Table 1.
Results From Phase III Clinical Trials of Oral JAK Inhibitors Used for AD Patients: Baricitinib, Upadacitinib and Abrocitinib.
| Drug name | Main JAK inhibition | Trial Name | Patients, n. | Study duration | (Co)Primary Endpoint(s) | Most important side effects associated to JAK inhibitors |
|---|---|---|---|---|---|---|
| Baricitinib | JAK1 and JAK2 | BREEZE-AD1 [18] | 624 | 16 wks |
vIGA-AD 0/1 at week 16 - baricitinib 2mg: 11.4% - baricitinib 4mg: 16.8% - placebo: 4.8% |
Increased blood CPK, nasopharyngitis, headache, herpes simplex |
| BREEZE-AD2 [18] | 615 | 16 wks |
vIGA-AD 0/1 at week 16 - baricitinib 2mg: 10.6% - baricitinib 4mg: 13.8% - placebo: 4.5% |
Increased blood CPK, nasopharyngitis, headache | ||
| BREEZE-AD3 [19] | 221 total/partial responders | (16 wks from previous enrollment in BREEZE-AD1 or BREEZE-AD2) plus 52 wks |
vIGA-AD 0/1 at week 16, 36 and 52 Published results at week 52: - baricitinib 2mg: 59.3% - baricitinib 4mg: 47.1% |
Nasopharyngitis, headache, increased blood CPK and diarrhea | ||
| BREEZE-AD4 [20] | 463 | 16 wks |
EASI75 at week 16 - baricitinib 2mg+TCS: 27.6% - baricitinib 4mg+TCS: 31.5% - placebo+TCS: 17.2% |
Nasopharyngitis, headache, upper tract respiratory infections | ||
| BREEZE-AD7 [21] | 329 | 16 wks |
vIGA-AD 0/1 at week 16 - baricitinib 2mg+TCS: 24.0% - baricitinib 4mg+TCS: 31.0% - placebo+TCS: 15.0% |
Nasopharyngitis, folliculitis, Herpes Simplex infection, upper respiratory tract infection, acne, diarrhea, and back pain | ||
| Upadacitinib | JAK1 | Measure Up 1 [24] | 847 | 16 wks |
EASI75 at week 16 - upadacitinib 15mg: 69.6% - upadacitinib 30mg: 79.9% - placebo: 16.3% vIGA-AD 0/1 at week 16 - upadacitinib 15mg: 48.1% - upadacitinib 30mg: 62.0% - placebo: 8.4% |
Acne, upper respiratory tract infections, nasopharyngitis, headache and increased blood CPK |
| Measure Up 2 [24] | 836 | 16 wks |
EASI75 at week 16 - upadacitinib 15mg: 60.1% - upadacitinib 30mg: 72.9% - placebo: 13.3% vIGA-AD 0/1 at week 16 - upadacitinib 15mg: 38.8% - upadacitinib 30mg: 52.0% - placebo: 4.7% |
Acne, upper respiratory tract infections, nasopharyngitis, headache and increased blood CPK | ||
| AD Up [25,26] | 901 | 52 wks |
EASI75 at week 16 - upadacitinib 15mg+TCS: 64.6% - upadacitinib 30mg+TCS: 77.1% - placebo+TCS: 26.4% vIGA-AD 0/1 at week 16 - upadacitinib 15mg+TCS: 39.6% - upadacitinib 30mg+TCS: 58.6% - placebo+TCS: 10.9% |
Acne, nasopharyngitis, increased blood CPK, upper respiratory tract infection, Herpes Simplex infection | ||
| Heads Up [27] | 692 | 24 wks |
EASI75 at week 16 - upadacitinib 30mg: 71.0% - dupilumab: 61.1% |
Acne, upper respiratory tract infections, nasopharyngitis, increased blood CPK | ||
| Abrocitinib | JAK1 | JADE MONO-1 [28] | 387 | 12 wks |
EASI75 at week 12 - abrocitinib 100mg: 40.0% - abrocitinib 200mg: 63.0% - placebo: 12.0% IGA 0/1 at week 12 - abrocitinib 100mg: 24.0% - abrocitinib 200mg: 44.0% - placebo: 8.0% |
Nausea, nasopharyngitis, headache, upper respiratory tract infection |
| JADE MONO-2 [29] | 391 | 12 wks |
EASI75 at week 12 - abrocitinib 100mg: 45.0% - abrocitinib 200mg: 61.0% - placebo: 10.0% IGA 0/1 at week 12 - abrocitinib 100mg: 28.0% - abrocitinib 200mg: 38.0% - placebo: 9.0% |
Nausea, nasopharyngitis | ||
| JADE COMPARE [30] | 838 | 16 wks |
EASI75 at week 12 (vs. placebo) - abrocitinib 100mg+TCS: 58.7% - abrocitinib 200mg+TCS: 70.3% - dupilumab: 58.1% - placebo+TCS: 27.1% IGA 0/1 at week 12 (vs. placebo) - abrocitinib 100mg+TCS: 36.6% - abrocitinib 200mg+TCS: 48.4% - dupilumab: 36.5% - placebo+TCS: 14.0% |
Nausea, nasopharyngitis, upper respiratory tract infection, headache, acne, Herpes Zoster, thrombocytopenia | ||
| JADE REGIMEN [31] | 1233 (798 after a 12-week induction period with abrocitinib 200mg) | 52 wks |
Proportion of patients that did not loss EASI50 and had IGA score <3 at week 52 - abrocitinib 100mg: 57.4% - abrocitinib 200mg: 81.1% - placebo: 19.1% |
Nausea, nasopharyngitis, acne, upper respiratory tract infections, increased blood CPK | ||
| JADE TEEN [32] | 285 | 12 wks |
EASI75 at week 12 - abrocitinib 100mg+TCS: 68.5% - abrocitinib 200mg+TCS: 72.0% - placebo+TCS: 41.5% IGA 0/1 at week 12 - abrocitinib 100mg+TCS: 41.6% - abrocitinib 200mg+TCS: 46.2% - placebo+TCS: 24.5% |
Nausea, upper respiratory tract infections, headache, and nasopharyngitis |
CPK = creatine phosphokinase; EASI = Eczema Area and Severity Index; EASI-50 = Improvement of 50% in EASI compared to baseline; EASI-75 = Improvement of 75% in EASI compared to baseline; IGA 0/1 = Investigator Global Assessment score of 0 or 1; JAK = Janus Kinase; TCS = topical corticosteroids; vIGA-AD 0/1 = Validated Investigator’s Global Assessment for Atopic Dermatitis score of 0 or 1; wks = weeks