Why carry out this study?
|
Psoriasis is a chronic inflammatory multisystem disease which has a substantial negative impact on the patients’ quality of life and physical and psychologic functioning. Thus, it represents a major economic burden to health systems owing to the disease’s chronicity, high prevalence, and disabling effect |
The use of biologic therapy has revolutionized the management of moderate-to-severe psoriasis offering healthcare providers and patients with a multitude of highly effective and tolerable treatment options. Nevertheless, head-to-head comparisons between the different biologic treatments in psoriasis are limited. This subsequently leads to uncertainty about their comparative efficacy and limits the clinicians’ and patients’ ability to make informed decisions about treatment choices. Therefore, we sought to conduct a network meta-analysis (NMA) which allows for comparison between multiple treatments that are not directly compared in a randomized controlled trial (RCT) and produces estimates of treatment effects and rankings that may be used in decision-making |
What did the study ask?/What was the hypothesis of the study?
|
The current study conducted a systematic literature review and an NMA to compare the short-term efficacy at 10–16 weeks (according to the Psoriasis Area and Severity Index [PASI]) among the approved biologic systemic therapies for moderate-to-severe psoriasis |
What was learned from the study?
What were the study outcomes/conclusions? (data)
|
The biologics were associated with better probability of achieving all PASI response levels compared with non-biologics and placebo. All biologics except etanercept had > 80% probability of achieving PASI50. Interleukin inhibitors (risankizumab 150 mg, ixekizumab 80 mg, brodalumab 210 mg, secukinumab 300 mg, and guselkumab 100 mg) were the best-performing treatments for achieving all levels of short-term PASI (50, 75, 90, and 100). Certolizumab pegol 400 mg and infliximab 5 mg/kg performed the best among the tumor necrosis factor-α inhibitors |
Introduction
Methods
SLR Overview
Drugs | Dosages |
---|---|
Systemic biologics | |
Adalimumab | 40 mg EOW |
Brodalumab | 210 mg Q2W |
Certolizumab pegol | 400 mg or 200 mg Q2W |
Etanercept | 50 mg or 25 mg Q2W |
Guselkumab | 100 mg Q8W |
Infliximab | 5 mg/kg Q8W |
Ixekizumab | 80 mg Q4W |
Risankizumab | 150 mg Q12W |
Secukinumab | 150 mg or 300 mg Q4W |
Tildrakizumab | 100 mg or 200 mg Q12W |
Ustekinumab | 45 mg or 90 mg Q12Wa |
Systemic non-biologics | |
Acitretin | 0.4 mg/kg |
Apremilast | 30 mg BID |
Cyclosporine | 2.5–5 mg/kg/day |
Dimethyl fumarate | 720 mg |
Methotrexate | 7.5–15 mg |
Study Characteristics and NMA Assumptions
PICOS | Inclusion for analysis | Exclusion criteria |
---|---|---|
Population | Patients with moderate-to-severe PsO with or without comorbid PsA Studies providing subgroup data for those moderate-to-severe plaque PsO | Studies in patients primarily with PsA or with a treatment focus for PsA |
Intervention/Comparator | Any protocol-approved intervention and dose | Studies in biosimilar compounds |
Outcomes | Any combination of PASI 50, 75, 90 and/or 100 presented as discrete/categorical outcomes | Mean change in PASI score |
Time points | 10–16 weeks [99] | < 10 weeks or > 16 weeks |
Study design | Randomized controlled trials | Open label extension or follow-up studies |
Pre-defined sensitivity analysis | Previous systemic biologic treatment | Other subgroups (i.e., patient demographics, comorbid conditions) |
Other restrictions | Randomized controlled trials with sample size > 30 patients |
Statistical Analysis
Results
SLR Search Results
Study and Patient Characteristics
Study (phase) | Primary end point (weeks) | Severity definition | Intervention(s) and comparators | Age in years: mean (SD) | Male (%) | PsA (%) | Disease duration (years) | Percent with prior therapy biologic/non-biologic |
---|---|---|---|---|---|---|---|---|
Griffiths (2010) [49] ACCEPT (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Etanercept 50 mg BIW | 45.7 (13.4) | 70.9 | 27.4 | 18.8 | 11.8/NR |
Ustekinumab 45 mg Q12W | 45.1 (12.6) | 63.6 | 29.7 | 18.9 | 12.4/NR | |||
Ustekinumab 90 mg Q12W | 44.8 (12.3) | 67.4 | 27.4 | 18.7 | 10.4/NR | |||
Papp (2016) [86] AMAGINE 1 (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Brodalumab 210 mg Q2W | 46.0 (12) | 73.0 | 26.0 | 20.0 | 46.0/NR |
Placebo | 47.0 (13) | 73.0 | 29.0 | 21.0 | 45.0/NR | |||
Lebwohl (2015) [54] AMAGINE 2 [100] (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Ustekinumab 45 or 90 mg Q12W | 45.0 (13) | 68.0 | 17.0 | 19.0 | 28.0/NR |
Brodalumab 210 mg Q2W | 45.0 (13) | 69.0 | 19.0 | 19.0 | 29.0/NR | |||
Placebo | 44.0 (13) | 71.0 | 17.0 | 18.0 | 29.0/NR | |||
Lebwohl (2017) [54] AMAGINE 3 [100] (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Placebo | 44.0 (13) | 66.0 | 19.0 | 18.0 | 24.0/NR |
Ustekinumab 45 or 90 mg Q12W | 45.0 (13) | 68.0 | 20.0 | 18.0 | 24.0/NR | |||
Brodalumab 210 mg Q2W | 45.0 (13) | 69.0 | 20.0 | 18.0 | 25.0/NR | |||
Antiga (2010) [101] (NR) | 12 | PASI ≥ 10 BSA ≥ 10% | Etanercept 50 mg BIW | 31.0–63.0 | 40.0 | NR | NR | NR/NR |
Acitretin 0.4 mg/kg/day | 27.0–58.0 | 50.0 | NR | NR | NR/NR | |||
Asahina (2010) [26] (Phase II/III) | 24 | PASI ≥ 12 BSA ≥ 10% | Adalimumab 80 mg Q2W | 44.2 (14.3) | 81.4 | 18.6 – 55.8 | 14.0 | 0*/NR |
Placebo | 43.9 (10.8) | 89.1 | 17.4 – 54.3 | 15.5 | 0*/NR | |||
Bachelez (2015) [27] (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% | Etanercept 50 mg BIW | 42.0 | 70.0 | 21.0 | 18.0 | 11.0/NR |
Placebo | 46.0 | 66.0 | 24.0 | 17.0 | 11.0/NR | |||
Bagel (2012) [102] (NR) | 12 | PASI ≥ 10 BSA ≥ 10% | Etanercept 50 mg BIW | Median (range): 39.0 (18.0–71.0) | 53.2 | NR | 17.5 | NR |
Placebo | Median (range): 42.0 (18.0–70.0) | 58.1 | NR | 11.9 | NR | |||
Mrowietz (2017) [61] BRIDGE (Phase III) | 16 | PASI ≥ 10 BSA ≥ 10% PGA ≥ 3 | DMF up to 720 mg | 44.0 (15.2) | 62.4 | NR | NR | 2.9*/NR |
Placebo | 44.0 (14.3) | 67.9 | NR | NR | 2.2*/NR | |||
Cai (2017) [32] (Phase III) | 12 | NR | Adalimumab 40 mg Q2W | 43.1 (11.9) | 75.1 | 12.7 | 14.8 | 0/NR |
Placebo | 43.8 (12.5) | 66.7 | 11.5 | 15.8 | 0/NR | |||
Caproni (2009) [33] (NR) | 12 | PASI ≥ 10 BSA ≥ 10% | Etanercept 50 mg BIW | 28.0–67.0 | 43.3 | NR | NR | NR/NR |
Acitretin 0.4 mg/kg/day | 310.–65.0 | 36.7 | NR | NR | NR/NR | |||
von Stebut (2019) [79] CARIMA (Phase III) | 12 | PASI ≥ 10 | Secukinumab 150 mg | 46.0 (14.4) | 57.4 | 27.8 | 20.8 | 31.1/89.6 |
Secukinumab 300 mg | 44.2 (12.9) | 77.1 | 25.0 | 20.6 | 37.0/85.2 | |||
Placebo to Secukinumab 150 mg a | 46.8 (13.1) | 69.6 | 17.4 | 20.3 | 39.1/69.6 | |||
Placebo Secukinumab 300 mg
a | 43.7 (11.4) | 69.2 | 15.4 | 18.9 | 30.8/92.3 | |||
(Phase III) | 16 | PASI ≥ 10 BSA ≥ 10% | Adalimumab 40 mg Q2W | 42.9 (12.6) | 64.8 | 21.3 | 17.9 | 0*/NR |
Methotrexate 7.5 mg–25 mg QW | 41.6 (12.0) | 66.4 | 17.3 | 18.9 | 0*/NR | |||
Placebo | 40.7 (11.4) | 660 | 20.8 | 18.8 | 0*/NR | |||
Chaudhari (2001)[103] (NR) | 10 | BSA ≥ 5% | Infliximab 5 mg/kg Q4W | 51.0 (14.0) | 63.6 | NR | NR | 0*/NR |
Placebo | 45.0 (12.0) | 72.7 | NR | NR | 0*/NR | |||
Lebwohl (2018) [53] CIMPACT (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Certolizumab pegol 200 mg Q2W | 46.7 (13.5) | 68.5 | 16.4 | 19.5 | 26.7/NR |
Certolizumab pegol 400 mg Q2W | 45.4 (12.4) | 64.1 | 14.4 | 17.8 | 28.7/NR | |||
Etanercept 50 mg BIW | 44.6 (14.1) | 74.7 | 15.9 | 17.4 | 30.0/NR | |||
Placebo | 46.5 (12.5) | 59.6 | 21.2 | 18.9 | 19.3/NR | |||
Gottlieb (2018) [44] CIMPASI-I (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Certolizumab pegol 200 mg Q2W | 44.5 (13.1) | 70.5 | 10.5 | 16.6 | 31.6/69.5 |
Certolizumab pegol 400 mg Q2W | 43.6 (12.1) | 68.2 | 17.0 | 18.4 | 33.0/69.3 | |||
Placebo | 47.9 (12.8) | 68.6 | 7.8 | 18.5 | 29.4/70.6 | |||
Gottlieb (2018) [44] CIMPASI-II (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Certolizumab pegol 200 mg Q2W | 46.7 (13.3) | 63.7 | 24.2 | 18.8 | 35.2/71.4 |
Certolizumab pegol 400 mg Q2W | 46.4 (13.5) | 49.4 | 29.9 | 18.6 | 34.5/72.4 | |||
Placebo | 43.3 (14.5) | 53.1 | 18.4 | 15.4 | 28.6/73.5 | |||
Bagel (2018) [28] CLARITY (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% mIGA 2011 ≥ 3 | Secukinumab 300 mg Q4W | 45.4 (14.1) | 64.7 | NR | 16.8 | 20.0/NR |
Ustekinumab 45 or 90 mg Q12W | 45.3 (14.2) | 68.1 | NR | 17.3 | 23.6/NR | |||
Thaci (2015) [75] CLEAR (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% mIGA ≥ 3 | Secukinumab 300 mg Q4W | 45.2 (14) | 68.0 | 20.5 | 19.7 | 14.2/NR |
Ustekinumab 45 or 90 mg Q12W | 44.6 (13.7) | 74.3 | 15.9 | 16.1 | 13.0/NR | |||
Reich (2019) [104] ECLIPSE (Phase III) | 12 | NR | Guselkumab 100 mg Q8W | NR | NR | NR | NR | NR/NR |
Secukinumab 300 mg Q4W | NR | NR | NR | NR | NR/NR | |||
Guselkumab 100 mg Q8W | NR | NR | NR | NR | NR/NR | |||
Secukinumab 300 mg Q4W | NR | NR | NR | NR | NR/NR | |||
Langley (2014) [52] ERASURE (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Secukinumab 300 mg Q4W | 44.9 (13.5) | 69.0 | 23.3 | 17.4 | 28.6/NR |
Secukinumab 150 mg Q4W | 44.9 (13.3) | 68.6 | 18.8 | 17.5 | 29.8/NR | |||
Placebo | 45.4 (12.6) | 69.4 | 27.4 | 17.3 | 29.4/NR | |||
Langley (2014) [52] FIXTURE (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Secukinumab 300 mg Q4W | 44.5 (13.2) | 68.5 | 15.3 | 15.8 | 11.6/NR |
Secukinumab 150 mg Q4W | 45.4 (12.9) | 72.2 | 15.0 | 17.3 | 13.8/NR | |||
Etanercept 50 mg BIW | 43.8 (13.0) | 71.2 | 13.5 | 16.4 | 13.8/NR | |||
Placebo | 44.1 (12.6) | 72.7 | 15.0 | 16.6 | 10.7/NR | |||
Papp (2015) [83] ESTEEM 1 (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Apremilast 30 mg BID | 45.8 (13.1) | 67.0 | NR | 19.8 | 28.8/NR |
Placebo | 46.5 (12.7) | 69.0 | NR | 18.7 | 28.4/NR | |||
Paul (2015) [66] ESTEEM 2 (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Apremilast 30 mg BID | 45.3 (13.1) | 64.0 | NR | 17.9 | 33.6/NR |
Placebo | 45.7 (13.4) | 73.0 | NR | 18.7 | 32.1/NR | |||
Reich (2005) [67] EXPRESS (Phase III) | 10 | PASI ≥ 12 BSA ≥ 10% | Infliximab 5 mg/kg Q8W | 42.6 (11.7) | 69.0 | 31.0 | 19.1 | 0/0 |
Placebo | 43.8 (12.6) | 79.0 | 29.0 | 17.3 | 0/0 | |||
EXPRESS II [58] (Phase III) | 14 | PASI ≥ 12 BSA ≥ 10% | Infliximab 5 mg/kg Q8W | 44.5 (13) | 65.0 | 28.3 | 19.1 | 14.3/NR |
Placebo | 44.4 (12.5) | 69.2 | 26.0 | 17.8 | 13.0/NR | |||
FEATURE (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% mIGA 2011 ≥ 3 | Secukinumab 300 mg Q4W | 45.1 (12.6) | 64.4 | NR | 18.0 | 39.0/NR |
Secukinumab 150 mg Q4W | 46 (15.1) | 67.8 | NR | 20.4 | 47.5/NR | |||
Placebo | 46.5 (14.1) | 66.1 | NR | 20.2 | 44.1/NR | |||
Flystrom (2008) [35] (NR) | 12 | NR | Methotrexate 7.5–15 mg QW | 48.0 | 75.7 | NR | NR | 0/NR |
Ciclosporin 3–5 mg/kg QD | 45.0 | 87.1 | NR | NR | 0/NR | |||
Gisondi (2008) [37] (NR) | 24 | NR | Etanercept 25 mg BIW | 55.3 (10.9) | 54.6 | NR | 23.5 | 0/NR |
Acitretin 0.4 mg/kg QD | 55 (11.3) | 60.0 | NR | 18.8 | 0/NR | |||
Goldminz (2015) [105] (NR) | 16 | PGA ≥ 3 | Adalimumab 40 mg Q2W | 50.5 (NR) | 73.3 | 13.3 | 17.3 | 0/40.0 |
Methotrexate 7.5–25 mg/week | 50.3 (NR) | 86.7 | 20.0 | 21.5 | 0/26.7 | |||
Gottlieb (2003) [47] (Phase II) | 24 | BSA ≥ 10%, active, stable plaque | Etanercept 25 mg BIW | 48.2 | 58.0 | 28.0 | 23.0 | 0/NR |
Placebo | 46.5 | 67.0 | 35.0 | 20.0 | 0/NR | |||
Gottlieb (2011)
[46] M10-114 (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Placebo | 44.0 (13.6) | 69.1 | 20.6 | 19.1 | 14.7/NR |
Etanercept 50 mg BIW | 43.1 (12.5) | 69.5 | 22.7 | 17.0 | 14.2/NR | |||
Heydendael (2003) [50] (NR) | 16 | PASI ≥ 8 | Methotrexate 15 mg QD for 4 W then up to 22.5 mg QD | 41.6 (13.0) | 65.1 | 7.0 | NR | 0*/NR |
Cyclosporine 3 to 5 mg/kg/day | 38.3 (12.4) | 69.0 | 2.4 | NR | 0*/NR | |||
Igarashi (2012) [51] (Phase II/III) | 12 | PASI ≥ 12, BSA ≥ 10% | Ustekinumab 45 mg Q12W | Median: 45.0 | 82.8 | 9.4 | 15.8 | 1.6/0 |
Ustekinumab 90 mg Q12W | Median: 44.0 | 75.8 | 11.3 | 17.3 | 0/0 | |||
Placebo | Median: 49.0 | 83.9 | 3.1 | 16.0 | 0/0 | |||
Reich (2017) [106] IXORA-S (Phase III) | 12 | PASI ≥ 10 | Ustekinumab 45 mg or 90 mg Q12W | 44.0 (13.3) | 67.5 | NR | 18.2 | 15.1/NR |
Ixekizumab 80 mg Q2W | 42.7 (12.7) | 66.2 | NR | 18.0 | 13.2/NR | |||
Paul (2015) [66] JUNCTURE (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Secukinumab 300 mg W1, 2, 3, then Q4W after W4 | 46.6 (14.2) | 76.7 | 23.3 | 21.0 | 25.0/NR |
Secukinumab 150 mg W1, 2, 3, then Q4W after W4 | 43.9 (14.4) | 67.2 | 26.2 | 20.6 | 24.6/NR | |||
Placebo | 43.7 (12.7) | 62.3 | 19.7 | 19.9 | 21.3/NR | |||
Leonardi (2003) [56] (Phase III) | 12 | PASI ≥ 10, BSA ≥ 10% | Etanercept 25 mg BIW | 45.4 (1) | 67.0 | NR | 18.5 | 0*/NR |
Etanercept 50 mg BIW | 44.8 (0.8) | 65.0 | NR | 18.6 | 0*/NR | |||
Placebo | 45.6 (1.0) | 63.0 | NR | 18.4 | 0*/NR | |||
Reich (2017) [71] LIBERATE (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Etanercept 50 mg QWb | 47.0 (14.1) | 59.0 | NR | 18.1 | 0/NR |
Placebo | 43.4
(14.9) | 70.2 | NR | 16.6 | 0/NR | |||
Apremilast 30 mg BID | 46 (13.6) | 59.0 | NR | 19.7 | 0/NR | |||
Gordon (2006) [42] M02-528 (Phase II) | 12 | BSA ≥ 5% PsO ≥ 1 year | Adalimumab 40 mg EOW | 46.0 | 71.0 | 33.0 | 21.0 | 0*/NR |
Placebo | 43.0 | 65.0 | 31.0 | 19.0 | 0*/NR | |||
Meffert (1997) [57] (NR) | 10 | PASI 8–25 | Cyclosporin A 2.5 mg/kg/day | NR | NR | NR | NR | 0*/NR |
Placebo | NR | NR | NR | NR | 0*/NR | |||
Nakagawa (2016) [62] (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% | Brodalumab 210 mg Q2W | 46.4 (11.8) | 78.4 | 13.5 | 15.0 | 13.5/NR |
Placebo | 46.6 (10.8) | 71.1 | 18.4 | 16.9 | 7.9/NR | |||
Ohtsuki (2018) [63] (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% IGA ≥ 3 | Guselkumab 100 mg Q8W | 47.8 (11.1) | 74.6 | 15.9 | 14.4 | 17.5/NR |
Placebo | 48.3 (10.6) | 84.4 | 15.6 | 13.7 | 15.6/NR | |||
Ohtsuki (2017) [64] (Phase II) | 16 | PASI ≥ 12 BSA ≥ 10% | Apremilast 30 mg BID | 51.7 (12.7) | 83.5 | NR | 13.9 | 2.4/NR |
Placebo | 48.3 (12.0) | 73.8 | NR | 12.4 | 4.8/NR | |||
Papp (2005) [87] (NR) | 12 | PASI ≥ 10 BSA ≥ 10% | Etanercept 50 mg BIW | 44.5 | 67.0 | 26.0 | 18.1 | 0*/NR |
Etanercept 25 mg BIW | 46.0 | 65.0 | 28.0 | 21.5 | 0*/NR | |||
Placebo | 44.0 | 64.0 | 26.0 | 17.5 | 0*/NR | |||
(Phase III) | 12 | NR | Brodalumab 210 mg Q2W | 42.1 (12.2) | 62.0 | 30.0 | 17.1 | 0/NR |
Placebo | 41.8 (14.4) | 58.0 | 18.0 | 18.3 | 0/NR | |||
Papp (2012b) [81] (Phase II) | 24 | PASI ≥ 12 BSA ≥ 10% | Apremilast 30 mg BID | 44.1 (14.7) | 57.0 | 24.0 | 19.2 | NR/NR |
Placebo | 44.1 (13.7) | 60.0 | 19.0 | 19.6 | NR/NR | |||
Papp (2015) [83] (Phase II) | 16 | PASI ≥ 12 BSA ≥ 10% | Tildrakizumab 100 mg Q12W | 45.5 (12.8) | 85.0 | 17.0 | NR | 0*/NR |
Tildrakizumab 200 mg Q12W | 43.2 (12.6) | 76.0 | 17.0 | NR | 0*/NR | |||
Placebo | 45.9 (11.7) | 83.0 | 24.0 | NR | NR/NR | |||
Menter (2008) [59] PHOENIX 1 (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% | Ustekinumab 45 mg Q12W | 44.8 (12.5) | 68.6 | 29.0 | 19.7 | 52.5/NR |
Ustekinumab 90 mg Q12W | 46.2 (11.3) | 67.6 | 36.7 | 19.6 | 50.8/NR | |||
Placebo | 44.8 (11.3) | 71.8 | 35.3 | 20.4 | 50.2/NR | |||
Leonardi (2008) [55] PHOENIX 2 (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% | Ustekinumab 45 mg Q12W | 45.1 (12.1) | 69.2 | 26.2 | 11.7 | 38.4/NR |
Ustekinumab 90 mg Q12W | 46.6 (12.1) | 66.7 | 22.9 | 12.3 | 36.5/NR | |||
Placebo | 47.0 (12.5) | 69.0 | 25.6 | 12.2 | 38.8/NR | |||
de Vries (2017) [34] PIECE (NR) | 24 | PASI ≥ 10 and/or BSA ≥ 10 and/or PASI ≥ 8 Skindex-29 score ≥ 35 | Etanercept 50 mg BIW | 42.4 (13.2) | 56.0 | 13.0 | 17.9 | 8.0*/NR |
Infliximab 5 mg/kg Q8W | 45.9 (13.9) | 72.0 | 8.0 | 21.5 | 9.0*/NR | |||
Reich (2012) [69] (Phase II) | 12 | PASI ≥ 12 BSA ≥ 10% | CZP 200 mg Q2W | 43.3 (10.1) | 75.0 | NR | 21.0 | 22.0/NR |
CZP 400 mg Q2W | 43.6 (12.4) | 72.0 | NR | 19.6 | 24.0/NR | |||
Placebo | 43.3 (12.8) | 63.0 | NR | 19.7 | 24.0/NR | |||
Reich (2020) [107] (Phase III) | 24 | NR | Ixekizumab 160 mg then 80 mg | NR | NR | NR | NR | 0/0 |
Methotrexate 7.5–25 mg/week | NR | NR | NR | NR | 0/0 | |||
RESTORE 1 [29] (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% | Infliximab 5 mg/kg Q8W | 44.1 | 67.0 | NR | 18.8 | 8.3/61.1 |
Methotrexate 15 mg QW | 41.9 | 69.0 | NR | 17.0 | 8.4/64.7 | |||
Barker (2011) [71] RESURFACE 1 (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Tildrakizumab 200 mg Q12W | 46.9 (13.2) | 73.0 | NR | NR | 23.0/NR |
Tildrakizumab 100 mg Q12W | 46.4 (13.3) | 67.0 | NR | NR | 23.0/NR | |||
Placebo | 47.9 (13.5) | 65.0 | NR | NR | 23.0/NR | |||
Reich (2017 [71] RESURFACE 2 (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Tildrakizumab 200 mg Q12W | 44.6 (13.6) | 72.0 | NR | NR | 12.0/NR |
Tildrakizumab 100 mg Q12W | 44.6 (13.6) | 72.0 | NR | NR | 13.0/NR | |||
Etanercept 50 mg Q2W | 45.8 (14) | 71.0 | NR | NR | 12.0/NR | |||
Placebo | 46.4 (12.2) | 72.0 | NR | NR | 13.0/NR | |||
REVEAL (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% PGA ≥ moderate | Adalimumab 40 mg Q2W | 44.1 (13.2) | 67.1 | 27.5 | 18.1 | 11.9/NR |
Placebo | 45.4 (13.4) | 64.6 | 28.4 | 18.4 | 13.3/NR | |||
Rich (2013) [109] (Phase II) | 12 | NR | Secukinumab 150 mg Q4W | 44.2 (13.0) | 75.4 | 32.6 | 16.9 | 29.7/NR |
Placebo | 44.2 (12.6) | 65.7 | 17.9 | 15.4 | 25.4/NR | |||
SPIRIT [45] (NR) | 10 | PASI ≥ 12 BSA ≥ 10% | Infliximab 5 mg/kg Q4W | Median (IQR): 44.0 (34.0 to 53.0) | 73.7 | 29.3 | NR | 33.3/NR |
Placebo | Median (IQR): 45.0 (30.0 to 52.0) | 60.8 | 33.3 | NR | 31.4/NR | |||
Torii (2010) [76] (Phase III) | 10 | PASI ≥ 12 BSA ≥ 10% | Infliximab 5 mg/kg Q8W | 46.9 (13.0) | 62.9 | 28.6 | 14.2 | 0/NR |
Placebo | 43.3 (12.3) | 73.7 | 36.8 | 11.1 | 0/NR | |||
Reich (2019) [72] TRANSFIGURE (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% NAPSI ≥ 16 at least 4 fingernails | Secukinumab 300 mg Q4W | 45.1 (12.9) | 80 | 26 | 18 | 24/NR |
Secukinumab 150 mg Q4W | 43.5 (10.9) | 82 | 24 | 20 | 22/NR | |||
Placebo | 43.6 (11.2) | 80 | 28 | 17.4 | 23/NR | |||
Tyring (2006) [77] (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% | Etanercept 50 mg BIW | 45.8 (12.8) | 65.0 | 35.0 | 20.1 | 0*/NR |
Placebo | 45.6 (12.1) | 70.0 | 33.0 | 19.7 | 0*/NR | |||
Gordon (2018) [38] UltlMMa 1 (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% sPGA ≥ 3 | Risankizumab 150 mg Q12W | 48.3 (13.4) | 70.0 | 28.0 | NR | 34.0/NR |
Ustekinumab 45 or 90 mg Q12W | 46.5 (13.4) | 70.0 | 23.0 | NR | 30.0/NR | |||
Placebo | 49.3 (13.6) | 77.0 | 35.0 | NR | 39.0/NR | |||
Gordon (2018) [38] UltlMMa 2 (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% sPGA ≥ 3 | Risankizumab 150 mg Q12W | 46.2 (13.7) | 69.0 | 25.0 | NR | 40.0/NR |
Ustekinumab 45 or 90 mg Q12W | 48.6 (14.8) | 67.0 | 27.0 | NR | 43.0/NR | |||
Placebo | 46.3 (13.3) | 68.0 | 33.0 | NR | 43.0/NR | |||
Gordon (2016) [40] UNCOVER 1 (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% sPGA ≥ 3 | Ixekizumab 80 mg Q4W | 46.0 (13.0) | 67.0 | NR | 19.0 | 38.9/NR |
Placebo | 46.0 (13.0) | 70.0 | NR | 20.0 | 42.0/NR | |||
Gordon (2016) [40]; Gottlieb (2017) [110]; Griffiths (2015 [48]; Kemeny (2019) [111]; Papp (2018) [85] (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% sPGA ≥ 3 | Ixekizumab 80 mg Q4W | 45.0 (14.0) | 70.0 | NR | 19.0 | 24.5/NR |
Etanercept 50 mg BIW | 45.0 (13.0) | 66.0 | NR | 19.0 | 21.2/NR | |||
Placebo | 45.0 (12.0) | 71.0 | NR | 19.0 | 25.6/NR | |||
Gordon (2016) [40] UNCOVER 3 (Phase III) | 12 | PASI ≥ 12 BSA ≥ 10% sPGA ≥ 3 | Ixekizumab 80 mg Q4W | 46.0 (13.0) | 67.0 | NR | 18.0 | 15.0/NR |
Etanercept 50 mg BIW | 46.0 (14.0) | 70.0 | NR | 18.0 | 15.7/NR | |||
Placebo | 46.0 (12.0) | 71.0 | NR | 18.0 | 17.1/NR | |||
Stein (2018) UNVEIL [74] (Phase IV) | 16 | BSA 5%–10% sPGA = 3 | Apremilast 30 mg BID | 48.6 (15.4) | 50.0 | NR | 17.5 | 0/NR |
Placebo | 51.1 (13.7) | 56.2 | NR | 13.9 | 0/NR | |||
Van de Kerkhof (2008) [78] (Phase III) | 12 | PASI ≥ 10 BSA ≥ 10% | Etanercept 50 mg QW | 45.9 (12.8) | 61.5 | 15.6 | 19.3 | 0/NR |
Placebo | 43.6 (12.6) | 54.4 | 10.9 | 17.3 | 0/NR | |||
Gefland (2018) [36] VIP (Phase IV) | 12 | PASI ≥ 12 BSA ≥ 10 | Adalimumab 40 mg Q2W | 44.1 (14.0) | 72.7 | 12.1 | 14.9 | NR/NR |
Placebo | 44.3 (14.5) | 64.5 | 6.5 | 19.3 | NR/NR | |||
Blauvelt (2017) [30] VOYAGE 1 (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% IGA ≥ 3 | Guselkumab 100 mg Q8W | 43.9 (12.7) | 72.9 | 19.5 | 17.9 | 21.6/NR |
Adalimumab 40 mg Q2W | 42.9 (12.6) | 74.6 | 18.6 | 17.0 | 21.0/NR | |||
Placebo | 44.9 (12.9) | 68.4 | 17.2 | 17.6 | 19.5/NR | |||
Reich (2017) [71] VOYAGE 2 (Phase III) | 16 | PASI ≥ 12 BSA ≥ 10% IGA ≥ 3 | Guselkumab 100 mg Q8W | 43.7 (12.2) | 70.4 | 17.9 | 17.9 | 20.4/NR |
Adalimumab 40 mg Q2W | 43.2 (11.9) | 68.5 | 17.7 | 17.6 | 19.8/NR | |||
Placebo | 43.3 (12.4) | 69.8 | 18.5 | 17.9 | 21.8/NR | |||
Gordon (2015) X-PLORE [41] (Phase II) | 16 | PASI ≥ 12 BSA ≥ 10% PGA ≥ 3 | Guselkumab 100 mg Q8W | 44.0 | 72.0 | 25.0 | 18.5 | NR/NR |
Adalimumab 40 mg Q2W | 50.0 | 70.0 | 26.0 | 19.3 | 60.0/NR | |||
Placebo | 46.5 | 67.0 | 29.0 | 18.0 | 36.0/NR | |||
Yang (2012) [80] (Phase III) | 10 | PASI ≥ 12 BSA ≥ 10% | Infliximab 5 mg/kg Q8W | 39.4 (12.3) | 71.4 | NR | 16.0 | NR/100.0 |
Placebo | 40.1 (11.1) | 77.8 | NR | 16.0 | NR/NR |
NMA Results
Model | \({\beta }_{\mathrm{BL}} (95\mathrm{\% CrI})\) | \({\widehat{\sigma }}_{z} (95\mathrm{\% CrI})\) | \(\widehat{\tau } (95\mathrm{\% CrI})\) | \(\overline{D }\)* | DIC |
---|---|---|---|---|---|
REZ, adjusted, FE | −0.551 (−0.667, −0.411) | 0.078 (0.057, 0.106) | – | 661.0 | 836.8 |
REZ, adjusted, RE | −0.690 (−0.861, −0.533) | 0.078 (0.056, 0.106) | 0.103 (0.066, 0.148) | 609.8 | 832.8 |
REZ, unadjusted, FE | – | 0.080 (0.059, 0.110) | – | 637.9 | 785.5 |
REZ, unadjusted, RE | – | 0.080 (0.059, 0.110) | 0.103 (0.045, 0.160) | 604.6 | 813.4 |
Standard, adjusted, FE | −0.575 (−0.689, −0.439) | – | – | 793.5 | 919.0 |
Standard, adjusted, RE | −0.715 (−0.898, −0.561) | – | 0.104 (0.068, 0.149) | 738.6 | 914.9 |
Standard, unadjusted, FE | – | – | – | 773.6 | 870.7 |
Standard, unadjusted, RE | – | – | 0.113 (0.053, 0.170) | 734.9 | 897.9 |