Table 4 Systemic treatments for AD targeting PDE, arachidonic acid, and pruritus axes
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 |
|---|---|---|---|---|---|---|
PDE | PDE4 | Apremilast | NCT01393158 (Phase II, pilot study), no placebo arm included. | % Change in the EASI score at 3 months and 6 months. | % Change in the EASI score at 3 months: −8.8% (20 mg apremilast BID). % Change in the EASI score at 6 months: −8.2% (30 mg apremilast BID) [237]. | Completed. |
NCT02087943 (Phase II) | % Change in the EASI score at week 12. | % Change in the EASI score at week 12: −31.57% (apremilast 40 mg), −25.99% (apremilast 30 mg), −10.98% (placebo). Only 40 mg was significant vs. placebo [165]. | Drug development program has been stopped. | |||
NCT00931242 (Phase II, no placebo arm) | IGA success at week 12. | 20% of patients reached the primary endpoint (apremilast 20 mg) [238]. | Completed. | |||
NCT03160248 (Phase II, nummular eczema) | PGA decrease of 2 or more points from baseline or absolute PGA 0/1. | Pending [239] | Completed | |||
AA | CRTH2 | QAW039/Fevipiprant | NCT01785602 (Phase IIa) | % Change in the EASI score at week 12. | EASI in treatment group declined 8.65%, compared to placebo group decline of 6.95% [240]. | Drug development program has been stopped. |
OC000459 | NCT02002208 (Phase IIb) | % Change in the EASI score at week 16. | EASI in treatment group declined 3.8%, compared to placebo group decline of 6.1% [241] | Drug development program has been stopped. | ||
COX and LOX | DS107/DGLA (dihomo gamma linolenic acid) | NCT02211417 (Phase II) | IGA score at week 8. | Pending. | Completed. | |
NCT02864498 (Phase II) | IGA score at week 8. | Pending. | Completed. | |||
NCT03817190 (Phase II) | IGA success and achieving EASI75 at week 16. | A numerically higher proportion of patients in treatment group achieved the primary endpoint, but results were not statistically significant [242]. | Â | |||
Pruritus | IL-31RA | Nemolizumab | NCT01986933 (Phase III) | % Change in visual-analog scale (VAS) score for pruritis at week 12. | VAS% change:−42.8% in nemolizumab vs. −21.4% in placebo group [189] | Completed. |
NCT03985943 (Phase III) | IGA success and achieving EASI75 at week 16. | In progress. | In progress. | |||
IL-31 | BMS-981164 | NCT01614756 (Phase I) | Adverse event and % change in the EASI score from baseline to week 12. | Pending. | Completed. | |
NK1R | VLY-686/tradipitant | NCT02004041 (Phase II) | % Change in the VAS score for pruritis at week 4. | Tradipitant was not superior to placebo in reducing itch intensity in patients with AD [243]. | Completed. | |
NCT02651714 (Phase II) | % Change in the VAS score for pruritus at week 8. | Primary endpoint: 44.2% in tradipitant vs. 30.6% in placebo; p = 0.019) [244]. | Completed. | |||
NCT03568331 (EPIONE, Phase III) | Reduction in the I-NRS score at week 8. | No significant differences compared to placebo. Significant differences in participants with mild AD (IGA score of 1 or 2 at baseline) [194]. | Completed. | |||
NCT04140695 (EPIONE2, Phase III) | Reduction in the WI-NRS score from baseline to week 8. | Pending. | Completed. | |||
Serlopitant | NCT02975206 (ATOMIK, Phase II) | Change in the WI-NRS score at week 6. | Change in the WI-NRS score was not significantly different between groups: −2.25 (serlopitant 5 mg), −2.32 (serlopitant 1 mg), −2.01 (placebo) [245]. | Completed. | ||
H4R | ZPL-3893787/ Adriforant | NCT02424253 (Phase II) | Change in the I-NRS score at week 8. | Change in I-NRS was not significantly different between groups: −3.03 (ZPL-3893787), −2.66 (placebo); but change in EASI was significant (−50% in ZPL-3893787 vs. −27% in placebo) [193]. | Completed. | |
OPRK1 | Difelikefalin | NCT04018027 (Phase II) | Change in the I-NRS score at week 12. | Primary endpoint was met in subset of participants with mild AD (BSA < 10) [195]. | Completed, phase III programmed. |
