Table 3.
Oral JAK inhibitors for atopic dermatitis.
| JAK inhibitors | FDA approval for AD | RCT | Inclusion | Treatment | Treatment period | Patients (n) | Sex (M/F) | Age | Baseline EASI score | Primary endpoint | Results |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Upadacitinib (JAK1) |
V | Phase 2b RCT (NCT02925117) (103) |
Adults with moderate-to-severe AD | Upadacitinib 30mg QD Upadacitinib 15mg QD Upadacitinib 7.5mg QD Placebo |
88 weeks (16 weeks treatment+72 weeks withdraw) |
42 42 42 41 |
22/20 30/12 28/14 24/17 |
39.9 (15.3) 38.5 (15.2) 41.5 (15.4) 39.9 (17.5) |
28.2 (11.6) 31.4 (12.3) 31.4 (15.8) 32.6 (14.5) |
%EASI at Week 16 | -74 (6.1)% -62 (6.1)% -39 (6.2)% -23 (6.4)% |
| Phase 3 RCT (Measure Up 1, NCT03569293) (104) |
Adults with moderate-to-severe AD | Upadacitinib 30mg QD Upadacitinib 15mg QD Placebo |
16 weeks | 285 281 281 |
155/130 157/124 144/137 |
33.6 (NA) 34.1 (NA) 34.4 (NA) |
29.0 (11.1) 30.6 (12.8) 28.8 (12.6) |
EASI75 at Week 16 | 227 (79.7%) 196 (69.6%) 46 (16.3%) |
||
| Phase 3 RCT (Measure Up 2, NCT03607422) (104) |
Adults with moderate-to-severe AD | Upadacitinib 30mg QD Upadacitinib 15mg QD Placebo |
16 weeks | 282 276 278 |
162/120 155/121 154/124 |
34.1 (NA) 33.3 (NA) 33.4 (NA) |
29.7 (12.2) 28.6 (11.7) 29.1 (12.1) |
EASI75 at Week 16 | 206 (72.9%) 166 (60.1%) 37 (13.3%) |
||
| Phase 3 RCT (AD Up, NCT03568318) (105) |
Age of 12-75 with AD | Upadacitinib 30mg+TCS Upadacitinib 15mg QD+TCS Placebo+TCS |
16 weeks treatment+260 weeks BE | 297 300 304 |
190/107 179/121 178/126 |
35.5 (NA) 32.5 (NA) 34.3 (NA) |
29.7 (11.8) 29.2 (11.8) 30.3 (13.0) |
EASI75 at Week 16 | 229 (77.1%) 194 (64.6%) 80 (26.4%) |
||
| Phase 3b RCT (Heads Up, NCT03738397) (106) |
Adults with moderate-to-severe AD | Upadacitinib 30mg QD Dupilumab∫ |
24 weeks | 348 344 |
183/165 194/150 |
36.6 (14.6) 36.9 (14.1) |
30.8 (12.5) 28.8 (11.5) |
EASI75 at Week 16 | 247 (71.0%) 210 (61.1%) |
||
| Baricitinib/ LY3009104 (JAK1/2) |
X | Phase 2b RCT (NCT02576938) (107) |
Adults with moderate-to-severe AD | Baricitinib 4mg QD+TCS Baricitinib 2mg QD+TCS Placebo+TCS |
16 weeks | 38 37 49 |
22/16 22/15 35/14 |
32.5 42.0 35.0* |
19.5 22.1 22.1* |
EASI50 at Week 16 | 23 (61%) 21 (57%) 18 (37%) |
| Phase 3 RCT (BREEZE-AD1, NCT03334396) (80) |
Adults with moderate-to-severe AD | Baricitinib 4mg QD Baricitinib 2mg QD Baricitinib 1mg QD Placebo |
16 weeks | 125 123 127 249 |
83/4/2 82/41 78/49 148/101 |
37 (12.9) 35 (13.7) 36 (12.4) 35 (12.6) |
32 (12.7) 31 (11.7) 29 (11.8) 32 (13.0) |
vIGA-AD 0/1 at Week 16 | 21 (16.8%) 14 (11.4%) 15 (11.8%) 12 (4.8%) |
||
| Phase 3 RCT (BREEZE-AD2, NCT03334422) (80) |
Adults with moderate-to-severe AD | Baricitinib 4mg QD Baricitinib 2mg QD Baricitinib 1mg QD Placebo |
16 weeks | 123 123 125 244 |
82/41 65/58 80/45 154/90 |
34 (14.1) 36 (13.2) 33 (10.0) 35 (13.0) |
33 (12.7) 35 (16.0) 33 (12.7) 33 (12.8) |
vIGA-AD 0/1 at Week 16 | 17 (13.8%) 13 (10.6%) 11 (8.8%) 11 (4.5%) |
||
| Phase 3 LTE (BREEZE-AD3, NCT03334435) (108) |
Adults with moderate-to-severe AD | Baricitinib 4mg QD Baricitinib 2mg QD |
68 weeks | 70 54 |
42/28 28/26 |
36.7 (15.5) 32.8 (12.7) |
28.1 (10.6) 24.9 (8.7) |
vIGA-AD 0/1 at Week 68 | 33 (47.1%) 32 (59.3%) |
||
| Phase 3 RCT (BREEZE-AD4, NCT03428100) (109) |
Adults with moderate-to-severe AD | Baricitinib 4mg QD+TCS Baricitinib 2mg QD+TCS Baricitinib 1mg QD+TCS Placebo+TCS |
16 weeks | 92 185 93 93 |
57/35 133/52 58/35 49/44 |
38.7 (13.3) 37.3 (13.6) 38.9 (14.0) 38.7 (13.6) |
NA | EASI75 at Week 16 | 29 (31.5%0 51 (27.6%) 21 (22.6%) 16 (17.2%) |
||
| Phase 3 RCT (BREEZE-AD5, NCT03435081) (110) |
Adults with moderate-to-severe AD | Baricitinib 2mg QD Baricitinib 1mg QD Placebo |
16 weeks | 146 147 147 |
69/77 75/72 80/67 |
40 (15) 40 (17) 39 (17) |
26.6 (11) 27.7 (12) 27.0 (11) |
EASI75 at Week 16 | 44 (30%) 19 (13%) 12 (8%) |
||
| Phase 3 OLLTE (BREEZE-AD6, NCT03559270) (111) |
Adults with moderate-to-severe AD | Ongoing | 16 weeks | NA | NA | NA | NA | EASI75 at Week 16 | NA | ||
| Phase 3 RCT (BREEZE-AD7, NCT03733301) (112) |
Adults with moderate-to-severe AD | Baricitinib 4mg QD+TCS Baricitinib 2mg QD+TCS Placebo+TCS |
16 weeks | 111 109 109 |
75/36 70/39 71/38 |
33.9 (11.4) 33.8 (12.8) 33.7 (13.2) |
30.9 (12.6) 29.3 (11.9) 28.5 (12.3) |
vIGA-AD 0/1 at Week 16 | 34 (31%) 26 (24%) 16 (15%) |
||
| Abrocitinib/ PF-04965842 (JAK1) |
V | Phase 2 RCT (NCT02780167) (113) |
Adults with moderate-to-severe AD | Abrocitinib 200mg QD Abrocitinib 100mg QD Abrocitinib 30mg QD Abrocitinib 10mg QD Placebo+TM |
12 weeks | 55 56 51 49 56 |
28/27 31/25 22/29 21/28 21/35 |
38.7 (17.6) 41.1 (15.6) 37.6 (15.9) 44.3 (15.9) 42.6 (15.1) |
24.6 (13.5) 26.7 (11.8) 22.1 (10.7) 28.1 (13.1) 25.4 (12.9) |
vIGA 0/1 at Week 12 | 21 (43.8%) 16 (29.6%) 4 (8.9%) 5 (10.9%) 3 (5.8%) |
| Phase 3 RCT (JADE MONO-1,NCT03349060) (114) |
Age≧12 with moderate-to-severe AD | Abrocitinib 200mg QD Abrocitinib 100mg QD Placebo |
12 weeks | 154 156 77 |
81/73 90/66 49/28 |
33.0 (17.4) 32.6 (15.4) 31.5 (14.4) |
30.6 (14.1) 31.3 (13.6) 28.7 (12.5) |
vIGA 0/1 at Week 12 / EASI75 at Week 12 |
67 (44%) 37 (24%) 6 (8%) 96 (63%) 62 (40%) 9 (12%) |
||
| Phase 3 RCT (JADE MONO-2,NCT03575871) (115) |
Age≧12 with moderate-to-severe AD | Abrocitinib 200mg QD Abrocitinib 100mg QD Placebo |
12 weeks | 155 158 78 |
88/67 94/64 47/31 |
33.5 (14.7) 37.4 (15.8) 33.4 (13.8) |
29.0 (12.4) 28.4 (11.2) 28.0 (10.2) |
vIGA 0/1 at Week 12 / EASI75 at Week 12 |
55 (38.1%) 44 (28.4%) 7 (9.1%) / 94 (61.0%) 69 (44.5%) 8 (10.4%) |
||
| Phase 3 RCT (JADE TEEN, NCT03796676) (116) |
Age of 12-17 with moderate-to-severe AD | Abrocitinib 200mg QD+TM Abrocitinib 100mg QD+TM Placebo+TM |
12 weeks | 94 95 96 |
56/38 45/50 44/52 |
15.0 16.0 14.0* |
29.5 (12.2) 31.0 (12.8) 29.2 (12.7) |
vIGA 0/1 at Week 12 / EASI75 at Week 12 |
43 (46.2%) 37 (41.6%) 23 (24.5%) / 67 (72.0%) 61 (68.5%) 39 (41.5%) |
||
| Phase 3 RCT (JADE COMPARE, NCT03720470) (117) |
Adults with moderate-to-severe AD | Abrocitinib 200mg QD+TM Abrocitinib 100mg QD+TM Dupilumab∫+TM Placebo |
12 weeks | 238 226 242 131 |
120/118 104/122 108/134 77/54 |
37.3 (14.8) 38.8 (14.5) 37.1 (14.6) 37.4 (15.2) |
30.3 (13.5) 32.1 (13.1) 30.4 (12.0) 31.0 (12.6) |
vIGA 0/1 at Week 12 / EASI75 at Week 12 |
106 (48.4%) 86 (36.6%) 88 (36.5%) 18 (14.0%) / 154 (70.3%) 138 (58.7%) 140 (58.1%) 35 (27.1%) |
||
| Phase 3 RCT (JADE REGIMEN, NCT03627767) (118) |
Age≧12 with moderate-to-severe AD | Abrocitinib 200mg QD Abrocitinib 100mg QD Placebo |
54 weeks (12 weeks OLi, 30 weeks treatment, 12 weeks OLr) |
266 265 267 |
150/116 148/117 141/126 |
28.0 29.0 29.0* |
27.2 27.7 26.9* |
the rate of flare-up§ | 44 (16.5%) 105 (39.6%) 207 (77.5%) |
||
| Phase 3 LTE (JADE EXTEND, NCT03422822) (119) |
Adults with moderate-to-severe AD | Abrocitinib 200mg QD Abrocitinib 100mg QD |
12 weeks | 73 130 |
35/38 61/69 |
37.3 (14.5) 38.6 (14.8) |
31.2 (12.4) 29.6 (11.2) |
vIGA 0/1 at Week 12 | Prior dupilumab responder 25 (83.3%) 30 (76.9%) / Nonresponder 17 (47.2%) 25 (35.2%) |
||
| Phase 3 RCT (JADE DARE, NCT04345367) (120) |
Adults with moderate-to-severe AD | Abrocitinib 200mg QD Dupilumab∫ |
26 weeks | 362 365 |
193/169 204/161 |
34.6 (14.6) 35.5 (13.3) |
28.1 (11.5) 28.1 (11.9) |
PP-NRS4 at week 2 / EASI-90 at week 4 |
172 (48%) 93 (26%) / 101 (29%) 53 (15%) |
||
| Gusacitinib/ASN002 (JAKs, SYK) |
X | Phase 1b RCT (NCT03139981) |
Adults with moderate-to-severe AD | ASN002 80mg QD ASN002 40mg QD ASN002 20mg QD Placebo |
4 weeks | 9 9 9 9 |
5/4 5/4 5/4 3/6 |
33.1 (10.4) 42.4 (13.9) 38.2 (14.4) 29.9 (9.3) |
28.2 (11.7) 21.8 (6.2) 29.0 (13.5) 21.6 (6.2) |
TEAEs | Headache, nausea, diarrhea |
| Phase 2b RCT (NCT03531957) (121) |
Adults with moderate-to-severe AD | ASN002 80mg QD ASN002 40mg QD ASN002 20mg QD Placebo |
36 weeks (12 weeks treatment+24 weeks OLE) |
NA | NA | NA | NA | cEASI at Week 12 | NA | ||
| Ivarmacitinib/ SHR0302 (JAK1) |
X | Phase 2 RCT (NCT04162899) (122) |
Adults with moderate-to-severe AD | SHR0302 8mg QD SHR0302 4mg QD Placebo |
12 weeks | 35 35 35 |
23/12 20/15 26/9 |
35.2 (14.8) 38.5 (14.8) 30.3 (12.6) |
25.4 (11.3) 30.5 (15.7) 28.2 (12.1) |
vIGA 0/1 at Week 12 | 19 (54.3%) 9 (25.7%) 2 (5.7%) |
Data are n, n (%), mean, mean (SD), or median*.
∫ 300 mg dupilumab was injected subcutaneously every 2 weeks after a loading dose of 600 mg.
§ Defined as ≥50% reduction in initial EASI response at week 12 with a new IGA score of ≥2
❡ AD, atopic dermatitis; BE, blinded extension; cEASI, change of EASI score from baseline; EASI50/75, ≥50/75% improvement of EASI score from baseline; JAK, Janus kinase; LOR, loss of response; LTE, long-term extension; OL, open-label; OLi, open-label induction period; OLr, open-label rescue period; PP-NRS4, 4 point or more improvement in Peak Pruritus Numerical Rating Scale; SYK, spleen tyrosine kinase; TCS, topical corticosteroid; TM, topical medication; vIGA-AD 0/1, validated Investigator’s Global Assessment of AD score of 0 or 1 with a 2-point or greater improvement from baseline. NA, Not Available.