Upadacitinib has ‘favorable’ benefit-risk profile for atopic dermatitis

Upadacitinib was well tolerated with no new important safety risks among patients with moderate to severe atopic dermatitis treated for approximately 1 year, according to a study published in The Journal of Allergy & Clinical Immunology.

These patients included adolescents aged 12 to 17 years who weighed more than 40 kg, Emma Guttman-Yassky, MD, PhD, Waldman Professor and System Chair of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai, and colleagues wrote.

The researchers compiled data from a phase 2b study and three ongoing phase 3 studies, looking at their 16-week placebo-controlled periods as well as their longer-term results.

The 16-week analysis comprised 2,707 patients, including 343 adolescents, taking either 15 mg (n = 899) or 30 mg (n = 906) of upadacitinib (Rinvoq, AbbVie) or placebo (n = 902) orally each day. Mean durations of exposure included 110 days for the upadacitinib groups and 103 days for the placebo group.

After 16 weeks, patients on placebo could choose to continue with upadacitinib.

The longer-term analysis involved 2,485 patients, including 333 adolescents, who received daily oral upadacitinib doses of 15 mg (n = 1,239) or 30 mg (n = 1,246). Mean durations of exposure included 405 days for the 15 mg group and 415 days for the 30 mg group.

Overall, more patients in the 30 mg vs. 15 mg upadacitinib group experienced treatment-emergent adverse events (311.9 events vs. 274.6 events per 100 patient-years) and discontinuation due to adverse events (5.7 events vs. 4.4 events per 100 patient-years), with comparable rates of serious adverse events 7.1 events vs. 7.7 events per 100 patient-years).

Researchers also noted higher event rates among adults aged 65 years and older, regardless of treatment assignment.

Acne was the most frequently reported treatment-emergent adverse event in the upadacitinib groups, followed by nasopharyngitis, upper respiratory tract infections, headache, increased blood creatine phosphokinase and oral herpes.

Specifically, patients assigned 30 mg dose had higher incidences of acne in the 16-week analysis (15.8% vs. 15 mg: 10% vs. placebo: 2.2%) and all-exposure analysis (21.4% vs. 15 mg: 14.4%). Acne also was reported more frequently among adolescents than the other age groups.

Exposure-adjusted event rates of serious infections were similar between all groups in both analyses, and rates of malignant neoplasms appeared within the expected range for the general population.

None of the patients experienced any adjudicated major adverse cardiovascular events (MACE) or venous thromboembolism events in the 16-week analysis.

In the all-exposure analysis, MACE exposure-adjusted incidence rates included 0.1 per 100 patient-years in the 15 mg group and less than 0.1 per 100 patient-years in the 30 mg group. The three cases of MACE that occurred were nonfatal strokes in patients aged 60 years and older, including two patients who had uncontrolled hypertension and/or cardiovascular disease.

During the all-exposure analysis, one patient in the 15 mg group experienced deep vein thrombosis, and one patient in the 30 mg group had a pulmonary embolism. Both patients had at least one risk factor for thrombosis.

In other outcomes, the 30 mg group had higher exposure-adjusted event rates for anemia than the 15 mg group in both analyses, although grade 3 anemia was uncommon and none of these events were serious or led to treatment discontinuation among adolescents.

The researchers also found an association between small dose-dependent decreases in mean neutrophil count and higher rates of neutropenia in the 30 mg group, with most events occurring within the first 16 weeks of exposure.

Treatment also appeared linked to elevated liver enzyme levels, although no hepatic events were serious, as well as transient and nonserious elevations in creatine phosphokinase levels.

Overall, these results show that event rates at 1 year appear generally consistent with rates reported at shorter follow-up and “support a favorable benefit-risk profile of upadacitinib in the treatment of patients with moderate to severe AD, including adolescents,” the researchers wrote. However, they cautioned that patients should be tested for tuberculosis and that the elderly and those with cardiovascular risk factors in particular should be evaluated before treatment as well.

The researchers further noted that additional studies are necessary to assess the safety of upadacitinib treatment durations longer than a year with further characterizations in real-world settings.