Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Dermatology and Therapy
Published in: Dermatology and Therapy 1/2020

Open Access 01-02-2020 | Etanercept | Original Research

Rapid Response of Biologic Treatments of Moderate-to-Severe Plaque Psoriasis: A Comprehensive Investigation Using Bayesian and Frequentist Network Meta-analyses

Authors: Richard B. Warren, Kyoungah See, Russel Burge, Ying Zhang, Alan Brnabic, Gaia Gallo, Alyssa Garrelts, Alexander Egeberg

Published in: Dermatology and Therapy | Issue 1/2020

Login to get access

Abstract

Introduction

Rapid improvement of psoriasis is valued by patients and should be considered to be an important factor in treatment selection. We investigated Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) response rates within the first 12 weeks of treatment to compare the rapid response of 11 biologic therapies for moderate-to-severe psoriasis using Bayesian and Frequentist network meta-analyses (NMA).

Methods

A systematic literature review was conducted to identify phase 3, double-blind, randomized, controlled trials for adult patients with moderate-to-severe psoriasis treated with interleukin (IL)-17 (brodalumab, ixekizumab, secukinumab), IL-12/-23 (ustekinumab), IL-23 (guselkumab, risankizumab, tildrakizumab), or tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab). Outcome measures extracted from 32 publications were ≥ 75, ≥ 90, or 100% improvement in PASI score (PASI  75, PASI 90, or PASI 100, respectively) at weeks 2, 4, 8, and 12 and DLQI    (0,1), where score (0,1) indicates no effect on patient's life, at week 12. Bayesian NMA (BNMA) used fixed-treatment effect and random-baseline effect, normal independent models. Frequentist NMA (fNMA) was conducted as sensitivity analyses to test the robustness of the findings.

Results

Based on BNMA and fNMA, brodalumab and ixekizumab showed the most rapid treatment effects on PASI 75 at weeks 2, 4, and 8 and on PASI 90 and PASI 100 at weeks 2, 4, 8, and 12; ixekizumab overlapped with risankizumab on PASI 75 at week 12. Brodalumab, ixekizumab, and secukinumab yielded higher DLQI (0,1) gains at week 12 compared to all of the other biologics studied. Additional measures of quality of life were not assessed in this report.

Conclusions

Ixekizumab and brodalumab provide the most rapid response and earliest clinical benefit at week 2 among all of the biologics studied, including other biologic treatments such as secukinumab, ustekinumab, guselkumab, adalimumab, and etanercept. BNMA and fNMA results showed similar relative effect estimates and treatment rankings.

Funding

Eli Lilly and Company.
Appendix
Available only for authorised users
Literature
1.
Vanderpuye-Orgle J, Zhao Y, Lu J, et al. Evaluating the economic burden of psoriasis in the United States. J Am Acad Dermatol. 2015;72(961-7):e5.
2.
3.
Warren RB, Brnabic A, Saure D, et al. Matching-adjusted indirect comparison of efficacy in patients with moderate-to-severe plaque psoriasis treated with ixekizumab vs. secukinumab. Br J Dermatol. 2017;178:1064–71.CrossRef
4.
Papp KA, Lebwohl MG. Onset of action of biologics in patients with moderate-to-severe psoriasis. J Drugs Dermatol. 2017;17:247–50.
5.
Ogawa E, Sato Y, Minagawa A, Okuyama R. Pathogenesis of psoriasis and development of treatment. J Dermatol. 2018;45:264–72.PubMedCrossRef
6.
Liu L, Lu J, Allan BW, et al. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A. J Inflamm Res. 2016;9:39–50.PubMedPubMedCentralCrossRef
7.
Uhlenhake EE, Kurkowski D, Feldman SR. Conversations on psoriasis—what patients want and what physicians can provide: a qualitative look at patient and physician expectations. J Dermatolog Treat. 2010;21:6–12.PubMedCrossRef
8.
Blome C, Gosau R, Radtke MA, et al. Patient-relevant treatment goals in psoriasis. Arch Dermatol Res. 2016;308:69–78.PubMedCrossRef
9.
Korman NJ, Zhao Y, Lu J, Tran MH. Psoriasis disease severity affects patient satisfaction with treatment. Dermatol Online J. 2015;21(7).
10.
Seston EM, Ashcroft DM, Griffiths CE. Balancing the benefits and risks of drug treatment: a stated-preference, discrete choice experiment with patients with psoriasis. Arch Dermatol. 2007;143:1175–9.PubMedCrossRef
11.
Lebwohl M, Blauvelt A, Paul C, et al. Certolizumab pegol for the treatment of chronic plaque psoriasis: results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placebo-controlled study (CIMPACT). J Am Acad Dermatol. 2018;79(266–76):e5.
12.
Gottlieb AB, Blauvelt A, Thaҫi D, et al. Certolizumab pegol for the treatment of chronic plaque psoriasis: results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2). J Am Acad Dermatol. 2018;79(302–14):e6.
13.
Bagel J, Nia J, Hashim PW, et al. Secukinumab is superior to ustekinumab in clearing skin in patients with moderate to severe plaque psoriasis (16-week CLARITY results). Dermatol Ther (Heidelb). 2018;8:571–9.PubMedPubMedCentralCrossRef
14.
Thaҫi D, Blauvelt A, Reich K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol. 2015;73:400–9.CrossRef
15.
Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med. 2014;371:326–38.PubMedCrossRef
16.
Saurat JH, Stingl G, Dubertret L, et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol. 2008;158:558–66.PubMedCrossRef
17.
Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol. 2008;58:106–15.PubMedCrossRef
18.
Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76:405–17.PubMedCrossRef
19.
Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76:418–31.PubMedCrossRef
20.
Cai L, Gu J, Zheng J, et al. Efficacy and safety of adalimumab in Chinese patients with moderate-to-severe plaque psoriasis: results from a phase 3, randomized, placebo-controlled, double-blind study. J Eur Acad Dermatol Venereol. 2017;31:89–95.PubMedCrossRef
21.
Papp KA, Reich K, Paul C, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2016;175:273–86.PubMedCrossRef
22.
Lebwohl M, Strober B, Menter A, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373:1318–28.PubMedCrossRef
23.
Papp KA, Tyring S, Lahfa M, et al. A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol. 2005;152:1304–12.PubMedCrossRef
24.
Griffiths CE, Strober BE, van de Kerkhof P, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010;362:118–28.PubMedCrossRef
25.
Griffiths CE, Reich K, Lebwohl M, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386:541–51.PubMedCrossRef
26.
Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:345–56.PubMedCrossRef
27.
Reich K, Papp KA, Blauvelt A, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017;390:276–88.PubMedCrossRef
28.
29.
Reich K, Armstrong A, Blauvelt A, et al. Guselkumab demonstrates superior long-term responses compared with secukinumab in the treatment of moderate to severe plaque psoriasis: Results from the ECLIPSE trial. Poster presented at the 6th Congress of the Skin Inflammation & Psoriasis International Network, Paris, France, 25–27 April 2019.
30.
Langley R, Blauvelt A, Armstrong A, et al. Guselkumab demonstrates superior long-term responses to secukinumab at week 48 in the treatment of moderate to severe psoriasis: results from the ECLIPSE trial. Poster presented at the 3rd Inflammatory Skin Disease Summit, Vienna, Austria, 12–15 December 2019.
31.
Reich K, Nestle FO, Papp K, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet. 2005;366:1367–74.PubMedCrossRef
32.
Menter A, Feldman SR, Weinstein GD, et al. A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2007;56:31.e1–15.PubMedCrossRef
33.
Reich K, Pinter A, Lacour JP, et al. Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study. Br J Dermatol. 2017;177:1014–23.PubMedCrossRef
34.
Paul C, Griffiths CEM, van de Kerkhof PCM, et al. Ixekizumab provides superior efficacy compared with ustekinumab over 52 weeks of treatment: results from IXORA-S, a phase 3 study. J Am Acad Dermatol. 2019;80(70–9):e3.
35.
Langley RG, Papp K, Gooderham M, et al. Efficacy and safety of continuous every-2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase III trial (IXORA-P). Br J Dermatol. 2018;178:1315–23.PubMedCrossRef
36.
Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392:650–61.PubMedCrossRef
37.
Blauvelt A, Prinz JC, Gottlieb AB, et al. Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol. 2015;172:484–93.PubMedCrossRef
38.
Paul C, Lacour JP, Tedremets L, et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol. 2015;29:1082–90.PubMedCrossRef
39.
Tsai TF, Ho JC, Song M, et al. Efficacy and safety of ustekinumab for the treatment of moderate-to-severe psoriasis: a phase III, randomized, placebo-controlled trial in Taiwanese and Korean patients (PEARL). J Dermatol Sci. 2011;63:154–63.PubMedCrossRef
40.
Leonardi CL, Kimball AB, Papp KA, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008;371:1665–74.PubMedCrossRef
41.
Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371:1675–84.PubMedCrossRef
42.
Igarashi A, Kato T, Kato M, Song M, Nakagawa H. Efficacy and safety of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis: long-term results from a phase 2/3 clinical trial. J Dermatol. 2012;39:242–52.PubMedCrossRef
43.
44.
Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades AE. Evidence synthesis for decision making 4: inconsistency in networks of evidence based on randomized controlled trials. Med Decis Making. 2013;33:641–56.PubMedPubMedCentralCrossRef
45.
Dias S, Welton NJ, Sutton AJ, Ades AE. NICE DSU Technical Support Document 2: A generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. 2011, last updated 2016. http://​www.​nicedsu.​org.​uk. Accessed 8 Oct 2019.
46.
Brooks SP, Gelman A. General methods for monitoring convergence of iterative simulations. J Comput Graph Stat. 1998;7:434–55.MathSciNet
47.
Rücker G. Network meta-analysis, electrical networks and graph theory. Res Synth Methods. 2012;3:312–24.PubMedCrossRef
48.
Blauvelt A, Papp KA, Lebwohl MG, et al. Rapid onset of action in patients with moderate-to-severe psoriasis treated with brodalumab: a pooled analysis of data from two phase 3 randomized clinical trials (AMAGINE-2 and AMAGINE-3). J Am Acad Dermatol. 2017;77:372–4.PubMedCrossRef
49.
Leonardi C. Rapid onset of efficacy in patients with psoriasis treated with ixekizumab: A pooled analysis of data from two phase 3 randomized clinical trials (UNCOVER-2 and UNCOVER-3). J Am Acad Dermatol. 2016;74:AB70.CrossRef
50.
Pinter A, Amato D, Burge R, et al. Ixekizumab treatment results in more rapid clinical improvements in patients with moderate-to-severe psoriasis compared to ustekinumab: results from the IXORA-S trial. Poster presented at the American Academy of Dermatology Annual Meeting, Washington DC, 1–5 March 2019.
51.
Torbica A, Fattore G, Ayala F. Eliciting preferences to inform patient-centred policies: the case of psoriasis. Pharmacoeconomics. 2014;32:209–23.PubMedCrossRef
52.
Paul C, Guenther L, Torii H, et al. Impact of ixekizumab on facial psoriasis and related quality of life measures in moderate-to-severe psoriasis patients: 12-week results from two phase III trials. J Eur Acad Dermatol Venereol. 2018;32:68–72.PubMedCrossRef
53.
Kimball AB, Gieler U, Linder D, Sampogna F, Warren RB, Augustin M. Psoriasis: is the impairment to a patient’s life cumulative? J Eur Acad Dermatol Venereol. 2010;24:989–1004.PubMedCrossRef
54.
Yosipovitch G, Reich A, Steinhoff M, et al. Impact of ixekizumab treatment on itch and Psoriasis Area and Severity Index in patients with moderate-to-severe plaque psoriasis: an integrated analysis of two phase III randomized studies. Dermatol Ther (Heidelb). 2018;8:621–37.PubMedCrossRef
55.
Augustin M, Gooderham M, Amato D, et al. Rapid clinical response predicts consistent long-term response in patients with moderate-to-severe psoriasis: ixekizumab versus ustekinumab. Poster presented at the American Academy of Dermatology Annual Meeting, Washington DC, 1–5 March 2009.
56.
Strohal R, Prinz JC, Girolomoni G, Nast A. A patient-centred approach to biological treatment decision making for psoriasis: an expert consensus. J Eur Acad Dermatol Venereol. 2015;29:2390–8.PubMedPubMedCentralCrossRef
57.
Hoaglin DC, Hawkins N, Jansen JP, et al. Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2. Value Health. 2011;14:429–37.PubMedCrossRef
Metadata
Title
Rapid Response of Biologic Treatments of Moderate-to-Severe Plaque Psoriasis: A Comprehensive Investigation Using Bayesian and Frequentist Network Meta-analyses
Authors
Richard B. Warren
Kyoungah See
Russel Burge
Ying Zhang
Alan Brnabic
Gaia Gallo
Alyssa Garrelts
Alexander Egeberg
Publication date
01-02-2020
Publisher
Springer Healthcare
Published in
Dermatology and Therapy / Issue 1/2020
Print ISSN: 2193-8210
Electronic ISSN: 2190-9172
DOI
https://doi.org/10.1007/s13555-019-00337-y

Other articles of this Issue 1/2020

Dermatology and Therapy 1/2020 Go to the issue

Case Report

Incontinentia Pigmenti Associated with Aplasia Cutis Congenita in a Newborn Male with Klinefelter Syndrome: Is the Severity of Neurological Involvement Linked to Skin Manifestations?

Original Research

Prospective Evaluation of the Efficacy of a Food Supplement in Increasing Photoprotection and Improving Selective Markers Related to Skin Photo-Ageing

Correction

Correction to: Pathogenesis, Clinical Signs and Treatment Recommendations in Brittle Nails: A Review

Original Research

A Comparison of Azathioprine and Mycophenolate Mofetil as Adjuvant Drugs in Patients with Pemphigus: A Retrospective Cohort Study

Original Research

Safety of Ixekizumab Treatment for up to 5 Years in Adult Patients with Moderate-to-Severe Psoriasis: Results from Greater Than 17,000 Patient-Years of Exposure

Original Research

Exploring Anti-Fungal, Anti-Microbial and Anti-Inflammatory Properties of a Topical Non-Steroidal Barrier Cream in Face and Chest Seborrheic Dermatitis
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits