Table 3.
Primary and major secondary endpoints of the most important trials for the drugs mentioned in Section 2, Section 3, Section 4, Section 5 and Section 6.
| Drug | Primary End-Point | Other End-Points |
|---|---|---|
| Delgocitinib | JapicCTI-173554: Mean percent change in mEASI at week 4: −44.3% in the drug group vs. 1.7% for vehicle. (p < 0.001). JapicCTI-173555: Safety: AEs in 69% of patients. 15.4% considered treatment-related. 1.4% considered serious (Kaposi’s varicelliform eruption) |
JapicCTI-173554: mEASI-50 at week 4: 51.9% for drug vs. 11.5% for vehicle (p < 0.001). mEASI-75 at week 4: 26.4% vs. 5.8% respectively (p < 0.01). IGA response rates at week 4: p = 0.32 for overall score, p < 0.05 for face/neck score. NRS: lower in drug group. All results maintained at week 24. JapicCTI-173555: mEASI-50 at week 4, 24, 52: 31.5%, 42.3% and 51.9%. mEASI-75 at week 4, 24, 52: 10.9%, 22.7% and 27.5% IGA and NRS: improved at weeks 4, 24 and 52 |
| Ruxolitinib | IGA 0–1 at week 8: 53.8%(TRuE-AD1) and 51.3% (TRuE-AD2) in the 1.5% cream groups vs. 15.1% and 7.6% for vehicle (p < 0.0001) | EASI-75 at week 8: 62.1% and 61.8% in the 1.5% cream groups vs. 24.6% and 14.4% for vehicle (p < 0.0001). EASI90 at week 8: (p < 0.0001) vs. vehicle. Reduction in NRS: (p < 0.05) vs. vehicle |
| Tofacitinib | EASI score change at week 4: 81.7% vs. 29.9% for vehicle. | EASI 50, 75 and 90: Significantly higher for drug vs. vehicle (p < 0.05) at weeks 2 and 4. Change in BSA: −76% for drug vs. −31% for vehicle, significantly greater (p < 0.001) at week 4. ISI scores: significantly greater for drug vs. vehicle at weeks 2 and 4 (p < 0.001). |
| Brepocitinib | EASI score change at week 6: 70.1%, 67.9%, and 75%, for the 1%, 3% q.d and 1% b.i.d groups respectively. 44.4% and 47.6% in the q.d and b.i.d vehicle groups. |
IGA score of 0/1 at week 6: 27.8–44.4% of patients on q.d drug vs. 10.8% for q.d vehicle. EASI 90 at week 6: 27.8–41.7% of patients on 0.3%, 1%, and 3% q.d cream, vs. 10.8% for q.d vehicle, 27% of patients on 1% b.i.d cream, vs. 8.3% b.i.d vehicle. Improvement of at least 4 points on the PP-NRS at week 6: 45.2% of patients on 1% cream q.d, 50% on 3% q.d, and 40.7% on 1% b.i.d, vs. 17% for vehicle. |
| ATI-1777 | Reduction in mEASI score at week 4: 74.4% in the drug arm, vs. 41.4% for vehicle | not yet available |
| Ifidancitinib | PGA of near clear with ≥2 grade improvement: 10.5%, 23.5%, 41.2% of patients at weeks 1, 2, and 4. |
Change in EASI: 18%, 35%, 40% at weeks 1, 2, and 4. Percent change in SPA: 35%, 46% and 31% at weeks 1, 2, and 4. |
| Jaktinib | PGA 0/1 or a decrease of ≥2, 7 days after the last dose: not yet available | PGA 0/1 at 8 and 16 weeks: not yet available |
| Ivarmacitinib | Change in EASI at Week 8: not yet available | not yet available |
| Crisaborole | ISGA score 0/1 with ≥2 grade improvement at day 29: 32.8% (AD-301) and 31.4% (AD-302) reduction vs. 25.4% (p = 0.038) and 18% (p < 0.001) for vehicle. |
ISGA score 0/1 at day 29: 51.7% vs. 40.6% (p < 0.005) and 48.5% vs. 29.7% (p < 0.001) respectively. Time to ISGA success: 14.7% for drug vs. 5.4% for vehicle at day 8. Median time to improvement in pruritus: 4 days for drug vs. 9 days for vehicle. Mean change in DLQI at day 29: −5.2 for drug vs. −3.5 for vehicle. |
| Difamilast (OPA-15406) | IGA 0–1 with ≥2 grade improvement at week 4: 38.46% of patients in the ointment group vs. 12.64% for vehicle (p < 0.0001) | EASI 50, 75, 90 at week 4: 58.24%, 42.86% and 24.73 of patients in drug group vs. 25.82%, 13.19% and 5.49% for vehicle. Mean percent change in EASI score at week 1: −32.6% vs. −10.4% for drug and vehicle respectively (p < 0.0001). POEM, affected BSA, pruritus VRS, Skindex-16: all significantly improved vs. vehicle (p < 0.0001) at week 4 |
| Lotamilast (E6005, RVT-501) | Long-term safety and tolerance: Neither death nor serious TEAEs were encountered in the entire study period. In the randomization phase, the incidence of TEAEs was 50.0% in the drug group vs. 38.5% for vehicle group. The incidence of TEAEs leading to study withdrawal was 9.6% in the drug group and 15.4% for vehicle group. | Scores reduction at week 12: significantly reduced: EASI, p = 0.030; SCORAD-objective, p < 0.001; SCORAD-C, p = 0.038) Not significantly reduced: Itch Behavioral Rating Scale, (p = 0.462) |
| Roflumilast | Change in Modified Local SCORAD at day 15: Not significant reduction vs. vehicle (p = 0.276) | Change in PAP at day 15: Significantly reduced (p < 0.013) |
| DRM02 | not yet available | not yet available |
| Hemay808 | not yet available | not yet available |
| PF-07038124 | not yet available | not yet available |
| LEO-39652 | not yet available | not yet available |
| Orismilast (LEO-32731) | not yet available | not yet available |
| Tapinarof | IGA response rates at week 12: 53% (1% b.i.d; p = 0.008), 46% (1% q.d; p = 0.084), 37% (0.5% b.i.d; p = 0.240), and 34% (0.5% q.d; p = 0.535) vs. 24% (vehicle b.i.d) and 28% (vehicle q.d). |
EASI75 at week 12: significantly higher in the tapinarof groups, except the 0.5% q.d, vs. vehicle groups. EASI90 at week 12: significantly higher in the tapinarof groups, except the 0.5% b.i.d, vs. vehicle groups. Mean percent change in EASI at week 12: significantly higher in all tapinarof groups vs. vehicle groups. Mean percent change in BSA at week 12: significantly greater in the tapinarof groups, except the 0.5% b.i.d, vs. vehicle groups. |
| Asivatrep | IGA score of 0 or 1 at week 8: 36.0% in the drug group vs. 12.8% for vehicle. | Improvement ≥2 points on IGA score at week 8: 20.3% for drug vs. 7.7% for vehicle. EASI reduction at week 8: 44.3% vs. 21.4% respectively. EASI-50, 75, and 90 at week 8: 50.3%, 23.5%, and 9.8% of patients on drug vs. 28.2%, 11.5%, and 2.6% on vehicle. Statistical significance achieved in all secondary end-points, as also in pruritus and sleep disturbance reduction. |
| R.mucosa | 50% improvement in SCORAD: 66.7% of patients | 75% improvement in SCORAD: 40% of patients. Subjective pruritus: significantly decreased. |
| FB-401 | EASI50: 58% in drug arm vs. 60% in placebo arm | - |
| ShA9 | Safety through day 8 compared to vehicle: Significantly fewer AEs in participants treated with ShA9 (p = 0.044) | EASI and SCORAD: no significant difference Decrease in S. aureus and increased ShA9 DNA: endpoints met |
| Nitrosomonas eutropha | Not yet available, positive results in pruritus and AD appearance reported in press release | - |
| Omiganan gel | S.aureus reduction at day 28: Statistically significant in the omiganan 1% (p = 0.03) and 2.5% (p = 0.01) vs. vehicle. | Clinical improvement evaluated by EASI, SCORAD, IGA, POEM, DLQI and NRS: no improvement |
| ATx201 | Safety: safe and well tolerated | Expression of biomarkers related to skin-barrier function: Significantly increased (p < 0.05). Histological responders: 51.7% of those receiving 2% cream vs. 31.0% for vehicle. |
ISI: Itch Severity Item, PP-NRS: Peak Pruritus Numerical Rating Scale, SPA: Subject’s Pruritus Assessment, DLQI: Dermatology Life Quality Index, VRS: verbal rating scale, PAP: Participants’ Assessment of Pruritus.