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 id="ab-doi250005-4"><jats:title>Importance</jats:title><jats:p>Systemic treatments for psoriatic disease affect the immune system and may increase infection risk. Older adults are at high risk for infection, and the relative safety of systemic treatments for them is unknown.</jats:p></jats:sec><jats:sec id="ab-doi250005-5"><jats:title>Objective</jats:title><jats:p>To evaluate the association of systemic treatments for psoriatic disease with rates of serious infection among older adults.</jats:p></jats:sec><jats:sec id="ab-doi250005-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This cohort study used linked population-based health administrative data from 2002 to 2021 in Ontario, Canada. Participants included Ontario residents 66 years and older with psoriatic disease who were dispensed their first systemic medication between April 1, 2002, and December 31, 2020. Data were analyzed between November 2021 and August 2024.</jats:p></jats:sec><jats:sec id="ab-doi250005-7"><jats:title>Exposure</jats:title><jats:p>Time-varying use of systemic medications categorized as (1) methotrexate; (2) other older systemic medications; (3) anti–tumor necrosis factor (anti-TNF) biologics; (4) other biologics (targeting interleukin [IL]-12, IL-23, and IL-17); and (5) tofacitinib.</jats:p></jats:sec><jats:sec id="ab-doi250005-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>The main outcome was time to serious infection, defined as hospitalization for any infectious cause occurring up to March 2021. Multivariable Andersen-Gill recurrent event regression was used to estimate the association between each medication category and serious infection rates. The relative rates (RRs) of serious infection with 95% CIs for time actively using each medication category vs time not using that medication category were calculated.</jats:p></jats:sec><jats:sec id="ab-doi250005-9"><jats:title>Results</jats:title><jats:p>Of 11 641 new users of systemic therapy, 6114 (53%) were female, and the median (IQR) age was 71 (68-76) years. There were 1967 serious infections during a median (IQR) of 4.8 (2.3-8.4) years of follow-up. There were 2.7 serious infections per 100 person-years using methotrexate, 2.5 per 100 person-years using other older systemic drugs, 2.2 per 100 person-years using anti-TNF biologics, 1.4 per 100 person-years using other biologics, and 8.9 per 100 person-years using tofacitinib. In the multivariable-adjusted model, methotrexate (RR, 0.95 [95% CI, 0.85-1.07]), other older systemic medications (RR, 0.92 [95% CI, 0.79-1.07]), and anti-TNF biologics (RR, 0.87 [95% CI, 0.69-1.10]) were not associated with serious infection compared to person-time not using those respective medications. Other biologics (RR, 0.65 [95% CI, 0.48-0.88]) were associated with lower rates of serious infection, whereas tofacitinib (RR, 2.89 [95% CI, 1.14-7.34]) was associated with higher rates of serious infection.</jats:p></jats:sec><jats:sec id="ab-doi250005-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>In this cohort study, biologics targeting IL-12, IL-23, or IL-17 were associated with a lower rate of serious infection among older adults with psoriatic disease. These biologics may have important safety benefits for older adults with higher infection risk.</jats:p></jats:sec>

Trends in the prevalence and incidence of psoriasis and psoriatic arthritis in Ontario, Canada: a population-based study.

Arthritis Care Res (Hoboken)

Canadian burden of skin disease from 1990 to 2017: results from the Global Burden of Disease 2017 study.

J Cutan Med Surg

Special article: 2018 American College of Rheumatology/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis.

Arthritis Rheumatol

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

Predicting risk of adverse drug reactions in older adults.

Ther Adv Drug Saf

Infectious disease hospitalizations: United States, 2001 to 2014.

Chest

Representation of older adults in randomized controlled trials on systemic treatment in plaque psoriasis: a systematic review.

Safety of systemic medications among older adults with psoriasis and atopic dermatitis: a systematic review of observational studies.

Older adults on systemic treatment for psoriasis and risk of infection: a propensity score-matched population-based study.

The reporting of studies conducted using observational routinely collected health data statement for pharmacoepidemiology (RECORD-PE).

Coding accuracy of administrative drug claims in the Ontario Drug Benefit database.

Can J Clin Pharmacol

Socioeconomic misclassification in Ontario’s health care registry.

Can J Public Health

Use of postal codes and addresses in the analysis of health data.

Health Rep

Identification of physician-diagnosed Alzheimer’s Disease and related dementias in population-based administrative data: a validation study using family physicians’ electronic medical records.

J Alzheimers Dis

Identifying diabetes cases from administrative data: a population-based validation study.

BMC Health Serv Res

Detecting chronic kidney disease in population-based administrative databases using an algorithm of hospital encounter and physician claim codes.

BMC Nephrol

Identifying cirrhosis, decompensated cirrhosis and hepatocellular carcinoma in health administrative data: A validation study.

PLoS One

Using the Johns Hopkins Aggregated Diagnosis Groups (ADGs) to predict mortality in a general adult population cohort in Ontario, Canada.

Med Care

Glucocorticoid-induced osteoporosis management among seniors, by year, sex, and indication, 1996-2012.

Osteoporos Int

Cox’s regression model for counting processes: a large sample study.

Ann Stat

Accuracy of Canadian health administrative databases in identifying patients with rheumatoid arthritis: a validation study using the medical records of rheumatologists.

Risk of serious infections in patients with psoriasis on biologic therapies: a systematic review and meta-analysis.

J Invest Dermatol

Comparative short-term risks of infection and serious infection in patients receiving biologic and small-molecule therapies for psoriasis and psoriatic arthritis: a systemic review and network meta-analysis of randomized controlled trials.

Ther Adv Chronic Dis

Serious infections among a large cohort of subjects with systemically treated psoriasis.

Risk of serious infection in patients receiving systemic medications for the treatment of psoriasis.

Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis.

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

Cochrane Database Syst Rev

Systemic treatments for psoriatic disease affect the immune system and may increase infection risk. Older adults are at high risk for infection, and the relative safety of systemic treatments for them is unknown.
To evaluate the association of systemic treatments for psoriatic disease with rates of serious infection among older adults.
This cohort study used linked population-based health administrative data from 2002 to 2021 in Ontario, Canada. Participants included Ontario residents 66 years and older with psoriatic disease who were dispensed their first systemic medication between April 1, 2002, and December 31, 2020. Data were analyzed between November 2021 and August 2024.
Time-varying use of systemic medications categorized as (1) methotrexate; (2) other older systemic medications; (3) anti-tumor necrosis factor (anti-TNF) biologics; (4) other biologics (targeting interleukin [IL]-12, IL-23, and IL-17); and (5) tofacitinib.
The main outcome was time to serious infection, defined as hospitalization for any infectious cause occurring up to March 2021. Multivariable Andersen-Gill recurrent event regression was used to estimate the association between each medication category and serious infection rates. The relative rates (RRs) of serious infection with 95% CIs for time actively using each medication category vs time not using that medication category were calculated.
Of 11 641 new users of systemic therapy, 6114 (53%) were female, and the median (IQR) age was 71 (68-76) years. There were 1967 serious infections during a median (IQR) of 4.8 (2.3-8.4) years of follow-up. There were 2.7 serious infections per 100 person-years using methotrexate, 2.5 per 100 person-years using other older systemic drugs, 2.2 per 100 person-years using anti-TNF biologics, 1.4 per 100 person-years using other biologics, and 8.9 per 100 person-years using tofacitinib. In the multivariable-adjusted model, methotrexate (RR, 0.95 [95% CI, 0.85-1.07]), other older systemic medications (RR, 0.92 [95% CI, 0.79-1.07]), and anti-TNF biologics (RR, 0.87 [95% CI, 0.69-1.10]) were not associated with serious infection compared to person-time not using those respective medications. Other biologics (RR, 0.65 [95% CI, 0.48-0.88]) were associated with lower rates of serious infection, whereas tofacitinib (RR, 2.89 [95% CI, 1.14-7.34]) was associated with higher rates of serious infection.
In this cohort study, biologics targeting IL-12, IL-23, or IL-17 were associated with a lower rate of serious infection among older adults with psoriatic disease. These biologics may have important safety benefits for older adults with higher infection risk.

Systemic Therapies for Psoriatic Disease and Serious Infections in Older Adults.

Systemic Therapies for Psoriatic Disease and Serious Infections in Older Adults

<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>

Psoriasis: classical vs. paradoxical: the yin-yang of TNF and type I interferon.

Biologic agent–associated cutaneous adverse events: a single center experience.

Clin Med Res

Eczematous eruption during anti-interleukin 17 treatment of psoriasis: an emerging condition.

Disease concomitance in psoriasis.

Mutual antagonism of T cells causing psoriasis and atopic eczema.

Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.

Am J Hum Genet

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.

Nat Genet

Can atopic eczema and psoriasis coexist? a systematic review and meta-analysis.

Skin Health Dis

Psoriasiform dermatitis during dupilumab treatment for moderate-to-severe atopic dermatitis in children.

Pediatr Dermatol

Review of dupilumab-associated inflammatory arthritis: an approach to clinical analysis and management.

JAAD Case Rep

The British Association of Dermatologists’ Biologic Interventions Register (BADBIR): design, methodology and objectives.

Risk of serious infection in patients with psoriasis receiving biologic therapies: a prospective cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Regression models and life-tables.

J R Stat Soc B

An introduction to propensity score methods for reducing the effects of confounding in observational studies.

Multivariate Behav Res

The central role of the propensity score in observational studies for causal effects.

Biometrika

Variable selection for propensity score models.

Am J Epidemiol

Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls.

Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: results from a 52-week, open-label, phase 3 study (UNCOVER-J).

J Dermatol

Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled phase IIIb study of patients with moderate-to-severe genital psoriasis.

Efficacy and safety of secukinumab in elderly subjects with moderate to severe plaque psoriasis: a pooled analysis of phase III studies.

Drugs Aging

Secukinumab efficacy and safety in Japanese patients with moderate-to-severe plaque psoriasis: subanalysis from ERASURE, a randomized, placebo-controlled, phase 3 study.

Eczema as an adverse effect of anti-TNFa therapy in psoriasis and other Th1-mediated diseases: a review.

Concurrence of psoriasis vulgaris and atopic eczema in a single patient exhibiting different expression patterns of psoriatic autoantigens in the lesional skin.

Mixed profile of cytokines in paradoxical eczematous eruptions associated with anti-IL-17 therapy.

J Allergy Clin Immunol Pract

Integrated safety analysis of treatment-emergent eczematous reactions in patients with moderate-to-severe psoriasis treated with ixekizumab, etanercept and ustekinumab.

Severe skin lesions cause patients with inflammatory bowel disease to discontinue anti-tumor necrosis factor therapy.

Clin Gastroenterol Hepatol

Predictive factors of eczema-like eruptions among patients without cutaneous psoriasis receiving infliximab: a cohort study of 92 patients.

Dermatology

Atopic polygenic risk score is associated with paradoxical eczema developing in psoriasis patients treated with biologics.

Filaggrin mutations, atopic eczema, hay fever, and asthma in children.

Prevalence and characteristics of atopic dermatitis among young adult females and males—report from the Swedish population-based study BAMSE.

Effects of cyclosporine A on T cell development and clonal deletion.

Science

Inhibitory effects of cyclosporine on human regulatory T cells in vitro.

Transplant Proc

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

Papers