| Literature DB >> 30425963 |
Eric J Yang1,2, Kristen M Beck1, Wilson Liao1.
Abstract
Secukinumab is a human monoclonal antibody targeting IL-17A that has been approved for three indications: moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In Phase III clinical trials for each of these three indications, secukinumab has proven to be both highly efficacious and well-tolerated. However, several biologic medications are currently approved for the treatment of moderate-to-severe plaque psoriasis, and many demonstrate excellent efficacy and safety. Due to this wide selection, it is often unclear how to choose biologics for specific patients. Important considerations in biologic selection include clinical efficacy, safety, cost, convenience, onset of action, and management of comorbid disease. This article aims to outline the key considerations in patient selection for the treatment of plaque psoriasis with secukinumab.Entities:
Keywords: IL-17 inhibitor; IL-17A; biologics; patient selection; psoriasis; secukinumab
Year: 2018 PMID: 30425963 PMCID: PMC6202001 DOI: 10.2147/PTT.S146004
Source DB: PubMed Journal: Psoriasis (Auckl) ISSN: 2230-326X
Summary of key Phase III clinical trial results of secukinumab for the treatment of plaque psoriasis at week 12
| Trial | Year | n | Treatment (n) | IGA 0/1 | PASI 75 | PASI 90 | PASI 100 |
|---|---|---|---|---|---|---|---|
|
| |||||||
| ERASURE | 2014 | 738 | Secukinumab, 300 mg (245) | 65.3% | 81.6% | 59.2% | 28.6% |
| Secukinumab, 150 mg (245) | 51.2% | 71.6% | 39.1% | 12.8% | |||
| Placebo (248) | 2.4% | 4.5% | 1.2% | 0.8% | |||
| FIXTURE | 2014 | 1,306 | Secukinumab, 300 mg (327) | 62.5% | 77.1% | 54.2% | 24.1% |
| Secukinumab, 150 mg (327) | 51.1% | 67.0% | 41.9% | 14.4% | |||
| Etanercept (326) | 27.2% | 4.0% | 20.7% | 4.3% | |||
| Placebo (326) | 2.8% | 4.9% | 1.5% | 0.0% | |||
| CLEAR | 2015 | 676 | Secukinumab, 300 mg (337) | 80.8% | 91.0% | 72.8% | 38.9% |
| Ustekinumab (339) | 65.1% | 79.1% | 53.4% | 25.7% | |||
| SCULPTURE | 2015 | 966 | Secukinumab, 300 mg (484) | – | 90.1% | – | – |
| Secukinumab, 150 mg (482) | – | 84.4% | – | – | |||
| FEATURE | 2014 | 177 | Secukinumab, 300 mg (59) | 69.0% | 75.9% | 60.3% | 43.1% |
| Secukinumab, 150 mg (59) | 52.5% | 69.5% | 45.8% | 8.5% | |||
| Placebo (59) | 0.0% | 0.0% | 0.0% | 0.0% | |||
| JUNCTURE | 2014 | 182 | Secukinumab, 300 mg (60) | 73.3% | 86.7% | 55.0% | 26.7% |
| Secukinumab, 150 mg (61) | 53.3% | 71.7% | 40.0% | 16.7% | |||
| Placebo (61) | 0.0% | 3.3% | 0.0% | 0.0% | |||
Notes:
With ≥2-grade improvement from baseline; PASI 100, 100% improvement in PASI from baseline; PASI 75, ≥75% improvement in PASI from baseline; PASI 90, ≥90% improvement in PASI from baseline.
Abbreviations: IGA, Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index.
Clinical efficacy of biologic treatments for plaque psoriasis in pivotal Phase III trials
| Drug/Trial | Dose | Frequency | Contraindications | PASI 75 | PASI 90 | PASI 100 |
|---|---|---|---|---|---|---|
|
| ||||||
| Ustekinumab | 45 mg | 12 weeks | None | |||
| PHOENIX 1 | 67% | 42% | 13% | |||
| PHOENIX 2 | 17% | 42% | 18% | |||
| ACCEPT | 68% | 36% | 16% | |||
| Guselkumab | 100 mg | 8 weeks | None | |||
| VOYAGE 1 | 91% | 73% | 37% | |||
| VOYAGE II | 86% | 70% | 34% | |||
| Tildrakizumab | 100 mg | 12 weeks | None | |||
| RESURFACE 1 | 64% | 35% | 14% | |||
| RESURFACE 2 | 61% | 39% | 12% | |||
| Risankixumab | 150 mg | 12 weeks | None | |||
| ultIMMa-1 | – | 75% | 36% | |||
| ultIMMa-2 | – | 75% | 51% | |||
| IMMvent | – | 72% | 40% | |||
| IMMhance | 89% | 73% | 47% | |||
| Brodalumab | 210 mg | 2 weeks | Crohn’s disease | |||
| AMAGINE-1 | 83% | 70% | 42% | |||
| AMAGINE-2 | 86% | – | 44% | |||
| AMAG1NE-3 | 85% | – | 37% | |||
| Secukinumab | 300 mg | 4 weeks | Hypersensitivity to drug | |||
| ERASURE | 82% | 59% | 29% | |||
| FIXTURE | 77% | 54% | 24% | |||
| Ixekixumab | 80 mg | 4 weeks | Hypersensitivity to drug | |||
| UNCOVER-1 | 83% | 65% | 34% | |||
| UNCOVER-2 | 78% | 60% | 31% | |||
| UNCOVER-3 | 84% | 65% | 35% | |||
Notes: Adapted from Yang et al (2018).46
Measured at 12 weeks, except guselkumab and risankizumab which were measured at 16 weeks.
Not currently approved for the treatment of plaque psoriasis. PASI 100, ≥100% improvement in PASI from baseline; PASI 75, ≥75% improvement in PASI from baseline; PASI 90, ≥90% improvement in PASI from baseline.
Abbreviation: PASI, Psoriasis Area and Severity Index.
Summary of key Phase III clinical trial results of secukinumab for the treatment of psoriatic arthritis
| Trial | Year | n | Treatment (n) | ACR20 | ACR50 | Change in HAQ-DI | Change in DAS-CRP | Change in SF-36 PCS |
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| FUTURE-1 | 2015 | 606 | Secukinumab, 150 mg (202) | 50.0% | 34.7% | −0.40 | –1.62 | 5.91 |
| Secukinumab, 75 mg (202 | 50.5% | 30.7% | −0.41 | –1.67 | 5.41 | |||
| Placebo (202) | 17.3% | 7.4% | −0.17 | –0.77 | 1.82 | |||
| FUTURE-2 | 2015 | 397 | Secukinumab, 300 mg (100) | 54.0% | 35.0% | –0.56 | –1.61 | 7.25 |
| Secukinumab, 150 mg (100) | 51.0% | 35.0% | –0.48 | –1.58 | 6.39 | |||
| Secukinumab, 75 mg (99) | 29.3% | 18.2% | –0.32 | –1.12 | 4.38 | |||
| Placebo (98) | 15.3% | 7.1% | –0.31 | –0.96 | 1.95 | |||
| FUTURE-3 | 2018 | 416 | Secukinumab, 300 mg (139) | 48.2% | 34.5% | –0.38 | –1.56 | 6.46 |
| Secukinumab, 150 mg (138) | 42.0% | 18.8% | –0.27 | –1.24 | 3.42 | |||
| Placebo (137) | 16.1% | 8.8% | –0.17 | –0.64 | 2.94 | |||
| FUTURE-5 | 2018 | 996 | Secukinumab, 300 mg (222) | 62.6% | 39.6% | –0.55 | –1.49 | – |
| Secukinumab, 150 mg with loading dose (220) | 55.5% | 35.9% | –0.44 | –1.29 | – | |||
| Secukinumab 150 mg without loading dose (222) | 59.5% | 32.0% | –0.45 | –1.29 | – | |||
| Placebo (332) | 27.4% | 8.1% | –0.21 | –0.63 | – | |||
Notes: Endpoints for all trials were measured at week 24, except for FUTURE-5 which were measured at week 16. ACR20, ≥20% improvement in ACR from baseline; ACR50, ≥50% improvement in ACR from baseline.
Abbreviations: ACR, American College of Rheumatology score; DAS-CRP, 28-joint Disease Activity Score on the basis of levels of C-reactive protein; HAQ-DI, Health Assessment Questionnaire-Disability Index; SF-36 PCS, Short Form 36-Item Physical Component Summary Score of the Medical Outcomes Survey.