Table 1.
Randomized clinical trials on inhibitors of the IL-23/IL-17 axis in Psoriasis and Psoriatic Arthritis. Ust: Ustekinumab; Bri: Briakinumab; MTX: Methotrexate; Gus: Guselkumab; Ada: Adalimumab; Ris: Risankizumab; Til: Tildrakizumab; Eta: Etanercept; Sec: Secukinumab; Ixe: Ixekizumab; Bro: Brodalumab; PASI: Psoriasis Area and Severity Index; ACR: American College of Rheumatology; IGA: Investigator’s Global Assessment.
| Agents | Name of the Study and Reference | Condition | Trial Phase | Treatment Arm | Control Arm | Primary Endpoint | |
|---|---|---|---|---|---|---|---|
| Skin PASI75 at Week 12 Unless Otherwise Specified |
Joint-Related ACR20 Unless Otherwise Specified |
||||||
| Anti-IL12/23p40 | |||||||
| Ustekinumab (CNTO 1275, Stelara) |
PHOENIX 1 NCT00267969 [92] |
Psoriasis | III | Ust 45 mg (n = 255) Ust 90 mg (n = 256) |
Placebo (n = 255) | Ust 45 mg 67.1% Ust 90 mg 66.4% Placebo 3.1% |
- |
|
PHOENIX 2 NCT00307437 [93,95] |
Psoriasis | III | Ust 45 mg (n = 409) Ust 90 mg (n = 411) |
Placebo (n = 410) | Ust 45 mg 66.7% Ust 90 mg 75.7% Placebo 3.7% |
- | |
|
PSUMMIT1 NCT01009086 [99] |
PsA | III | Ust 45 mg (n = 205) Ust 90 mg (n = 204) |
Placebo (n = 206) | Ust 45 mg 57.2% Ust 90 mg 62.4% Placebo 11.0% |
At week 24: Ust 45 mg 42.4% Ust 90 mg 49.5% Placebo 22.8% |
|
|
PSUMMIT 2 NCT01077362201 [100] |
PsA | III | Ust 45 mg (n = 103) Ust 90 mg (n = 105) |
Placebo (n = 104) | At week 24: Ust 45 mg 51.3% Ust 90 mg 55.6% Placebo 5% |
At week 24: Ust 45 mg 43.7% Ust 90 mg 43.8% Placebo 20.2% |
|
| Briakinumab (ABT-874, Ozespa) |
NCT00691964 [104] |
Psoriasis | III | Bri 200 mg × 2 then 100 mg (n = 138) | Etanercept 50 mg twice-weekly (n = 141) Placebo (n = 68) |
Bri 81.9% Eta 56.0% Placebo 7.4% |
- |
|
NCT00679731 [105] |
Psoriasis | III | Bri 200 mg × 2 then 100 mg (n = 154) | MTX 5 to 25 mg weekly (n = 163) | (At week 24) Bri 81.8% MTX 39.9% |
- | |
|
NCT00710580 [131] |
Psoriasis | III | Bri 200 mg × 2 then 100 mg (n = 138) | Etanercept 50 mg twice-weekly (n = 141) Placebo (n = 68) |
Bri 80.6% Eta 39.6% Placebo 6.9% |
- | |
|
NCT00570986 [106] |
Psoriasis | III | Bri 200 mg × 2 then 100 mg (n = 981) | Placebo (484) | Bri 80.7% Placebo 4.5% |
- | |
| Anti-IL23p19 | |||||||
| Guselkumab (CNTO 1959; Tremfya) |
NAVIGATE NCT02203032 [112] |
Psoriasis | III | Ust non-responder patients at Week 12 (total n = 268): Gus 100 mg (n = 135) Ust (n = 133) |
Ust responder patients at Week 12 (n = 585) | Visits at which patients achieved IGA 0/1 and >2-grade improvement: Gus 1.5 ± 1.6 Ust 0.7 ± 1.3 |
- |
|
VOYAGE-1 NCT02207231 [110] |
Psoriasis | III | Gus 100 mg (n = 329) | Placebo (weeks 0, 4, 12) then Gus 100 mg (weeks 16, 20) (n = 174) Ada 80 mg (n = 334) |
PASI75 at week 16: Gus 91.2% Placebo 5.7% Ada 73.1% |
- | |
|
VOYAGE-2 NCT02207244 [111] |
Psoriasis | III | Gus 100 mg (n = 496) | Placebo (weeks 0, 4, 12) then Gus 100 mg (weeks 16, 20) (n = 248) Ada 80 mg (n = 248) |
PASI75 at week 16: Gus 86.3% Placebo 8.1% Ada 68.5% |
- | |
| Risankizumab (BI 655066) |
NCT02054481 [114] |
Psoriasis | II | Ris 18 mg (n = 43) Ris 90 mg (n = 41) Ris 180 mg (n = 42) |
Ust (n = 40) | PASI90 at week 12: Ris 90 and 180 mg 77% Ust 40% |
- |
|
UltIMMa-1 NCT02684370 (Not yet completed) |
Psoriasis | III | Ris | Ust Placebo |
Not yet completed | - | |
| Tildrakizumab (MK-3222) |
reSURFACE-1 NCT01722331 [116] |
Psoriasis | III | Til 100 mg (n = 309) Til 200 mg (n = 308) |
Placebo (n = 155) | Til 100 mg 62% Til 200 mg 64% Placebo 6% |
- |
|
reSURFACE-2 NCT01729754 [116] |
Psoriasis | III | Til 100 mg (n = 307) Til 200 mg (n = 314) |
Placebo (n = 156) Eta (n = 313) |
Til 100 mg 61% Til 200 mg 66% Placebo 6% Eta 48% |
- | |
| Anti-IL17A | |||||||
| Secukinumab (AIN457, Cosentyx) |
ERASURE NCT01365455 [118] |
Psoriasis | III | Sec 150 mg (n = 245) Sec 300 mg (n = 245) |
Placebo (n = 248) | Sec 150 mg 71.6% Sec 300 mg 81.6% Placebo 4.5% |
- |
|
FIXTURE NCT01358578 [118] |
Psoriasis | III | Sec 150 mg (n = 327) Sec 300 mg (n = 327) |
Placebo (n = 326) | Sec 150 mg 67.0% Sec 300 mg 77.1% Placebo 4.9% |
- | |
|
FUTURE1 NCT01392326 [119] |
PsA | III | Sec 75 mg (n = 202) Sec 150 mg (n = 202) |
Placebo (n = 202) | PASI75 at week 24: Sec 75 mg 64.8% Sec 150 mg 61.1% Placebo 8.3% |
ACR20 at week 24: Sec 75 mg 50% Sec 150 mg 50.5% Placebo 17.3% |
|
|
FUTURE2 NCT01752634 [123] |
PsA | III | Sec 75 mg (n = 99) Sec 150 mg (n = 100) Sec 300 mg (n = 100) |
Placebo (n = 98) | PASI75 at week 24: Sec 150 mg 48% Sec 300 mg 63% Placebo 16% |
ACR20 at week 24: Sec 75 mg 29% Sec 150 mg 51% Sec 300 mg 54% Placebo 15% |
|
| Ixekizumab (LY2439821, Taltz) |
UNCOVER-1 NCT01474512 [126] |
Psoriasis | III | Ixe 80 mg q2wk (n = 433) Ixe 80 mg q4wk (n = 432) |
Placebo (n = 431) | Ixe 80 mg q2wk 89.1% Ixe 80 mg q4wk 82.6% Placebo 3.9% |
- |
|
UNCOVER-2 NCT01597245 [126] |
Psoriasis | III | Ixe 80 mg q2wk (n = 351) Ixe 80 mg q4wk (n = 347) |
Eta 50 mg twice-weekly (n = 358) Placebo (n = 168) |
Ixe q2wk 89.7% Ixe q4wk 77.5% Eta 41.6% Placebo 2.4% |
- | |
|
UNCOVER-3 NCT01646177 [126] |
Psoriasis | III | Ixe 80 mg q2wk (n = 385) Ixe 80 mg q4wk (n = 386) |
Eta 50 mg twice-weekly (n = 382) Placebo (n = 193) |
Ixe q2wk 87.3% Ixe q4wk 84.2% Eta 53.4% Placebo 7.3% |
- | |
|
SPIRIT-P1 NCT01695239 [127] |
PsA | III | Ixe 80 mg q2wk (n = 103) Ixe 80 mg q4wk (n = 107) |
Ada 40 mg q2wk (n = 101) Placebo (n = 106) |
PASI75 at week 24: Ixe q2wk 79.7% Ixe q4wk 71.2% Ada 54.4% Placebo 10.4% |
ACR20 at week 24: Ixe q2wk 62.1% Ixe q4wk 57.9% Ada 57.4% Placebo 30.2% |
|
| Anti-IL17RA | |||||||
| Brodalumab (AMG 827, Siliq) |
AMAGINE-2 NCT01708603 [129] |
Psoriasis | III | Bro 140 mg (n = 610) Bro 210 mg (n = 612) |
Ust 45 mg (n = 300) Placebo (n = 309) |
Bro 140 mg 67% Bro 210 mg 86% Ust 70% Placebo 8% |
- |
|
AMAGINE-3 NCT01708629 [132] |
Psoriasis | III | Bro 140 mg (n = 629) Bro 210 mg (n = 624) |
Ustekinumab 45 mg (n = 313) Placebo (n = 315) |
Bro 140 mg 69% Bro 210 mg 85% Ust 69% Placebo 6% |
- | |
| NCT01516957 | PsA | II | Bro 280 mg (n = 56) Bro 140 mg (n = 57) |
Placebo (n = 55) | - | Bro 280 mg 39% Bro 140 mg 37% Placebo 18% |
|
|
AMVISION-2 NCT02024646 (Not yet completed) |
PsA | III | Bro 140 mg Bro 210 mg |
Placebo | Not yet completed | Not yet completed | |