitors “was generated in a very different population than we generally propose to treat, certainly when talking about children and adolescents,” said Dr. Sidbury, who was not involved in either of the new safety analyses.
The JAK inhibitor boxed warning “reflects a study of tofacitinib – a different JAK inhibitor with arguably more risk of adverse effects – in adults over the age of 50 with rheumatoid arthritis and multiple risk factors for comorbidities included in the boxed warning,” he said.
“This allows dermatologists to reasonably conclude that the boxed warning – while critical to discuss and consider in every patient – is likely less concerning than might otherwise by implied.”
With more patient experience, “the more our assessment of risk, and of the ‘legitimacy’ of the boxed warning in our patient population, becomes evidence-based as opposed to extrapolation,” Dr. Sidbury said.
The two studies reported, he said, “detail an experience that is not adverse effect free –I have yet to find that medication – but is a reasonable profile considering the robust efficacy results they accompany.”
The abrocitinib safety analysis was sponsored by Pfizer. Regarding the study of upadacitinib, AbbVie contributed to the design of the safety analysis and participated in data collection. No honoria or payments were made to the authors, according to the study abstract. Dr. Eichenfield is a consultant/advisory board member for Pfizer and other companies, and has served on the speakers bureau/received honoria for Pfizer and other companies. Dr. Bunick is a consultant for AbbVie and other companies, and has served as an speaker/received honoraria or served as an investigator for several companies. Dr. Sidbury disclosed being a consultant/advisory board member for Lilly and Leo and serving on the speakers bureau/honoraria for Beiersdorf. All reported receiving grant/research support from various companies.