Journal of Dermatological Treatment

peerreview_statement

aims_and_scope_url

publication_history

received

accepted

published

Guangdong Basic and Applied Basic Research Foundation Committee

The Sanming Project of Medicine in Shenzhen

The High Level-Hospital Program, Health Commission of Guangdong Province, China

Chinese Guidelines for the Diagnosis and Treatment of Psoriasis (2018 Complete Edition)

Chin J Dermatol

This study aims to evaluate the clinical efficacy, recurrence rate, and drug retention rate of plaque psoriasis with different severity levels treated with Ixekizumab.
A retrospective, multicenter, real-world study was conducted using the China Cathay database to analyze 354 Chinese patients with mild-to-moderate and severe psoriasis who received ixekizumab therapy. Psoriasis Area and Severity Index (PASI) 75/90/100 response rates, absolute PASI values, 3-year drug retention, and recurrence rates were assessed at 2, 4, 12, 24, and 52 weeks.
The baseline PASI scores for the mild-to-moderate group (PASI <10) and severe group (PASI ≥ 10) were 5.6± 2.6 and 20 ± 11, respectively. Except for a difference in the proportion of male patients, there were no differences between the two groups in terms of age,duration of illness, hypertension, hyperlipidemia, cardiovascular diseases, gout and arthropathy. The mild-moderate group showed superior PASI75/90 responses at most timepoints and consistently higher PASI100 rates (all 
Ixekizumab demonstrates superior efficacy in mild-moderate versus severe psoriasis, suggesting greater benefit with early biologic intervention.

Clinical efficacy, drug retention and recurrence of ixekizumab across psoriasis severities: a multicenter retrospective analysis of 354 patients.

Clinical efficacy, drug retention and recurrence of ixekizumab across psoriasis severities: a multicenter retrospective analysis of 354 patients

JAMA Dermatology

<jats:sec id="ab-doi250038-4"><jats:title>Importance</jats:title><jats:p>Patients with psoriasis may require a switch to another therapy due to high treatment costs, primary effectiveness failure, biologic fatigue, or adverse effects associated with the initial biologic treatment; however, the availability of evidence for the effectiveness and safety of interclass biologic switching for the treatment of psoriasis is unknown.</jats:p></jats:sec><jats:sec id="ab-doi250038-5"><jats:title>Objective</jats:title><jats:p>To investigate the effectiveness and safety of psoriasis treatment after the failure of initial biologic therapy, particularly when patients switch to a second biologic.</jats:p></jats:sec><jats:sec id="ab-doi250038-6"><jats:title>Data Sources</jats:title><jats:p>PubMed, Embase, and the Cochrane Library were searched from inception through January 25, 2025.</jats:p></jats:sec><jats:sec id="ab-doi250038-7"><jats:title>Study Selection</jats:title><jats:p>The study included randomized clinical trials (RCTs) of patients with plaque psoriasis aged 18 years or older involving crossover or switching from 1 biologic agent to another initial biologic within the same or different drug class.</jats:p></jats:sec><jats:sec id="ab-doi250038-8"><jats:title>Data Extraction and Synthesis</jats:title><jats:p>Two researchers independently screened the records and abstracted data using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Data were pooled using random-effects models.</jats:p></jats:sec><jats:sec id="ab-doi250038-9"><jats:title>Main Outcomes and Measures</jats:title><jats:p>The prespecified primary end point was psoriasis area and severity index (PASI) 90. Secondary end points included clinician- and patient-reported outcomes (PROMs) and safety. Clinical effectiveness was evaluated based on the PASI responses (PASI 75, 90, and 100) and the Investigator’s and Physician’s Global Assessments scores of 0 or 1 and body surface area of 1% or less. PROMs included the dermatology life quality index and psoriasis symptoms and signs diary. Safety concerns included adverse events (AEs), serious AEs, severe AEs, treatment-related AEs, and specific AEs.</jats:p></jats:sec><jats:sec id="ab-doi250038-10"><jats:title>Results</jats:title><jats:p>Twenty-four RCTs involving 12 661 patients with psoriasis and 8 switching categories were analyzed. Significant differences observed in PASI 90 between week 4 and week 0 (odds ratio [OR], 6.53; 95% CI, 2.58-16.51). Substantial disparities were noted across various PASI response metrics, specifically PASI 90 (OR, 28.61; 95% CI, 12.89-63.47), PASI 75 (OR, 11.11; 95% CI, 5.95-20.75), and PASI 100 (OR, 18.76; 95% CI, 8.37-42.01). No difference exists in safety outcomes between the end point and week 0, including in serious AEs (OR, 1.63; 95% CI, 0.72-3.69), severe AEs (OR, 1.40; 95% CI, 0.61-3.26), and treatment-related AEs (OR, 1.79; 95% CI, 0.41-7.88). The highest risk of infection was associated with switching from anti−TNF-α agents to anti−interleukin (IL)-23p19, anti−IL-17A, or anti−IL-12/23p40 agents, with infection rates of 0.62%, 0.54% and 0.39%, respectively.</jats:p></jats:sec><jats:sec id="ab-doi250038-11"><jats:title>Conclusions and Relevance</jats:title><jats:p>This systematic review and meta-analysis found that interclass biologic switching was effective in a significant number of patients. With the introduction of biologics with diverse mechanisms of action, these options may become viable and potentially superior. However, further confirmatory data from larger patient cohorts and longer follow-up periods are required to obtain more conclusive results. Our results highlight the importance of vigilance for infections when switching biologics.</jats:p></jats:sec>

Psoriasis: emerging therapeutic strategies.

Nat Rev Drug Discov

Switching biologics in psoriasis - practical guidance and evidence to support.

Expert Rev Clin Pharmacol

Biologic fatigue in psoriasis.

J Dermatolog Treat

Therapeutic strategies: rotational therapy and combinations.

Clin Exp Dermatol

Formation and clinical effects of anti-drug antibodies against biologics in psoriasis treatment: an analysis of current evidence.

Autoimmun Rev

Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.

J Am Acad Dermatol

Impact of switching between reference biologics and biosimilars of tumour necrosis factor inhibitors for rheumatoid arthritis: a systematic review and network meta-analysis.

Sci Rep

Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases.

Ann Rheum Dis

Systematic review of efficacy of anti-tumor necrosis factor (TNF) therapy in patients with psoriasis previously treated with a different anti-TNF agent.

Long-term efficacy and safety of ixekizumab: a 5-year analysis of the UNCOVER-3 randomized controlled trial.

Dermatology Life Quality Index (DLQI)–a simple practical measure for routine clinical use.

Measurement properties of a patient-reported outcome measure assessing psoriasis severity: The psoriasis symptoms and signs diary.

Safety and efficacy of bimekizumab through 2 years in patients with moderate-to-severe plaque psoriasis: longer-term results from the BE SURE randomized controlled trial and the open-label extension from the BE BRIGHT trial.

Br J Dermatol

Bimekizumab versus adalimumab in plaque psoriasis.

N Engl J Med

Bimekizumab efficacy and safety in patients with moderate to severe plaque psoriasis: two-year interim results from the open-label extension of the randomized BE RADIANT phase 3b trial.

Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial.

Bimekizumab efficacy and safety in patients with moderate-to-severe plaque psoriasis who switched from adalimumab, ustekinumab or secukinumab: results from phase III/IIIb trials.

Safety of guselkumab in patients with moderate-to-severe psoriasis treated through 100 weeks: a pooled analysis from the randomized VOYAGE 1 and VOYAGE 2 studies.

Consistent safety profile with up to 5 years of continuous treatment with guselkumab: Pooled analyses from the phase 3 VOYAGE 1 and VOYAGE 2 trials of patients with moderate-to-severe psoriasis.

Maintenance of skin clearance with ixekizumab treatment of psoriasis: three-year results from the UNCOVER-3 study.

Ixekizumab sustains high level of efficacy and favourable safety profile over 4 years in patients with moderate psoriasis: results from UNCOVER-3 study.

J Eur Acad Dermatol Venereol

Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial.

Lancet

Five-year efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis who respond at week 28: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2).

Diagnosis and management of common tinea infections.

Am Fam Physician

Management of acute upper respiratory tract infection: the role of early intervention.

Expert Rev Respir Med

Latent tuberculosis: two centuries of confusion.

Am J Respir Crit Care Med

The epidemiology of urinary tract infection.

Nat Rev Urol

The complexity of adverse side-effects to biological agents.

J Crohns Colitis

Efficacy and safety of brodalumab in patients with psoriasis who had inadequate responses to ustekinumab: subgroup analysis of two randomized phase III trials.

Long-term efficacy of guselkumab for the treatment of moderate-to-severe psoriasis: results from the phase 3 VOYAGE 1 trial through two years.

J Drugs Dermatol

Efficacy and safety of switching to ixekizumab in etanercept non-responders: a subanalysis from two phase III randomized clinical trials in moderate-to-severe plaque psoriasis (UNCOVER-2 and -3).

Am J Clin Dermatol

Efficacy and safety of tildrakizumab for plaque psoriasis with continuous dosing, treatment interruption, dose adjustments and switching from etanercept: results from phase III studies.

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis: Subgroup analysis of Latin American patients in the phase 3 randomized UNCOVER-3 study.

Actas Dermosifiliogr

Efficacy and safety of ixekizumab for the treatment of moderate-to-severe plaque psoriasis: Results through 108 weeks of a randomized, controlled phase 3 clinical trial (UNCOVER-3).

Continuous treatment with guselkumab maintains clinical responses through 4 years in patients with moderate-to-severe psoriasis: results from VOYAGE 1.

Efficacy of switching to risankizumab compared with continued adalimumab treatment in patients with moderate-to-severe plaque psoriasis.

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.

Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis.

Maintenance of response through up to 4 years of continuous guselkumab treatment of psoriasis in the VOYAGE 2 phase 3 study.

Five-year maintenance of clinical response and health-related quality of life improvements in patients with moderate-to-severe psoriasis treated with guselkumab: results from VOYAGE 1 and VOYAGE 2.

Patients with persistent mild psoriasis after treatment with ustekinumab achieved greater improvements in skin clearance and patient-reported outcomes after switching to guselkumab in the phase 3 NAVIGATE Trial.

Acta Derm Venereol

Risk of Candida infection and serious infections in patients with moderate-to-severe psoriasis receiving biologics: a systematic review and meta-analysis of randomized controlled trials.

Int J Clin Pract

Th17 cells in immunity to Candida albicans.

Cell Host Microbe

Psoriasis and treatment: past, present and future aspects.

Does the treatment ladder for systemic therapy in moderate to severe psoriasis only go up? The percentage of patients with severe psoriasis on biologics increases over time.

Biosimilars for the treatment of psoriasis: a systematic review of clinical trials and observational studies.

JAMA Dermatol

A review of switching biologic agents in the treatment of moderate-to-severe plaque psoriasis.

Clin Drug Investig

Differential regulation of IL-17A and IL-17F via STAT5 contributes to psoriatic disease.

J Allergy Clin Immunol

The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

Front Immunol

Patients with psoriasis may require a switch to another therapy due to high treatment costs, primary effectiveness failure, biologic fatigue, or adverse effects associated with the initial biologic treatment; however, the availability of evidence for the effectiveness and safety of interclass biologic switching for the treatment of psoriasis is unknown.
To investigate the effectiveness and safety of psoriasis treatment after the failure of initial biologic therapy, particularly when patients switch to a second biologic.
PubMed, Embase, and the Cochrane Library were searched from inception through January 25, 2025.
The study included randomized clinical trials (RCTs) of patients with plaque psoriasis aged 18 years or older involving crossover or switching from 1 biologic agent to another initial biologic within the same or different drug class.
Two researchers independently screened the records and abstracted data using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Data were pooled using random-effects models.
The prespecified primary end point was psoriasis area and severity index (PASI) 90. Secondary end points included clinician- and patient-reported outcomes (PROMs) and safety. Clinical effectiveness was evaluated based on the PASI responses (PASI 75, 90, and 100) and the Investigator's and Physician's Global Assessments scores of 0 or 1 and body surface area of 1% or less. PROMs included the dermatology life quality index and psoriasis symptoms and signs diary. Safety concerns included adverse events (AEs), serious AEs, severe AEs, treatment-related AEs, and specific AEs.
Twenty-four RCTs involving 12 661 patients with psoriasis and 8 switching categories were analyzed. Significant differences observed in PASI 90 between week 4 and week 0 (odds ratio [OR], 6.53; 95% CI, 2.58-16.51). Substantial disparities were noted across various PASI response metrics, specifically PASI 90 (OR, 28.61; 95% CI, 12.89-63.47), PASI 75 (OR, 11.11; 95% CI, 5.95-20.75), and PASI 100 (OR, 18.76; 95% CI, 8.37-42.01). No difference exists in safety outcomes between the end point and week 0, including in serious AEs (OR, 1.63; 95% CI, 0.72-3.69), severe AEs (OR, 1.40; 95% CI, 0.61-3.26), and treatment-related AEs (OR, 1.79; 95% CI, 0.41-7.88). The highest risk of infection was associated with switching from anti-TNF-α agents to anti-interleukin (IL)-23p19, anti-IL-17A, or anti-IL-12/23p40 agents, with infection rates of 0.62%, 0.54% and 0.39%, respectively.
This systematic review and meta-analysis found that interclass biologic switching was effective in a significant number of patients. With the introduction of biologics with diverse mechanisms of action, these options may become viable and potentially superior. However, further confirmatory data from larger patient cohorts and longer follow-up periods are required to obtain more conclusive results. Our results highlight the importance of vigilance for infections when switching biologics.

Biopharmaceutical Switching in Psoriasis Treatment: A Systematic Review and Meta-Analysis.

Biopharmaceutical Switching in Psoriasis Treatment

<jats:sec><jats:title>Importance</jats:title><jats:p>New, effective, and well-tolerated oral therapies are needed for treating psoriasis. Zasocitinib, a highly selective allosteric tyrosine kinase 2 (TYK2) inhibitor, is a potential new oral treatment for this disease.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To assess the efficacy, safety, and tolerability of zasocitinib in patients with moderate to severe plaque psoriasis.</jats:p></jats:sec><jats:sec><jats:title>Design, Setting, and Participants</jats:title><jats:p>This phase 2b, randomized, double-blind, placebo-controlled, multiple-dose randomized clinical trial was conducted from August 11, 2021, to September 12, 2022, at 47 centers in the US and 8 in Canada. The study included a 12-week treatment period and a 4-week follow-up period. Key eligibility criteria for participants included age 18 to 70 years; a Psoriasis Area and Severity Index (PASI) score of 12 or greater; a Physician’s Global Assessment score of 3 or greater; and a body surface area covered by plaque psoriasis of 10% or greater. Of 287 patients randomized, 259 (90.2%) received at least 1 dose of study treatment.</jats:p></jats:sec><jats:sec><jats:title>Intervention</jats:title><jats:p>Patients were randomly assigned (1:1:1:1:1) to receive zasocitinib at 2, 5, 15, or 30 mg or placebo orally, once daily, for 12 weeks.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes and Measures</jats:title><jats:p>The primary efficacy end point was the proportion of patients achieving 75% or greater improvement in PASI score (PASI 75) at week 12. Secondary efficacy end points included PASI 90 and 100 responses. Safety was also assessed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In total, 259 patients were randomized and received treatment (mean [SD] age, 47 [13] years; 82 women [32%]). At week 12, PASI 75 was achieved for 9 (18%), 23 (44%), 36 (68%), and 35 (67%) patients receiving zasocitinib at 2, 5, 15, and 30 mg, respectively, and 3 patients (6%) receiving placebo. PASI 90 responses were consistent with PASI 75. PASI 100 demonstrated a dose response at all doses, with 17 patients (33%) achieving PASI 100 with zasocitinib, 30 mg. Treatment-emergent adverse events occurred for 23 patients (44%) receiving placebo and 28 (53%) to 31 (62%) patients receiving the 4 different doses of zasocitinib, with no dose dependency and no clinically meaningful longitudinal differences in laboratory parameters.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>This randomized clinical trial found that potent and selective inhibition of TYK2 with zasocitinib at oral doses of 5 mg or more once daily resulted in greater skin clearance than placebo over 12 weeks.</jats:p></jats:sec><jats:sec><jats:title>Trial Registration</jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/study/NCT04999839?locStr=United%20States&amp;amp;amp;country=United%20States&amp;amp;amp;cond=Plaque%20Psoriasis&amp;amp;amp;intr=placebo&amp;amp;amp;term=NCT04999839&amp;amp;amp;rank=1">NCT04999839</jats:ext-link></jats:p></jats:sec>

Impact of psoriatic disease on quality of life: interim results of a global survey.

Dermatol Ther (Heidelb)

Quality of life and work productivity impairment among psoriasis patients: findings from the National Psoriasis Foundation survey data 2003-2011.

PLoS One

Psoriasis prevalence and severity by expert elicitation.

Psoriasis pathogenesis and the development of novel targeted immune therapies.

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

Cochrane Database Syst Rev

Janus kinases in immune cell signaling.

Immunol Rev

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity.

Sci Transl Med

The psoriasis-protective TYK2 I684S variant impairs IL-12 stimulated pSTAT4 response in skin-homing CD4+ and CD8+ memory T-cells.

Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity.

Nat Genet

TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits.

Association of TYK2 rs34536443 polymorphism with susceptibility to systemic lupus erythematous in the Iranian population.

Rheumatology Research

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.

Nature

Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials.

Oral Janus kinase inhibitors in the treatment of atopic dermatitis: a systematic review and meta-analysis.

Skin Health Dis

Janus kinase inhibitors for alopecia areata: a systematic review and meta-analysis.

JAMA Netw Open

Janus kinase inhibitors in the treatment of vitiligo: a review.

The safety of JAK-1 inhibitors.

Rheumatology (Oxford)

Managing cardiovascular and cancer risk associated with JAK inhibitors.

Drug Saf

Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis.

Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial.

Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 program for evaluation of TYK2 inhibitor psoriasis second trial.

Discovery of a potent and selective tyrosine kinase 2 inhibitor: TAK-279.

J Med Chem

33226 Analysis of histologic and molecular improvement in moderate-to-severe psoriasis: results from a phase 1b trial of the novel allosteric TYK2 inhibitor NTX-973.

CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials.

Severe psoriasis—oral therapy with a new retinoid.

Dermatologica

Dermatology Life Quality Index (DLQI)—a simple practical measure for routine clinical use.

Relationship between clinical response to therapy and health-related quality of life outcomes in patients with moderate to severe plaque psoriasis.

Dermatology

Total skin clearance results in improvements in health-related quality of life and reduced symptom severity among patients with moderate to severe psoriasis.

Clinical meaningfulness of complete skin clearance in psoriasis.

Association between patient- and physician-reported outcomes in patients with moderate-to-severe plaque psoriasis treated with biologics in real life (PSO-BIO-REAL).

Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial.

Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase II regimen-finding study.

317 Characterization of pharmacokinetics, pharmacodynamics, tolerability and clinical activity in phase I studies of the novel allosteric tyrosine kinase 2 (TYK2) inhibitor NDI-034858.

J Invest Dermatol

New, effective, and well-tolerated oral therapies are needed for treating psoriasis. Zasocitinib, a highly selective allosteric tyrosine kinase 2 (TYK2) inhibitor, is a potential new oral treatment for this disease.
To assess the efficacy, safety, and tolerability of zasocitinib in patients with moderate to severe plaque psoriasis.
This phase 2b, randomized, double-blind, placebo-controlled, multiple-dose randomized clinical trial was conducted from August 11, 2021, to September 12, 2022, at 47 centers in the US and 8 in Canada. The study included a 12-week treatment period and a 4-week follow-up period. Key eligibility criteria for participants included age 18 to 70 years; a Psoriasis Area and Severity Index (PASI) score of 12 or greater; a Physician's Global Assessment score of 3 or greater; and a body surface area covered by plaque psoriasis of 10% or greater. Of 287 patients randomized, 259 (90.2%) received at least 1 dose of study treatment.
Patients were randomly assigned (1:1:1:1:1) to receive zasocitinib at 2, 5, 15, or 30 mg or placebo orally, once daily, for 12 weeks.
The primary efficacy end point was the proportion of patients achieving 75% or greater improvement in PASI score (PASI 75) at week 12. Secondary efficacy end points included PASI 90 and 100 responses. Safety was also assessed.
In total, 259 patients were randomized and received treatment (mean [SD] age, 47 [13] years; 82 women [32%]). At week 12, PASI 75 was achieved for 9 (18%), 23 (44%), 36 (68%), and 35 (67%) patients receiving zasocitinib at 2, 5, 15, and 30 mg, respectively, and 3 patients (6%) receiving placebo. PASI 90 responses were consistent with PASI 75. PASI 100 demonstrated a dose response at all doses, with 17 patients (33%) achieving PASI 100 with zasocitinib, 30 mg. Treatment-emergent adverse events occurred for 23 patients (44%) receiving placebo and 28 (53%) to 31 (62%) patients receiving the 4 different doses of zasocitinib, with no dose dependency and no clinically meaningful longitudinal differences in laboratory parameters.
This randomized clinical trial found that potent and selective inhibition of TYK2 with zasocitinib at oral doses of 5 mg or more once daily resulted in greater skin clearance than placebo over 12 weeks.
ClinicalTrials.gov Identifier: NCT04999839.

Tyrosine Kinase 2 Inhibition With Zasocitinib (TAK-279) in Psoriasis: A Randomized Clinical Trial.

Tyrosine Kinase 2 Inhibition With Zasocitinib (TAK-279) in Psoriasis

<jats:sec><jats:title>Importance</jats:title><jats:p>Psoriasis is a chronic inflammatory skin disease with unmet needs for tailored treatment and therapy de-escalation strategies.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To evaluate early intervention with and prolonging the dosing interval for guselkumab, a p19 subunit-targeted interleukin (IL)-23 inhibitor, in patients with moderate to severe psoriasis.</jats:p></jats:sec><jats:sec><jats:title>Design, Setting, and Participants</jats:title><jats:p>The GUIDE clinical trial is an ongoing phase 3b, randomized, double-blinded trial conducted across 80 centers in Germany and France comprising 3 parts evaluating the impact of early disease intervention, prolonged dosing interval, and maintenance of response following treatment withdrawal among adults with moderate to severe plaque psoriasis. In study part 2, reported herein, first and last patient visits were September 2019 and March 2022, respectively.</jats:p></jats:sec><jats:sec><jats:title>Interventions</jats:title><jats:p>In GUIDE part 1 (week [W]0-W28), patients received guselkumab, 100 mg, at W0, W4, W12, and W20. Those achieving a Psoriasis Area and Severity Index (PASI) of 0 at both W20 and W28 were termed <jats:italic>super responders</jats:italic> (SRes). In part 2 (W28-W68), SRes were randomized to guselkumab, 100 mg, every 8 weeks or every 16 weeks; non-SRes continued open-label guselkumab every 8 weeks.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes and Measures</jats:title><jats:p>Primary objective was to demonstrate noninferiority (with a 10% margin) of guselkumab every 16 weeks vs every 8 weeks dosing among SRes for maintenance of disease control (PASI &amp;amp;lt;3 at W68). Biomarker substudies assessed immunologic effects in skin and blood.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Overall, 822 patients received guselkumab in part 2 (297 [36.1%] SRes [every 8 weeks/every 16 weeks; n = 148/n = 149] and 525 [63.9%] non-SRes). Among SRes, mean (SD) age was 39.4 (14.1) years, 95 (32.0%) were female, and 202 (68.0%) were male. The primary end point of noninferiority for guselkumab every 16 weeks vs every 8 weeks in SRes was met (<jats:italic>P</jats:italic> = .001), with 91.9% (137/149; 90% CI, 87.3%-95.3%) of SRes receiving every 16 weeks and 92.6% (137/148; 90% CI, 88.0%-95.8%) of SRes receiving dosing every 8 weeks having PASI lower than 3 at W68. Clinical effects corresponded with immunologic changes; skin CD8-positive tissue-resident memory T (TRM)–cell count decreased quickly from baseline, remaining low in both dosing groups. Similarly, serum IL-17A, IL-17F, IL-22, and β defensin (BD)–2 levels decreased significantly from baseline, remaining low in both dosing groups to W68. Guselkumab was well-tolerated; no new safety signals were identified.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>Psoriasis treatment guidelines lack or provide inconsistent advice on patient stratification and treatment de-escalation. We present the first randomized trial providing evidence that, in patients with early complete skin clearance at 2 consecutive visits (W20 and W28), extending the guselkumab dosing interval may control disease activity.</jats:p></jats:sec><jats:sec><jats:title>Trial Registration</jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://classic.clinicaltrials.gov/ct2/show/NCT03818035">NCT03818035</jats:ext-link></jats:p></jats:sec>

Psoriasis.

Nat Rev Dis Primers

Resident memory T cells in psoriasis: key to a cure?

J Psoriasis Psoriatic Arthritis

IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE).

BMJ Open

National consensus on biologic dose reduction in psoriasis: a modified eDelphi procedure.

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.

Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial.

Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance (‘clinical super response’): week 28 results from the ongoing phase IIIb randomized, double-blind, parallel-group, GUIDE study.

Differential changes in inflammatory mononuclear phagocyte and T-cell profiles within psoriatic skin during treatment with guselkumab vs. secukinumab.

Guselkumab efficacy after withdrawal is associated with suppression of serum IL-23-regulated IL-17 and IL-22 in psoriasis: VOYAGE 2 study.

Foxp3+ regulatory T cells of psoriasis patients easily differentiate into IL-17A-producing cells and are found in lesional skin.

Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - part 1: treatment goals and treatment recommendations.

J Dtsch Dermatol Ges

Psoriasis treat to target: defining outcomes in psoriasis using data from a real-world, population-based cohort study (the British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR).

ß-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis.

Population pharmacokinetic modeling of guselkumab, a human IgG1? monoclonal antibody targeting IL-23, in patients with moderate to severe plaque psoriasis.

J Clin Pharmacol

An international Delphi consensus to define a clinically appropriate definition of disease modification for plaque psoriasis.

Secukinumab dosing optimization in patients with moderate-to-severe plaque psoriasis: results from the randomized, open-label OPTIMISE study.

Dose tapering of biologics in patients with psoriasis: a scoping review.

Drugs

Extension of ustekinumab maintenance dosing interval in moderate-to-severe psoriasis: results of a phase IIIb, randomized, double-blinded, active-controlled, multicentre study (PSTELLAR).

Real-world performance of a new strategy for off-label use of guselkumab in moderate to severe psoriasis: super-responder patients as the epitome of efficacy and optimisation.

Significance of IL-17A-producing CD8+CD103+ skin resident memory T cells in psoriasis lesion and their possible relationship to clinical course.

J Dermatol Sci

CD8 resident memory T cells with interleukin 17A-producing potential are accumulated in disease-naïve nonlesional sites of psoriasis possibly in correlation with disease duration.

Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis.

Super-response to guselkumab treatment in patients with moderate-to-severe psoriasis: age, body weight, baseline Psoriasis Area and Severity Index, and baseline Investigator’s Global Assessment scores predict complete skin clearance.

Psoriasis is a chronic inflammatory skin disease with unmet needs for tailored treatment and therapy de-escalation strategies.
To evaluate early intervention with and prolonging the dosing interval for guselkumab, a p19 subunit-targeted interleukin (IL)-23 inhibitor, in patients with moderate to severe psoriasis.
The GUIDE clinical trial is an ongoing phase 3b, randomized, double-blinded trial conducted across 80 centers in Germany and France comprising 3 parts evaluating the impact of early disease intervention, prolonged dosing interval, and maintenance of response following treatment withdrawal among adults with moderate to severe plaque psoriasis. In study part 2, reported herein, first and last patient visits were September 2019 and March 2022, respectively.
In GUIDE part 1 (week [W]0-W28), patients received guselkumab, 100 mg, at W0, W4, W12, and W20. Those achieving a Psoriasis Area and Severity Index (PASI) of 0 at both W20 and W28 were termed super responders (SRes). In part 2 (W28-W68), SRes were randomized to guselkumab, 100 mg, every 8 weeks or every 16 weeks; non-SRes continued open-label guselkumab every 8 weeks.
Primary objective was to demonstrate noninferiority (with a 10% margin) of guselkumab every 16 weeks vs every 8 weeks dosing among SRes for maintenance of disease control (PASI <3 at W68). Biomarker substudies assessed immunologic effects in skin and blood.
Overall, 822 patients received guselkumab in part 2 (297 [36.1%] SRes [every 8 weeks/every 16 weeks; n = 148/n = 149] and 525 [63.9%] non-SRes). Among SRes, mean (SD) age was 39.4 (14.1) years, 95 (32.0%) were female, and 202 (68.0%) were male. The primary end point of noninferiority for guselkumab every 16 weeks vs every 8 weeks in SRes was met (P = .001), with 91.9% (137/149; 90% CI, 87.3%-95.3%) of SRes receiving every 16 weeks and 92.6% (137/148; 90% CI, 88.0%-95.8%) of SRes receiving dosing every 8 weeks having PASI lower than 3 at W68. Clinical effects corresponded with immunologic changes; skin CD8-positive tissue-resident memory T (TRM)-cell count decreased quickly from baseline, remaining low in both dosing groups. Similarly, serum IL-17A, IL-17F, IL-22, and β defensin (BD)-2 levels decreased significantly from baseline, remaining low in both dosing groups to W68. Guselkumab was well-tolerated; no new safety signals were identified.
Psoriasis treatment guidelines lack or provide inconsistent advice on patient stratification and treatment de-escalation. We present the first randomized trial providing evidence that, in patients with early complete skin clearance at 2 consecutive visits (W20 and W28), extending the guselkumab dosing interval may control disease activity.
ClinicalTrials.gov Identifier: NCT03818035.

Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis: The GUIDE Randomized Clinical Trial.

Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis

<jats:sec><jats:title>Importance</jats:title><jats:p>Atopic dermatitis (AD) and plaque psoriasis are inflammatory skin diseases with unmet need for effective topical treatments with few application site reactions.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To assess the efficacy and safety of the topical phosphodiesterase 4 inhibitor PF-07038124 in patients with AD and plaque psoriasis.</jats:p></jats:sec><jats:sec><jats:title>Design, Setting, and Participants</jats:title><jats:p>This phase 2a, randomized, double-blind clinical trial was conducted from December 21, 2020, to August 18, 2021, at 34 sites across 4 countries. Eligible patients (aged 18-70 years) had mild to moderate AD (covering 5%-20% body surface area) or plaque psoriasis (covering 5%-15% body surface area). Data were analyzed until December 15, 2021.</jats:p></jats:sec><jats:sec><jats:title>Interventions</jats:title><jats:p>Patients were randomized (1:1) to PF-07038124, 0.01%, topical ointment or vehicle once daily for 6 weeks.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes and Measures</jats:title><jats:p>The primary end point was the percent change from baseline (CFB) in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures included treatment-emergent adverse events, including application site reactions.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Overall, 104 patients were randomized (mean [SD] age, 43.0 [15.4] years; 55 [52.9%] women; 4 [3.8%] Asian, 13 [12.5%] Black, and 87 [83.7%] White), including 70 with AD (41 women [58.6%]; mean [SD] ages, 41.4 [16.6] years in the PF-07038124 group and 36.1 [13.9] years in the vehicle group) and 34 with plaque psoriasis (20 men [58.8%]; mean [SD] ages, 51.8 [12.3] years in the PF-07038124 group and 51.2 [10.8] years in the vehicle group). Baseline characteristics were generally balanced. At week 6, the PF-07038124 groups showed significantly greater improvements compared with vehicle groups in EASI (least-squares mean CFB,  −74.9% vs −35.5%; difference, −39.4% [90% CI, −58.8% to −20.1%]; <jats:italic>P</jats:italic> &amp;amp;lt; .001) and PASI scores (CFB, −4.8 vs 0.1; difference, −4.9 [90% CI, −7.0 to −2.8]; <jats:italic>P</jats:italic> &amp;amp;lt; .001). The number of patients with treatment-emergent adverse events was comparable between treatment groups in patients with AD (PF-07038124, 9 [25.0%]; vehicle, 9 [26.5%]) and plaque psoriasis (PF-07038124, 3 [17.6%]; vehicle, 6 [35.3%]). There were no application site reactions with PF-07038124 treatment.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>Topical PF-07038124 was well tolerated and demonstrated superior efficacy compared with vehicle in patients with mild to moderate AD and plaque psoriasis.</jats:p></jats:sec><jats:sec><jats:title>Trial Registration</jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/study/NCT04664153">NCT04664153</jats:ext-link></jats:p></jats:sec>

National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study.

Atopic dermatitis epidemiology and unmet need in the United Kingdom.

Tolerability of topical treatments for atopic dermatitis.

Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures.

Guidelines of care for the management of atopic dermatitis: section 2: management and treatment of atopic dermatitis with topical therapies.

Comparison of moisturizing creams for the prevention of atopic dermatitis relapse: a randomized double-blind controlled multicentre clinical trial.

The pathology of type 2 inflammation–associated itch in atopic dermatitis.

Diagnostics (Basel)

The cytokine mediated molecular pathophysiology of psoriasis and its clinical implications.

Int J Mol Sci

Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases.

Front Pharmacol

Effect of roflumilast cream vs vehicle cream on chronic plaque psoriasis: the DERMIS-1 and DERMIS-2 randomized clinical trials.

JAMA

Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1).

Atopic dermatitis: an expanding therapeutic pipeline for a complex disease.

Efficacy and Safety of PF-07038124 in Patients With Atopic Dermatitis and Plaque Psoriasis

Plaque Psoriasis in Dermatology Research

Clinical efficacy, drug retention and recurrence of ixekizumab across psoriasis severities: a multicenter retrospective analysis of 354 patients

Biopharmaceutical Switching in Psoriasis Treatment

Tyrosine Kinase 2 Inhibition With Zasocitinib (TAK-279) in Psoriasis

Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis

Efficacy and Safety of PF-07038124 in Patients With Atopic Dermatitis and Plaque Psoriasis

Oral orismilast: Efficacy and safety in moderate‐to‐severe psoriasis and development of modified release tablets

Papers