Table 5 Topical treatments for AD targeting the JAK-STAT axis and PDE
From: The translational revolution in atopic dermatitis: the paradigm shift from pathogenesis to treatment
Axis | Target | Drug | Clinical trial (NCT number) | Primary endpoint | Results | Status of investigation |
|---|---|---|---|---|---|---|
JAK-STAT | JAK 1/2/3, TYK2 | Delgocitinib ointment | NCT03725722 (Phase II) | % Change in the EASI score at week 8. | EASI improvement was −1.9 vehicle group vs. −5.0 delgocitinib 1 mg/g vs. −4.9 delgocitinib 3 mg/g vs. −5.8 delgocitinib 8 mg/g vs. −7.6 delgocitinib 20 mg/g [246]. | Completed. |
JapicCTI-173554 (Phase III) | % Change in the EASI score at week 24. | EASI change was −44.3% delgocitinib vs. 1.7% placebo [247]. | Approved in Japan. | |||
JAK 1/2 | Ruxolitinib cream | NCT03745638 (TRuE AD1, Phase III), adolescents and adults. | IGA success at week 8. | IGA success was achieved in 15.1% vehicle vs. 50% ruxolitinib 0.75% vs. 53.8% ruxolitinib 1.5% [152]. | FDA approved for the treatment of mild-to-moderate AD in patients aged 12 years and older (September 2021) | |
NCT03745651 (TRuE AD2, Phase III, and open-label long-term extension) adolescents and adults. | IGA success at week 8. | IGA success was achieved in 7.6% vehicle vs. 39% ruxolitinib 0.75% vs. 51.3% ruxolitinib 1.5% [152]. | ||||
JAK 1/3 | ATI-1777 solution | NCT04598269 (Phase II) | % Change in the EASI score at Day 28. | Pending. | Completed. | |
Tofacitinib ointment | NCT02001181 (Phase IIa) | % Change in the EASI score at week 4. | EASI change was −81.7% tofacitinib vs. −29.9% vehicle [153]. | Completed. | ||
Ifidancitinib (ATI-502) solution | NCT03585296 (Phase II), no vehicle group. | Safety and tolerability at week 8. | 0% mortality, 4.55% serious adverse event (cellulitis, n = 1/22), 31.82% other TEAE (N = 7/22) [154]. | Completed. | ||
JAK3, TrkA | SNA-125 | Phase I/II | Safety and tolerability after 14 days. | No serious adverse events reported [248]. | Phase II study was planned for 2019. | |
PDE inhibitors | PDE4 | Crisaborole 2% ointment | NCT02118766 (AD-301, Phase III) participants 2 years and older. | IGA success at Day 29 and safety. | IGA success: 32.8% crisaborole 2% vs. 25.4% vehicle [167]. | FDA approved for mild-to-moderate AD in participants as young as 3 months of age (March 2020). |
NCT02118792 (AD-302, Phase III) participants 2 years and older. | IGA success at Day 29 and safety. | IGA success: 31.4% crisaborole 2% vs. 18% vehicle [167]. | ||||
NCT03645057 (Phase III) children. | Itch and pain at week 12. | Pending. | ||||
NCT04360187 (Phase III); Chinese and Japanese 2 years and older. | % Change in the EASI score at Day 29 and safety. | EASI change was −59.92% crisaborole 2% vs. −42.79% vehicle [249]. | ||||
NCT04040192 (Phase III) children and adults. | Flare free maintenance and safety (week 52) | Pending. | ||||
NCT04498403 (Phase III) Japanese children and adults. | TEAEs at week 12. | TEAEs: 30.0% crisaborole 2% (adults), vs. 36.7% crisaborole 2% (pediatric) [250]. | ||||
Difamilast/ OPA-15406 ointment | NCT03908970 (Phase III) | IGA success at week 4. | IGA success: 38.46% difamilast 1% vs. 12.64% vehicle [251]. | Completed. | ||
NCT03911401 (Phase III), pediatric. | IGA success at week 4. | IGA success: 44.58% difamilast 0.3% vs. 47.06% difamilast 1% vs. 18.07% vehicle [252]. | Completed. | |||
NCT03961529 (Phase III) children and adults. | Safety (number of TEAEs up to week 52). | TEAEs: 72.3% difamilast 1% (adults), vs. 91.0% difamilast 0.3% (pediatric) vs. 83.9% difamilast 1% (pediatric) [253]. | Completed. | |||
Roflumilast/ ARQ-151 cream | NCT01856764 (Phase IIa) | Change in SCORAD at Day 15. | Change in SCORAD was −2.30 roflumilast 0.5% vs. −1.75 vehicle (nonsignificant change), but significant difference was seen in pruritus symptom [254]. | Completed. | ||
NCT00746382 (Phase II) | Improvement in clinical signs and symptoms score, improvement in pruritus severity. | Study withdrawn due to business decisions. No participants were treated. | No participants were treated. | |||
Lotamilast/ RVT-501/ E6005 ointment | NCT03394677 (Phase II) children | IGA, EASI, I-NRS, and BSA scores at Day 28. | Pending. | Completed. | ||
NCT02950922 (Phase II) adolescents and adults. | Safety and tolerance at Day 28. | Pending. | Completed. | |||
NCT01461941 (Phase II) | Change in the EASI score and pruritus at week 12. | Changes in EASI and pruritus were numerically higher in the treatment group compared to placebo group, but not statistically signifcant [255]. | Completed. | |||
DRM02 gel | NCT01993420 (Phase II) | Change in physicians' lesion assessment at week 6. | Pending. | Completed. |
