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>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.

J Invest Dermatol

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 id="ab-dbr230025-4"><jats:title>Importance</jats:title><jats:p>Laboratory testing for the presence of tuberculosis, hepatitis, and other conditions before starting most systemic immunomodulatory agents is recommended in patients with chronic inflammatory skin diseases (CISD) but current testing patterns in the US are unclear.</jats:p></jats:sec><jats:sec id="ab-dbr230025-5"><jats:title>Objective</jats:title><jats:p>To determine the prevalence of pretreatment testing that is recommended for patients with CISD (psoriasis, hidradenitis suppurativa, or atopic dermatitis).</jats:p></jats:sec><jats:sec id="ab-dbr230025-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This descriptive analysis of US commercial insurance claims databases from December 31, 2002, to December 31, 2020, included adult patients with CISD (psoriasis, hidradenitis suppurativa, or atopic dermatitis) who started an immunomodulatory agent, including methotrexate, tumor necrosis factor α inhibitors, interleukin (IL)–17Ai, ustekinumab, IL-23i, dupilumab, or apremilast.</jats:p></jats:sec><jats:sec id="ab-dbr230025-7"><jats:title>Main Outcomes and Measures</jats:title><jats:p>The proportion of patients who underwent the screening tests as suggested by professional societies—including for tuberculosis, hepatitis, and liver function; complete blood cell counts; and lipid panels—were determined within 6 months before and during 2 years after treatment start.</jats:p></jats:sec><jats:sec id="ab-dbr230025-8"><jats:title>Results</jats:title><jats:p>A total of 122 308 patients with CISDs (median [IQR] age, 49 [38-58] years; 63 663 [52.1%] male) starting systemic immunomodulatory treatment in the US were included. Treatment for patients with CISDs comprised methotrexate (28 684), tumor necrosis factor α inhibitors (40 965), ustekinumab (12 841), IL-23i (6116), IL-17Ai (9799), dupilumab (7787), or apremilast (16 116). Complete blood cell count was the most common test, performed in 41% (3161/7787) to 69% (19 659/28 684) of individuals before initiation across treatments. Between 11% (889/7787) and 59% (3613/6116) of patients had tuberculosis screening within 6 months before treatment, and 3% (149/4577) to 26% (1559/6097) had updated tests 1 year later. Between 13% (1006/7787) and 41% (16 728/40 965) had hepatitis panels before treatment. Low pretreatment testing levels before apremilast (15% [2331/16 116] to 45% [7253/16 116]) persisted a year into treatment (9% [816/8496] to 36% [2999/8496]) and were similar to dupilumab (11% [850/7787] to 41% [3161/7787] vs 3% [149/4577] to 25% [1160/4577]).</jats:p></jats:sec><jats:sec id="ab-dbr230025-9"><jats:title>Conclusions and Relevance</jats:title><jats:p>In this descriptive analysis of patients with CISDs starting systemic immunomodulatory treatment in the US, less than 60% received the recommended pretreatment testing. Additional research is required to understand whether variations in testing affect patient outcomes.</jats:p></jats:sec>

Real-world trends in biologic, oral systemic, and phototherapy in US patients with psoriasis or psoriatic arthritis.

Screening for tuberculosis infection prior to initiation of anti-TNF therapy.

Graphical depiction of longitudinal study designs in health care databases.

Ann Intern Med

Reproducibility of real-world evidence studies using clinical practice data to inform regulatory and coverage decisions.

Nat Commun

Emulation of randomized clinical trials with non-randomized database analyses: results in 32 clinical trials.

JAMA

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies.

European guideline (EuroGuiDerm) on atopic eczema: part I—systemic therapy.

Laboratory testing for the presence of tuberculosis, hepatitis, and other conditions before starting most systemic immunomodulatory agents is recommended in patients with chronic inflammatory skin diseases (CISD) but current testing patterns in the US are unclear.
To determine the prevalence of pretreatment testing that is recommended for patients with CISD (psoriasis, hidradenitis suppurativa, or atopic dermatitis).
This descriptive analysis of US commercial insurance claims databases from December 31, 2002, to December 31, 2020, included adult patients with CISD (psoriasis, hidradenitis suppurativa, or atopic dermatitis) who started an immunomodulatory agent, including methotrexate, tumor necrosis factor α inhibitors, interleukin (IL)-17Ai, ustekinumab, IL-23i, dupilumab, or apremilast.
The proportion of patients who underwent the screening tests as suggested by professional societies-including for tuberculosis, hepatitis, and liver function; complete blood cell counts; and lipid panels-were determined within 6 months before and during 2 years after treatment start.
A total of 122 308 patients with CISDs (median [IQR] age, 49 [38-58] years; 63 663 [52.1%] male) starting systemic immunomodulatory treatment in the US were included. Treatment for patients with CISDs comprised methotrexate (28 684), tumor necrosis factor α inhibitors (40 965), ustekinumab (12 841), IL-23i (6116), IL-17Ai (9799), dupilumab (7787), or apremilast (16 116). Complete blood cell count was the most common test, performed in 41% (3161/7787) to 69% (19 659/28 684) of individuals before initiation across treatments. Between 11% (889/7787) and 59% (3613/6116) of patients had tuberculosis screening within 6 months before treatment, and 3% (149/4577) to 26% (1559/6097) had updated tests 1 year later. Between 13% (1006/7787) and 41% (16 728/40 965) had hepatitis panels before treatment. Low pretreatment testing levels before apremilast (15% [2331/16 116] to 45% [7253/16 116]) persisted a year into treatment (9% [816/8496] to 36% [2999/8496]) and were similar to dupilumab (11% [850/7787] to 41% [3161/7787] vs 3% [149/4577] to 25% [1160/4577]).
In this descriptive analysis of patients with CISDs starting systemic immunomodulatory treatment in the US, less than 60% received the recommended pretreatment testing. Additional research is required to understand whether variations in testing affect patient outcomes.

Prevalence of Pretreatment Testing Recommended for Patients With Chronic Inflammatory Skin Diseases.

Prevalence of Pretreatment Testing Recommended for Patients With Chronic Inflammatory Skin Diseases

<jats:sec id="ab-doi230059-4"><jats:title>Importance</jats:title><jats:p>Biologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk factors for this are unknown.</jats:p></jats:sec><jats:sec id="ab-doi230059-5"><jats:title>Objective</jats:title><jats:p>To explore risk of paradoxical eczema by biologic class and identify factors associated with paradoxical eczema.</jats:p></jats:sec><jats:sec id="ab-doi230059-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This prospective cohort study used data from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis who were seen at multicenter dermatology clinics in the UK and Ireland. Included participants were registered and had 1 or more follow-up visits between September 2007 and December 2022.</jats:p></jats:sec><jats:sec id="ab-doi230059-7"><jats:title>Exposures</jats:title><jats:p>Duration of exposure to tumor necrosis factor (TNF) inhibitors, interleukin (IL) 17 inhibitors, IL-12/23 inhibitors, or IL-23 inhibitors until paradoxical eczema onset, treatment discontinuation, last follow-up, or death.</jats:p></jats:sec><jats:sec id="ab-doi230059-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Incidence rates of paradoxical eczema, paradoxical eczema risk by biologic class, and the association of demographic and clinical variables with risk of paradoxical eczema were assessed using propensity score–weighted Cox proportional hazards regression models.</jats:p></jats:sec><jats:sec id="ab-doi230059-9"><jats:title>Results</jats:title><jats:p>Of 56 553 drug exposures considered, 24 997 from 13 699 participants were included. The 24 997 included exposures (median age, 46 years [IQR, 36-55 years]; 57% male) accrued a total exposure time of 81 441 patient-years. A total of 273 exposures (1%) were associated with paradoxical eczema. The adjusted incidence rates were 1.22 per 100 000 person-years for IL-17 inhibitors, 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors. Compared with TNF inhibitors, IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39; 95% CI, 0.19-0.81), and there was no association of IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16) with risk of paradoxical eczema. Increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03) and history of AD (HR, 12.40; 95% CI, 6.97-22.06) or hay fever (HR, 3.78; 95% CI, 1.49-9.53) were associated with higher risk of paradoxical eczema. There was a lower risk in males (HR, 0.60; 95% CI, 0.45-0.78).</jats:p></jats:sec><jats:sec id="ab-doi230059-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>In this study, in biologic-treated patients with psoriasis, paradoxical eczema risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema. The overall incidence of paradoxical eczema was low. Further study is needed to replicate these findings.</jats:p></jats:sec>

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Biologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk factors for this are unknown.
To explore risk of paradoxical eczema by biologic class and identify factors associated with paradoxical eczema.
This prospective cohort study used data from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis who were seen at multicenter dermatology clinics in the UK and Ireland. Included participants were registered and had 1 or more follow-up visits between September 2007 and December 2022.
Duration of exposure to tumor necrosis factor (TNF) inhibitors, interleukin (IL) 17 inhibitors, IL-12/23 inhibitors, or IL-23 inhibitors until paradoxical eczema onset, treatment discontinuation, last follow-up, or death.
Incidence rates of paradoxical eczema, paradoxical eczema risk by biologic class, and the association of demographic and clinical variables with risk of paradoxical eczema were assessed using propensity score-weighted Cox proportional hazards regression models.
Of 56 553 drug exposures considered, 24 997 from 13 699 participants were included. The 24 997 included exposures (median age, 46 years [IQR, 36-55 years]; 57% male) accrued a total exposure time of 81 441 patient-years. A total of 273 exposures (1%) were associated with paradoxical eczema. The adjusted incidence rates were 1.22 per 100 000 person-years for IL-17 inhibitors, 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors. Compared with TNF inhibitors, IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39; 95% CI, 0.19-0.81), and there was no association of IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16) with risk of paradoxical eczema. Increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03) and history of AD (HR, 12.40; 95% CI, 6.97-22.06) or hay fever (HR, 3.78; 95% CI, 1.49-9.53) were associated with higher risk of paradoxical eczema. There was a lower risk in males (HR, 0.60; 95% CI, 0.45-0.78).
In this study, in biologic-treated patients with psoriasis, paradoxical eczema risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema. The overall incidence of paradoxical eczema was low. Further study is needed to replicate these findings.

Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis.

Risk of Paradoxical Eczema in Patients Receiving Biologics for Psoriasis

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