Upadacitinib was well-tolerated and associated with high levels of skin clearance and itch improvement through 40 weeks with no new safety risks in patients with moderate to severe atopic dermatitis. Skin and itch outcomes were improved with upadacitinib regardless of patients’ prior responses to dupilumab. These findings were published in the Journal of the American Academy of Dermatology.
Researchers reported results of a 16-week interim analysis of a 52-week open-label extension of the phase 3 randomized controlled Heads Up trial. Patients treated with once-daily oral upadacitinib at 30 mg until week 24 in Heads Up continued to receive the same dose, and those who received subcutaneous dupilumab at 300 mg every other week until week 22 in Heads Up switched to once-daily oral upadacitinib at 30 mg. The primary study endpoint was safety. Safety data were reported as exposure-adjusted event (E) rate per 100 patient-years (PY).
A total of 635 patients completed week 24 of Heads Up, and 484 were included in the open-label extension. Treatment with upadacitinib was continued in 239 patients and 245 switched from dupilumab to upadacitinib. The median duration of exposure to upadacitinib at data cutoff was 366 days (range, 172-554) for patients who continued on upadacitinib and 198 days (range, 56-375) for patients who switched from dupilumab to upadacitinib.
The safety profile to week 40 for upadacitinib was consistent with that reported in other phase 3 clinical trials in patients with atopic dermatitis. Adverse events in patients who switched from dupilumab to upadacitinib were comparable to those occurring in patients who had received continuous treatment with upadacitinib.
Researchers reported results of a 16-week interim analysis of a 52-week open-label extension of the phase 3 randomized controlled Heads Up trial. Patients treated with once-daily oral upadacitinib at 30 mg until week 24 in Heads Up continued to receive the same dose, and those who received subcutaneous dupilumab at 300 mg every other week until week 22 in Heads Up switched to once-daily oral upadacitinib at 30 mg. The primary study endpoint was safety. Safety data were reported as exposure-adjusted event (E) rate per 100 patient-years (PY).
A total of 635 patients completed week 24 of Heads Up, and 484 were included in the open-label extension. Treatment with upadacitinib was continued in 239 patients and 245 switched from dupilumab to upadacitinib. The median duration of exposure to upadacitinib at data cutoff was 366 days (range, 172-554) for patients who continued on upadacitinib and 198 days (range, 56-375) for patients who switched from dupilumab to upadacitinib.
The safety profile to week 40 for upadacitinib was consistent with that reported in other phase 3 clinical trials in patients with atopic dermatitis. Adverse events in patients who switched from dupilumab to upadacitinib were comparable to those occurring in patients who had received continuous treatment with upadacitinib.
For patients who received at least 1 dose of upadacitinib, the incidence rate of serious adverse events and adverse events leading to study drug discontinuation was 5.2 E/100 PY and 4.4 E/100 PY, respectively. The most frequently occurring adverse events were acne (30.5 E/100 PY) and worsening atopic dermatitis (20.8 E/100 PY).
Patients who received continuous upadacitinib had improvement in their mean Eczema Area and Severity Index (EASI) score, from 30.5 at baseline to 2.6 at week 24 of Heads Up. At week 40 (week 16 of open-label extension), the improvements continued at a level similar to that at week 24 of Heads Up, with a mean EASI score of 2.7 (range, 0-40.2). In addition, 91% of patients who received continuous treatment with upadacitinib had an EASI score of 7 or lower, and 73.6% achieved EASI90.
Patients’ mean EASI improved with dupilumab from 28.8 to 3.29 at week 24 of Heads Up. After switching to upadacitinib, patients’ mean EASI improved to 1.09 at week 16 of the open-label extension, and 98% of patients who switched from dupilumab to upadacitinib had an EASI score of 7 or lower at week 16. The percentage of patients with EASI75 increased within 4 weeks of switching to upadacitinib, from 85.7% to 96.2%, and was 96.6% at week 16 of the open-label extension.
Patients with a previous response to dupilumab had incremental improvements in EASI and Worst Pruritus Numerical Rating Scale (WP-NRS) scores within 4 weeks of initiating upadacitinib. Among patients who achieved EASI75 but not EASI90 with dupilumab, 84.1% achieved EASI90 after 16 weeks of upadacitinib.
Among patients who had an inadequate response to previous treatment with dupilumab, 92.8% achieved EASI75 at week 16 with upadacitinib.
Limitations of this study include its open-label design, short washout period for dupilumab, exploratory efficacy endpoints, and short follow-up duration of upadacitinib in patients who switched from dupilumab.
“[U]padacitinib provides greater efficacy compared with dupilumab, has a favorable benefit-risk profile, and patients regardless of prior dupilumab response status experienced improved outcomes when switched to upadacitinib,” the researchers concluded.
References:
Blauvelt A, Ladizinski B, Prajapati VH, et al. Efficacy and safety of switching from dupilumab to upadacitinib versus continuous upadacitinib in moderate-to-severe atopic dermatitis: results from an open-label extension of the phase 3, randomized, controlled trial (Heads Up). J Am Acad Dermatol. Published online May 23, 2023. doi:10.1016/j.jaad.2023.05.033
