A topical pan-Janus kinase (JAK) inhibitor significantly improved atopic dermatitis (AD) after 8 weeks in a randomized, multidose, vehicle-controlled trial.
Two-thirds of patients treated with the highest dose of delgocitinib cream had at least 75% improvement in the Eczema Area and Severity Index (EASI 75). From 40% to 56% of patients randomized to lower doses of delgocitinib also had EASI 75 responses at 8 weeks. In contrast, 20.8% of patients allocated to a control cream had EASI 75 responses.
Investigator Global Assessment-Atopic Dermatitis (IGA-AD), dermatology-specific quality of life (QoL), itch and other key outcomes also improved significantly as compared with the control group, reported Jonathan Silverberg, MD, of George Washington University in Washington, at the American Academy of Dermatology virtual meeting.
“All of the doses separate clearly from the vehicle early on, already by 1 week, and that separation continues out to week 8,” said Silverberg. “But clearly the highest dose of 20 mg per gram has the greatest efficacy compared to the other doses. We see significant improvements in the EASI 75 response rates across different dosing arms, but the 20-mg formulation really shows the best efficacy across all time points.”
Delgocitinib has broad-spectrum inhibition of JAK-pathway signaling, including JAK1-3 and tyrosine kinase 2. In a proof-of-concept study, topical delgocitinib led to IGA 0/1 responses (clear/nearly clear) in almost half of patients with chronic hand eczema, three times more as compared with patients randomized to a vehicle control group.
Silverberg reported findings from a multicenter, randomized, vehicle-controlled, dose-ranging phase IIb trial involving adults with AD of at least 1-year duration. Eligible patients had 5% to 50% treatable body surface area (BSA) and disease severity ranging from mild to severe (IGA-AD ≥2).
Patients were randomized to vehicle or one of four delgocitinib arms (1 to 20 mg). Key objectives included establishment of the dose-response relationship, safety, health-related QoL, and efficacy of twice-daily delgocitinib versus the cream vehicle. The primary endpoint was the change in EASI score from baseline to week 8.
Data analysis included 251 randomized patients who had a median age of 37. Women accounted for 68% of the study population. Median age at diagnosis was 12, median disease duration of 19 years, median BSA was 10% (range 4.8%-50%), and median baseline EASI of 10.0.
The results showed a decrease in EASI score of 7.6 from baseline to week 8 for the 20-mg delgocitinib arm as compared with 1.9 in the control group (nominal P<0.05). The other delgocitinib groups had dose-associated reductions of 5.8 to 4.9. Baseline EASI scores for the 20- and 8-mg groups had decreased significantly versus the control group by week 1 (P<0.01).
Comparison of the proportion of patients who achieved EASI 75 scores by week also showed a significant advantage (nominal P<0.05) for the delgocitinib groups versus placebo, including a significant difference between the 20-mg dose and the control group at week 1 (P<0.05).
At baseline, 35.9% of the patients had mild AD (IGA-AD 2), 55.8% had moderately severe AD (IGA-AD 3), and 8.4% had severe AD (IGA-AD 4). An IGA-AD response was defined as a decrease in score to 0/1 and at least a two-step improvement from baseline score. The results showed that 48% of the patients in the 20-mg delgocitinib arm met IGA-AD response criteria as compared with 10.4% of the control group (P<0.0001). The other delgocitinib groups had IGA-AD response rates of 18.4-30%, and only the 1-mg dose of the topical JAK inhibitor failed to outperform the control arm, Silverberg reported.
Comparison of QoL scores also showed a significant advantage for the delgocitinib arms. The study population had a baseline mean Dermatology Life Quality Index (DLQI) score of 10.8, which declined by 8.1 points in the 20-mg delgocitinib arm by week 8 as compared with a decrease of 3.7 points in the control group (P<0.0001). The other delgocitinib arms had decreases of 6.1 to 6.3 points at 8 weeks (nominal P<0.05).
The study had a baseline mean itch score of 6.1, which decreased by 4.6 points in the 20-mg delgocitinib group by week 8, 2.8-3.0 points in the other delgocitinib arms, and 1.0 in the control group (nominal P<0.05). Daily itch score declined significantly versus the control group by day 2 in all but the lowest dose of delgocitinib (nominal P<0.05).
Overall, delgocitinib exhibited a safety profile comparable to that of the control group, said Silverberg. Treatment-emergent adverse events occurred in fewer patients in each of the delgocitinib arms as compared with the control group.
Last Updated April 27, 2021
The study was supported by LEO Pharma.
Silverberg disclosed relevant relationships with LEO Pharma, AbbVie, AnaptysBio, Asana BioSciences, Galderma, GlaxoSmithKline, Glenmark Generics, Kiniksa, Lilly, MedImmune, Menlo Therapeutics, Pfizer, PuriCore, Regeneron, and Sanofi.