Table 5.
Safety of UPA in Other Immunomediated Diseases
| N of Patients, (M/F) | Duration, (Weeks) | Randomization | AEs, N (%) | SAEs, N (%) | Infections, N (%) | HZ Infection, N (%) | Malignancy, N (%) | MACEs, N (%) | VTE, N (%) | |
|---|---|---|---|---|---|---|---|---|---|---|
| RA | ||||||||||
| Genovese71 | 300 (63/237) | 12 | 50 PBO, 50 UPA 3mg, 50 UPA 6mg, 50 UPA 12mg, 50 UPA 18mg, 50 UPA 24mg (twice daily) | 17–29 (35–59) UPA 13 (26) PBO |
0–3 (2–6) UPA 0 PBO |
7–12 (14–24) UPA 7 (14) PBO |
0–2 (0–4) UPA 0 PBO |
0–1 (0–2) UPA 0 PBO |
NA | NA |
| Kremer72 | 276 (60/216) | 12 | 56 PBO, 55 UPA 3mg, 55 UPA 6mg, 55 UPA 12mg, 55 UPA 18m, 55 UPA 24mg (twice daily) | 26–39 (47–71) UPA 25 (45) PBO |
0–2 (2–4) UPA 1 (2) PBO |
11–22 (20–40) UPA 13 (23) PBO |
0–1 (0–2) UPA 2 (4) PBO |
0–1 (2) UPA 0 PBO |
NA | NA |
| Mohamed20 | 114 (93/21) | 2 | − 56 healthy subjects randomized to UPA 1mg, 3mg, 6mg, 12mg, 24mg, 36mg, 48mg (study 1) − 44 healthy subjects randomized to UPA 3mg, 6mg, 12mg, 24mg − 14 RA patients (study 2) |
Study 1 1–2 (16.7–33.3) UPA 3 (21.4) PBO Study 2 2–4 (25–50) UPA 7 (58.3) PBO |
NA | Study 2 0–1 (12.5) UPA 2 (16.7) PBO |
NA | NA | NA | NA |
| Brumester42 | 661 (141/520) | 12 | 221 UPA 15mg QD 219 UPA 30mg QD 221 PBO |
125 (57) UPA 15mg 118 (54) UPA 30mg 108 (49) PBO |
9 (4) UPA 15mg 6 (3) UPA 30mg 5 (2) PBO |
64 (29) UPA 15mg 69 (32) UPA 30mg 47 (21) PBO |
1 (<1) UPA 15mg 2 (1) UPA 30mg 1 (<1) * PBO |
0 UPA 15mg 2 (1) UPA 30mg 0 PBO |
0 UPA 15mg 1 (<1) UPA 30mg 0 PBO |
0 UPA 15mg 0 UPA 30mg 0 PBO |
| Genovese41 | 498 (80/418) | 24 | − 164 UPA 15 mg QD − 165 UPA 30 mg QD − 85 PBO for 12 weeks, then UPA 15 mg QD for 12 weeks − 84 PBO for 12 weeks, then UPA 30 mg QD for 12 weeks |
0–12 wk: 91 (55) UPA 15mg 111 (67) UPA 30mg 95 (56) PBO 12–24 wk: 82 (53) UPA 15mg 83 (56) UPA 30mg 30 (42) PBO to UPA 15mg 50 (67) PBO to UPA 30mg |
0–12 wk: 8 (5) UPA 15mg 12 (7) UPA 30mg 0 PBO 12–24 wk: 5 (3) UPA 15mg 5 (3) UPA 30mg 5 (7) PBO to UPA 15mg 5 (7) PBO to UPA 30mg |
0–12 wk: 54 (33) UPA 15mg 55 (33) UPA 30mg 51 (30) PBO 12–24 wk: 43 (28) UPA 15mg 47 (32) UPA 30mg 16 (22) PBO to UPA 15mg 31 (41) PBO to UPA 30mg |
0–12 wk: 1 (1) UPA 15mg 4 (2) UPA 30mg 1 (1) PBO 12–24 wk: 2 (1) UPA 15mg 2 (1) UPA 30mg 1 (1) PBO to UPA 15mg 0 PBO to UPA 30mg |
0–12 wk: 2 (1%) UPA 15mg 1 (1%) UPA 30mg 0 PBO 12–24 wk: 1 (1) UPA 15mg 0 UPA 30mg 0 PBO to UPA 15mg 0 PBO to UPA 30mg |
0–12 wk: 1 (1%) UPA 15mg 0 UPA 30mg 0 PBO 12–24 wk: 0 UPA 15mg 0 UPA 30mg 0 PBO to UPA 15mg 1 (1) PBO to UPA 30mg |
NA |
| Smolen39 | 648 (125/523) | 14 | 217 UPA 15mg 215 UPA30mg 216 MTX |
103 (47) UPA 15mg 105 (49) UPA 30mg 102 (47) MTX |
11 (5) UPA 15mg 6 (3) UPA 30mg 6 (3) MTX |
42 (19) UPA 15mg 54 (25) UPA 30mg 57 (26) MTX |
3 (1) UPA 15mg 6 (3) UPA 30mg 1 (<1) MTX |
2 (1) UPA 15mg 0 UPA 30mg 1 (<1) MTX |
1 (<1) UPA 15mg 2 (1) UPA 30mg 0 MTX |
1 (<1) UPA 15mg 0 UPA 30mg 0 MTX |
| Fleishman73 | 1629 NA | 48 | 651 UPA 15mg+ background MTX 327 ADA + background MTX 651 PBO + background MTX |
266.6/100 PYs UPA 15mg 294.8/100 PYs ADA |
12.9/100 PYs UPA 15mg 15.6/100 PYs ADA |
86.8/100 PYs UPA 15mg 79.1/100 PYs ADA |
3.1/100 PYs UPA 15mg 1.3/100 PYs ADA |
0.4/100 PYs UPA 15mg 0.6/100 PYs ADA |
0.4/100 PYs UPA 15mg 0.4/100 PYs ADA |
0.3/100 PYs UPA 15mg 1.1/100 PYs ADA |
| AD | ||||||||||
| Guttmann-Yassky43 | 167 131/63) | 16 | 42 UPA 7.5mg 42 UPA 15mg 42 UPA 30mg 41 PBO |
31 (74) UPA 7.5 32 (76) UPA 15mg 33 (79) UPA 30mg 25 (63) PBO |
2 (4.8) UPA 7.5 1 (2.4) UPA 15mg 0 UPA 30mg 1 (2.5) PBO |
31 (74) UPA 7.5 32 (76) UPA 15mg 33 (79) UPA 30mg 25 (63) PBO |
22 (52) UPA 7.5mg 18 (63) UPA 15mg 17 (41) UPA 30mg 8 (20) PBO |
NA | NA | NA |
| Reich44 | 901 (547/354) | 16 | 300 UPA 15mg 397 UPA 30mg 304 PBO |
215 (72) UPA 15mg 190 (63) UPA 30mg 200 (67) PBO |
4 (1) UPA 15mg 9 (3) UPA 30mg 7 (2) PBO |
NA | 5 (2) UPA 15mg 3 (1) UPA 30mg 3 (1) PBO |
0 UPA 15mg 1 (<1%) UPA 30mg 0 PBO |
0 UPA 15mg 0 UPA 30mg 0 PBO |
0 UPA 15mg 0 UPA 30mg 0 PBO |
| Guttmann-Yassky45 | 847 (456/391) | 16 | 281 UPA 15mg 285 UPA 30mg 281 PBO |
176 (63) UPA 15mg 209 (73) UPA 30mg 166 (59) PBO |
6 (2) UPA 15mg 8 (3) UPA 30mg 8 (3) PBO |
NA | 5 (2) UPA 15mg 6 (2) UPA 30mg 0 PBO |
1 (<1) UPA 15mg 2 (2) UPA 30mg 0 PBO |
0 UPA 15mg 0 UPA 30mg 0 PBO |
0 UPA 15mg 0 UPA 30mg 0 PBO |
| Guttmann-Yassky45 | 836 (471/365) | 16 | 276 UPA 15mg 282 UPA 30mg 278 PBO |
166 (60) UPA 15mg 173 (61) UPA 30mg 146 (53) PBO |
5 (2) UPA 15mg 7 (3) UPA 30mg 8 (3) PBO |
NA | 6 (2) UPA 15mg 3 (1) UPA 30mg 2 (1) PBO |
2 (1) UPA 15mg 1 (<1) UPA 30mg 0 PBO |
0 UPA 15mg 0 UPA 30mg 0 PBO |
0 UPA 15mg 0 UPA 30mg 1 (<1) PBO |
| Katoh47 | 272 (211/61) | 14 | 91 UPA 15mg 91 UPA 30mg 90 PBO |
51 (56) UPA 15mg 58 (63) UPA 30mg 38 (42.2) PBO |
1 (1.1) UPA 15mg 1 (1.1) UPA 30mg 1 (1.1) PBO |
NA | 0 UPA 15mg 4 (4.4) UPA 30mg 0 PBO |
0 UPA 15mg 0 UPA 30mg 0 PBO |
NA | 0 UPA 15mg 0 UPA 30mg 0 PBO |
| Blauvelt46 | 692 (375/315) | 16 | 348 UPA 30mg 344 DUPI 300mg |
249 (71.6) UPA 216 (62.8) DUPI |
10 (2.9) UPA 4 (1.2) DUPI |
NA | 7 (2) UPA 3 (0.9) DUPI |
0 UPA 1 (0.3) DUPI |
0 UPA 0 DUPI |
0 UPA 0 DUPI |
| PsA | ||||||||||
| McInnes50 | 1704 (1007/697) | 24 | 429 UPA 15mg 423 UPA 30mg 429 ADA 423 PBO |
287 (66.9) UPA 15mg 306 (72.3) UPA 30mg 278 (64.8) ADA 252 (59.6) PBO |
14 (3.3) UPA 15mg 26 (6.1) UPA 30mg 16 (3.7) ADA 13 (3.1) PBO |
169 (39.4) UPA 15mg 183 (43.3) UPA 30mg 146 (34.0) ADA 140 (33.1) PBO |
4 (0.9) UPA 15mg 5 (1.2) UPA 30mg 0 ADA 3 (0.7) PBO |
1 (0.2) UPA 15mg 3 (0.7) UPA 30mg 3 (0.7) ADA 1 (0.2) PBO |
0 UPA 15mg 0 UPA 30mg 2 (0.5) ADA 1 (0.2) PBO |
0 UPA 15mg 1 (0.2) UPA 30mg 2 (0.5) ADA 1 (0.2) PBO |
| Mease49 | 641 (293/348) | 24 | 211 UPA 125mg 218 UPA 30mg 212 PBO |
135 (64) UPA 15mg 170 (78) UPA 30mg 139 (65.6) PBO |
12 (5.7) UPA 15mg 18 (8.3) UPA 30mg 4 (1.9) PBO |
71 (33.6) UPA 15mg 108 (49.5) UPA 30mg 73 (34.4) PBO |
3 (1.4) UPA 15mg 8 (3.7) UPA 30mg 2 (0.9) PBO |
3 (1.4) UPA 15mg 3 (1.4)) UPA 30mg 0 PBO |
0 1 (0.5) UPA 15mg 0 UPA 30mg 0 PBO |
0 1 (0.5) UPA 15mg 0 UPA 30mg 0 PBO |
| AS | ||||||||||
| van der Heijde51 | 187 (132/75) | 14 | 93 UPA 15mg 94 PBO |
58 (62) UPA 52 (55) PBO |
1 (1) UPA 1 (1) PBO |
19 (20) UPA 26 (28) PBO |
0 UPA 0 PBO |
0 UPA 0 PBO |
0 UPA 0 PBO |
0 UPA 0 PBO |
Note: *One case of primary varicella zoster virus infection.
Abbreviations: M, males; F, females; AEs, adverse events; SAEs, serious adverse events; HZ, herpes zoster; MACEs, major adverse cardiovascular event; VTE, venous thromboembolism; RA, rheumatoid arthrithis; AD, atopic dermatitis; PsA, psoriatic arthritis; AS, ankylosing spondylitis; PBO, placebo; UPA, upadacitinib; MTX, methotrexate; ADA, adalimumab; DUPI, dupilumab; PYs, patient-years; NA, not available.