Focus on Psoriasis

A report from the 2020 Virtual EADV Congress

By Thomas Scharnitz, MD 

Held as a virtual event this year due to the COVID-19 pandemic, the 29th Congress of the EADV hosted nearly 11,000 attendees logging in from all over the world. Psoriasis played an important role in the EADV agenda, according to conference planners, in recognition that the disease affects 2-3% of the world's population.

The EADV virtual congress featured sessions on psoriasis genetics and pathophysiology as well as presentations on promising therapies, from "classical treatments to small molecules," psoriasis and pregnancy, biologics and the treatment of cardiovascular inflammation, and more.

The following are summaries of the EADV sessions with a focus on psoriasis.  

GENERAL SESSIONS

• Psoriasis: A Systemic Disease
• Psychological Burden of Psoriasis
• Psoriasis: Classical vs. Paradoxical
• SARS-CoV-2 (COVID-19) Pandemic and Psoriasis Management
  

PEDIATRIC PSORIASIS

• The Use of Biologics in Children
• Secukinumab in Pediatric Psoriasis: Results from Two Phase 3 Trials
• Controversies: Phototherapy in Children

Psoriasis Therapeutics

• When to Use Classical Systemic Treatment
• Targeting IL17 and IL23
• How to Deal With the Forest of Biologics in Psoriasis
• Controversies: Can We Stop Biologics in Complete Responders?

Late Breaking

• Efficacy and Safety of Mirikizumab Versus Secukinumab and Placebo in the Treatment of Moderate-to-severe Psoriasis: 52-week results from OASIS-2, a Multicenter, Randomized, Double-blind Study
• A Phase 2B, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Assessing the Efficacy, Safety, and Tolerability of Sonelokinab (M1095), an IL-17A/F Nanobody, in Patients with Moderate-to-severe Chronic Plaque Psoriasis: Results from 24 Weeks
• Results From RIST4721-201, a Randomized, Double-Blind, Placebo Controlled Exploratory Phase 2a Study in Subjects with Palmoplantar Pustulosis
• Tapinarof Cream 1% Once Daily for the Treatment of Plaque Psoriasis: Efficacy and Safety in Two Pivotal Phase 3 Trials

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GENERAL SESSIONS

Psoriasis: A Systemic Disease
Presented by Paolo Gisondi, MD 

Psoriasis patients have an increased risk of systemic inflammatory disorders. Though the exact pathophysiology remains unclear, there are many overlapping risk genes between psoriasis and these metabolic conditions.

 

Psoriatic inflammatory mediators from both the Th1 and Th17 pathways could exert systemic effects on liver, adipose tissue, and skeletal muscle. This in turn may upregulate tissue-specific inflammation, contributing to endothelial dysfunction and ultimately atherosclerotic plaque instability. A striking visual representation was demonstrated in studies in which PET-CT performed on psoriasis patients exhibited foci of inflammation in the aorta and various other tissues.^1,2

 

Studying this link between psoriasis, obesity, and cardiovascular disease, Dr. Gisondi found that adipocytokines mediate crosstalk between skin and adipose tissue, and that both adipocytes and CRP are significantly increased in psoriasis.³  Further, he found that non-alcoholic fatty liver disease (NAFLD) is frequent in psoriasis (48% vs 25% controls) and correlates with worsening PASI score. He suggests that increased release of IL-6, TNF-α, and adipocytokines may drive this NAFLD.^4,5

 

Like metabolic comorbidities, the development of psoriatic arthritis (PsA) is mediated by genetics, immunology, and the environment. Though PsA can develop insidiously, imaging can detect PsA prior to symptom development.⁶ Using ultrasound, Dr. Gisondi found that even asymptomatic patients display entheseal abnormalities, and that quadriceps tendon thickness is an independent predictor of PsA development.^7-8

 

Given this self-perpetuating inflammatory loop in psoriasis, the metabolic syndrome, cardiovascular disease, and PsA, Dr. Gisondi hypothesizes that early intervention could mitigate or even abate the development of such comorbidities, and therefore further studies are essential.^9,10

 

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GENERAL SESSIONS

Psychological Burden of Psoriasis
Presented by Dimitrios Ioannides, MD, PhD

Psoriasis is a major global health problem and has an immense impact on patients’ lives. Unfortunately, many patients suffer needlessly due to delayed diagnosis, delayed treatment, or under-treatment.11

Increasingly, studies have demonstrated the negative psychological impact of psoriasis. Most psoriasis patients experience stigmatization, discrimination, and humiliation, and the emotional impact is not always proportional to disease extent. In addition to negative self-perception, defined psychiatric diagnoses are more prevalent in psoriasis patients.12-14

A large meta-analysis found that over half of patients suffer from some diagnoseable psychiatric disorder,15 and a case-controlled study identified a bidirectional association between psoriasis and depression.16 Another study found significant increase in relative risk (RR) for depression (1.39), anxiety (1.21), and suicidality (1.44), with depression RR higher in severe (1.72) compared to mild (1.38) psoriasis. Moreover, younger patients seem to be more affected.17

Interestingly, psoriatic skin lesions are not the only factor in depression; the ‘inflammatory state’ of psoriasis also contributes directly. Pro-inflammatory cytokines cause changes in neurotransmitter signaling,18 and shared psoriasis/depression cytokines such as IFN-a and IL-2 induce enzymatic degradation of tryptophan, a serotonin precursor. Furthermore, these tryptophan catabolites can independently induce depression and anxiety.19

Early detection of depression can be reliably achieved through short, effective screening techniques,20,21 and prompt effective treatment may prevent depressive symptoms.22 Dr. Ioannides stressed that integrated, comprehensive treatment for our patients is necessary to improve all facets of their lives.

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GENERAL SESSIONS

Psoriasis: Classical vs Paradoxical
Presented by Curdin Conrad, MD

Since their approval, TNF-α blockers have remained a vital treatment for many inflammatory conditions. However, some patients develop a characteristic psoriasiform rash on therapy, deemed ‘paradoxical psoriasis’.

Dr. Conrad studied this TNF-inhibitior (TNFi) induced paradoxical psoriasis in patients, and found that paradoxical psoriasis: is a class effect of all TNFi, is selective for TNFi, is a side effect of TNFi (it is not de novo psoriasis), and resolves when switching to alternate class. Comparing several psoriasis cytokines, his team found a massive accumulation of plasmacytoid dendritic cells (pDCs) with ensuing Type-1 interferon (IFN-α) overexpression in paradoxical psoriasis compared to classical psoriasis.

In vitro models demonstrated that TNF-blockade on activated pDCs induces IFN-α production, whereas adding back TNF-α significantly decreased production. Similarly, in vivo tape-stripping mouse models revealed transient pDC influx and IFN-α production, and subsequent TNF-blockade prolonged this response. After 7 days TNF-blockade mice had a psoriasiform phenotype, but when IFN-α was also blocked this phenotype resolved.

These data suggest that TNF- α controls the expression of IFN from pDCs via a negative feedback loop, and that paradoxical psoriasis has complete dependence on IFN-α. Additionally, T-cells were not required to induce this psoriasiform rash in mice; CD8+ intraepidermal T-cells are were almost non-existent, in stark comparison to classical psoriasis.23

In summary, paradoxical and classical psoriasis are quite different despite clinical similarity. Importantly, paradoxical psoriasis completely resolves when switching from TNF-blockade to another class, and there is potential for future anti-IFN therapeutics.

Section Pearls:

• Psoriasis is a systemic inflammatory state. Early intervention with biologics may prevent or diminish the development of metabolic, cardiovascular, and arthritis comorbidities.
• Psoriasis patients are at increased risk for depression, anxiety, and suicidality regardless of disease extent. Young and severely affected patients are at higher risk. Early recognition and psoriasis treatment may prevent depressive symptoms.
• Despite clinical similarity to classical psoriasis, TNF-blockade induced “paradoxical psoriasis” is a distinct entity. Paradoxical psoriasis is a class effect of all TNF-inhibitors, and drug cessation or switching to another medication class resolves the rash. 

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GENERAL SESSIONS

SARS-CoV-2 (COVID-19) Pandemic and Psoriasis Management

The SARS-CoV-2 (COVID-19) pandemic has had a sweeping global impact on all facets of medicine and has fundamentally changed the way we monitor and treat patients. This has raised serious safety questions in psoriasis management, specifically regarding systemic and biologic medications. The EADV speakers confronted this critical issue by reviewing the evolving international data.

Giovanni Damiani, MD, of Milan, Italy reviewed the pathophysiology of COVID-19 infection, including the resulting immune cytokine storm which increases risk of severe complications and mortality. In an Italian multicenter case-control study reviewing teledermatology and in-person visits of 1193 psoriasis patients from February 21 (first confirmed case) to April 9, 2020, only 1.8% in total were affected by the virus, with 1.4% (n = 17) quarantined at home and only 0.4% (n = 5) hospitalized. Importantly, no patients died. Key confounders included obesity and/or smoking in most patients. Though patients under biologics and small molecules demonstrated higher risk of infection and hospitalization, there was no increased risk of ICU admission or death. No patients under apremilast treatment were infected. Dr. Damiani hypothesized that immunosuppressives may provide a protective effect against the cytokine storm and resulting COVID-19 morbidity and mortality.¹

Anne-Claire Fougerousse, MD, of Saint Mandé, France reviewed results from a French multicenter, cross-sectional study of 1418 adult psoriasis patients receiving systemic or biologic treatment (SBT) from April 27 to May 7, 2020. 330 patients were on systemic therapy (mostly methotrexate) and 1005 on biologic therapy. 25% of patients had a risk factor for severe infection (including obesity), and 22% patients on systemic and 14% on biologic stopped therapy during the pandemic. Of the 54 patients who contracted COVID-19, only 5 required hospitalization, 2 required ICU admission, and no patients died; notably 60% (n = 3) were obese, including both patients admitted to the ICU. Importantly, there was no observed significant difference in COVID-19 cases when comparing initiation versus maintenance therapy, suggesting that initiating SBT for severe psoriasis during the pandemic may be safe after careful consideration.²

Phyllis Spuls, MD, PhD, of Amstelveen, Netherlands summarized results from the PSOPROTECT registry of 374 COVID-19 cases in psoriasis patients under SBT. Though 93% of patients fully recovered, 21% were hospitalized at some point and 2% died. Increased hospitalization was significantly associated with older age (odds ratio 1.59 per 10 years), male sex (OR 2.51), non-white ethnicity (OR 3.15), and comorbid chronic lung disease (OR 3.87). Hospitalization occurred more in systemics than biologics (OR 2.84), and there was no significant difference between biologic classes.³ Other studies have shown similar results, including Italian studies and the large SECURE-IBD registry of 3500+ patients.^1,4,5 In this registry, hospitalization rate was higher for conventional systemic vs biologics, and death occurred more frequently in systemic corticosteroids (9%) and methotrexate (5%, though n = 1) than biologics (roughly 0.5% for both anti-TNF, anti-IL12/23).⁵

In accordance with all early data, the EADV has released Task Force Recommendations. In summary: in patients with active infection: conventional systemics, JAK inhibitors, and biologics should be stopped until more data has been collected. In uninfected/healthy patients, IL-17, IL-23, apremilast, and acitretin are likely safe to initiate and continue, and physicians should consider switching from other therapies to these safer alternatives.⁶

Section Pearls:

• Though COVID-19 infection rates appear higher in psoriasis patients on biologic or small molecule therapy, immunosuppressive treatments may be protective against the subsequent inflammatory cytokine storm (and therefore severe infection) in COVID-19.
• Patients who are initiating systemic and biologic therapy during the pandemic do not seem to be at significantly higher risk for infection than those patients on maintenance therapy.
• Non-biologic systemic therapies convey increased risk of severe complications when compared to biologics. Apremilast, acitretin, and IL-17/IL-23 inhibitors appear safest.

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PEDIATRIC PSORIASIS

The Use of Biologics in Children
Presented by Beatrix Volc-Platzer, MD

To date, our experience and data of biologics comes largely from the adult population. For psoriasis, there are currently four biologics approved for pediatric use: etanercept (6+ years), adalimumab (4+ years), ustekinumab (12+ years) and secukinumab (6+ years).

Overall, biologics overall appear effective and safe in pediatric psoriasis. Real-world data of anti-TNF agents in children found injection site reactions in roughly 27% and infections in roughly 11%, but notably few severe adverse events overall and none with ustekinumab.^1-3

Children metabolize medications, including biologics, differently and often require a relatively higher dose; drug troughs can ensure safety and efficacy.⁴ Pediatric drug survival is also important. A study evaluating real-life conditions found drug survival is significantly highest for ustekinumab (versus adalimumab and etanercept) across all treatment groups and psoriasis types, and across 8 years approximately 60% of children remained on ustekinumab.

Other considerations in pediatric psoriasis includes biologic effect on comorbidities, immunogenicity, vaccinations, and currently, COVID-19 risk. To date, no reliable data exists on therapeutic effects to comorbidities in the pediatric population,^5,6  and immunogenicity has not been studied extensively.⁷  Though often not an issue in adults, live vaccines are strictly contraindicated and therefore must be completed prior to biologic initiation in children.^8-9  Fortunately, thus far biologics do not appear to increase risk of poor COVID-19 outcomes, though evolving data should continue to be analyzed carefully.

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PEDIATRIC PSORIASIS

Secukinumab in Pediatric Psoriasis: Results from Two Phase 3 Trials
Presented by Nina Magnolo, MD, and Christine Bodemer, MD, PhD

Introduction: Dr. Magnolo and Dr. Bodemer presented data from two Phase 3, Open-label, Multicenter Trials to assess the efficacy of subcutaneous secukinumab, a monoclonal antibody against interleukin (IL)-17A, in pediatric psoriasis. The 12 and 24 week data presented by Dr. Magnolo included historical placebo data used in Bayesian analysis, and the 12 and 52 week data presented by Dr. Bodemer included an etanercept arm and placebo arm.

Design: PASI and IGA(0,1) response in moderate-to-severe chronic plaque psoriasis, age 6-18 years, with monthly low dose (75/75/150mg) and high dose (75/150/300mg) arms based on weight (< 25kg / 25-50kg / ≥ 50kg), after induction dosing. Baseline demographics and disease severity were balanced and comparable across treatment arms.

 

Results: Both studies demonstrated significant superiority to placebo, and Dr. Bodemer’s study demonstrated significant superiority to etanercept in IGA(0,1) and PASI-90.

 

Study presented by Dr. Magnolo, 84 subjects

 

	IGA (0,1)	PASI-75	PASI-90	PASI-100
Week 12: SEC low dose	78.6%	92.9%
Week 12: SEC high dose	83.3%	92.9%
Week 24: SEC low dose	88.1%	95.2%	88.1%	66.7%
Week 24: SEC high dose	92.9%	95.2%	88.1%	66.7%

 

Study presented by Dr. Bodemer, 162 subjects

 

	IGA (0,1)	PASI-75	PASI-90	PASI-100
Week 12: SEC low dose	70.0%	80.0%	72.5%	30.0%
Week 12: SEC high dose	60.0%	77.5%	67.5%	27.5%
Etanercept arm	34.1%	63.4%	29.3%	17.1%
Placebo arm	4.9%	14.6%	2.4%	0.0%
Week 52: SEC low dose	72.5%	87.5%	75.0%	40.0%
Week 52: SEC high dose	75.0%	87.5%	80.0%	47.5%
Etanercept arm	56.1%	68.3%	51.2%	22.0%
Placebo arm - Placebo crossover to secukinumab (week 12) response was comparable to secukinumab treatment arms

Adverse events: Majority of AEs in both studies were mild to moderate, with few severe AEs and no deaths. Candida infections occurred in roughly 1-2% of patients in both studies.

Conclusion: Secukinumab appears highly effective and safe in pediatric patients, with rapid and durable response. The safety profile is consistent with the known safety profile from adult studies.

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PSORIASIS THERAPEUTICS

Controversies: Phototherapy in Children

Presented by Dr. Chiara Cortelazzi, MD, and Marina Venturini, MD

Phototherapy is commonly used in adult psoriasis, but is phototherapy safe and effective in children?

 

YES: Dr. Cortelazzi argued that narrowband UVB (nbUVB) therapy is appropriate for most children with psoriasis, though no set guidelines exist. Psoralen/UVA (PUVA), though, should be avoided unless in severe or refractory disease, given known long-term risk of carcinogenesis and cataracts (the ocular lens is more permeable in young).

nbUVB protocols vary, but the typical starting dose in children is ≤ 70% of minimal erythema dose (MED), which may be increased gradually by 10-20% per session.^10-11  Frequency and duration of treatment vary, but Dr. Cortelazzi generally performs 2-3 sessions per week for several months.

In psoriasis, nbUVB is considered a first-line treatment diffuse disease,¹²  and was effective and safe in retrospective study of 88 pediatric psoriasis patients; 51% of children given nbUVB had full clearance, and 92% achieved greater than 75% improvement.¹³  Adjunct topical therapies, applied after nbUVB sessions, enhance efficacy. If the patient cannot reach the clinic or hospital, home units or supervised natural sunlight for 10-15 minutes can also be considered.

NO: Dr. Venturini opposed phototherapy in children, primarily because overall data on safety and efficacy are limited as RCTs are lacking. Appropriate patient selection is vital, and absolute contraindications include photosensitivity and cancer-predisposing genodermatoses.

Aside from known acute cutaneous adverse events (AEs), young children often exhibit poor eyewear compliance and may experience anxiety. Long-term AEs remain unknown. Though no relationship between nbUVB and skin cancer has yet been detected,^14,15 children may require extended nbUVB treatment and additional immunosuppressives, confounding the theoretical risk. PUVA clearly carries higher risk of non-melanoma skin cancer and cataracts, and therefore should be approached with extreme caution.^14-16

Interestingly, there are reports of increased dysplastic melanocytic nevi occurring in neonatal blue light therapy (spectrum adjacent to UV light) treating neonatal hyperbilirubinemia, highlighting the potential risk of phototherapy.¹⁷ Overall, true carcinogenic potential with repeat UV exposure remains unclear and there may be a significant delay from treatment initiation to carcinogenesis.

In summary, both Dr. Cortelazzi and Dr. Venturini agree that extra caution and individualized risk assessments are important in children, and phototherapy should be considered only after weighing all risks and benefits.

 

SECTION PEARLS:

• Though much of our data comes from adult populations and studies, approved biologics appear safe when used in pediatric psoriasis, even during the COVID-19 pandemic.
• Phase 3 trials of secukinumab, both low and high dose, demonstrate safety and efficacy in pediatric psoriasis, with rapid and durable PASI-75 response exceeding 85%.
• Though nbUVB appears safe and effective for children with psoriasis, no randomized control trials exist. Careful patient selection and individualized treatment plans are required.

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PSORIASIS THERAPEUTICS

When to Use Classical Systemic Treatment
Presented by Rolland Gyulai, MD, PhD 

Use of classical systemic medications in psoriasis has been decreasing, largely due to biologics and subsequent increased expectation from both patients and dermatologists.¹ 

Methotrexate (MTX) is widely used and effective, as nearly 42% of patients achieve PASI-75 response on 10-15mg/week dosing, and roughly 50% when dose is intensified to 22.5mg/week.^2,3 Given known side effects, careful patient selection is crucial. Dr. Gyulai’s team demonstrated that BMI correlates with liver elastography “fibroscan score,” suggesting obesity is a risk factor, but interestingly cumulative MTX dose does not correlate.4 Subcutaneous injection and closely following guidelines can mitigate risk. Additionally, new data suggest that MTX is immunomodulatory as it restores function of peripheral regulatory T-cells, and that it also exhibits and inhibitory effect on the JAK/STAT pathway.^4-6

Acitretin as monotherapy can be quite effective when appropriately dosed, with PASI-50/75 response nearing 90% and 66%, but such therapeutic doses approaching 50mg daily are not routinely prescribed.^8,9 Interestingly, gene polymorphisms are associated with responsiveness, which could predict for future responders.¹⁰

Less utilized systemics still also play a role in psoriasis, with notable limitations. Cyclosporine can be used safely in the short-term and provides a rapid response; however, response is often short lived as approximately 50% of patients lose efficacy around week 12 in real world databases.¹¹ Fumaric acid exhibits efficacy is similar to MTX (PASI-50 in 64%, PASI-75 in

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PSORIASIS THERAPEUTICS

Targeting IL17 and IL23
Presented by Curdin Conrad, MD

The IL-17 and IL-23 targeting biologics have transformed psoriasis management and continue to set new standards in cutaneous clearance, durable response, and safety.

IL-17 blockade demonstrates excellent PASI response across many trials, and response is quite long-lasting. Secukinumab achieves exceptional PASI-90/100 response (76.2% and 45.9%) through 52 weeks, and results are similar for other IL-17 drugs.¹⁴ Early selection of appropriate IL-17 agents is also vital for drug survival. Egeberg, et al., showed that more than 80% of bionaive patients remain on secukinumab after 3 years, compared to only 50% and 33% with one or two plus prior biologics, respectively.¹⁵

Anti-IL-23p19 drugs have pushed clearance even further. For example, risankizumab demonstrated PASI-100 response in 58% in both treatment and placebo crossover arms.¹⁶ Another major benefit of the IL-23 blockade is sustained and apparent disease-altering response approaching 6 months, which is considerably longer time than the half-life of these drugs.

When choosing between classes, some factors should be considered. Though the anti-IL-23p19 drugs have higher response rates, ixekizumab and secukinumab (IL-17) both exhibit more rapid clearance than guselkumab (IL-23p19) across the first 20 weeks.^17,18 Additionally, IL-17 blockade shows considerable promise in psoriatic arthritis (PsA), with ACR50 arthritis improvement equivalent or superior to adalimumab in some trials.^19,20

A major reason for choosing against IL-17 drugs is inflammatory bowel disease (IBD). IBD unmasking or flare occurs as anti-IL-17 targets both subsets of Th17 cells, the pathogenic (inflammation, due to IL-17 and IL-22) and non-pathogenic (barrier function, due to IL-17 and IL-10). The IL-23 therapies block only stimulation of pathogenic T-cells, reducing inflammation but sparing some IL-17 for intestinal barrier repair and flora control.^21,22

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PSORIASIS THERAPEUTICS

How to Deal With the Forest of Biologics in Psoriasis
Presented by Christopher Griffiths, OBE, MD, FRCP, FMedSci

With an ever-enlarging armamentarium of biologic treatments, considering each individual patient and collecting real-world data is of utmost importance in achieving optimal, personalized therapies.

TNF-inhibitors (TNFi) have long-term efficacy and safety profiles, and biosimilars now increase the scope of use across specialties. Key considerations prior to treatment include TB status, demyelinating disease, cardiac failure, infection, and antidrug antibodies. Notably, TNFi remain the gold standard for psoriatic arthritis (PsA), and certolizumab can be used in pregnancy.

Newer biologics carry lower risk of infections and exhibit increased PASI response, but often lack extensive real-world data. Anti-IL-17 drugs including ixekizumab, secukinumab, and brodalumab (the only IL-17 receptor inhibitor) have excellent PASI-90 response, often exceeding 70%. Importantly, this class succeeds after TNFi failure and is effective in spondyloarthropathy and PsA. Adverse effects (AEs) are often mild-moderate, but candida and IBD exacerbation are important known AEs. Of note, there is an uncertain association between brodalumab and suicidality.

Anti-IL-23 includes ustekinumab (IL-23p40) and the newer, more effective anti-IL-23p19 medications risankizumab, guselkumab, and tildrakizumab. These p19 drugs demonstrate exceptional PASI-90 response of 70-80% and PASI-100 often reaching 50%. They are also disease modifying; one injection may lead to remission. Trials have shown no consistent disconcerting AEs, and unlike anti-IL-17, there carry no candidiasis or IBD risk.

With this vast array of options, Dr. Griffiths emphasizes that the future is targeted therapy. As examples, adalimumab serum levels ≥ 7 µg/mL can achieve excellent PASI-75 response in 81% of patients, and ustekinumab has higher PASI-90 response if the patient is HLA-Cw6+.^23-24 Using large databases and Drug Endotypes (signatures), we continue gaining vital knowledge to predict who is the right candidate for each drug. 

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PSORIASIS THERAPEUTICS

Controversies: Phototherapy in Children
Presented by Dr. Chiara Cortelazzi, MD, and Marina Venturini, MD

Phototherapy is commonly used in adult psoriasis, but is phototherapy safe and effective in children?

YES: Dr. Cortelazzi argued that narrowband UVB (nbUVB) therapy is appropriate for most children with psoriasis, though no set guidelines exist. Psoralen/UVA (PUVA), though, should be avoided unless in severe or refractory disease, given known long-term risk of carcinogenesis and cataracts (the ocular lens is more permeable in young).

nbUVB protocols vary, but the typical starting dose in children is ≤ 70% of minimal erythema dose (MED), which may be increased gradually by 10-20% per session.^10-11  Frequency and duration of treatment vary, but Dr. Cortelazzi generally performs 2-3 sessions per week for several months.

In psoriasis, nbUVB is considered a first-line treatment diffuse disease,¹²  and was effective and safe in retrospective study of 88 pediatric psoriasis patients; 51% of children given nbUVB had full clearance, and 92% achieved greater than 75% improvement.¹³  Adjunct topical therapies, applied after nbUVB sessions, enhance efficacy. If the patient cannot reach the clinic or hospital, home units or supervised natural sunlight for 10-15 minutes can also be considered.

NO: Dr. Venturini opposed phototherapy in children, primarily because overall data on safety and efficacy are limited as RCTs are lacking. Appropriate patient selection is vital, and absolute contraindications include photosensitivity and cancer-predisposing genodermatoses.

Aside from known acute cutaneous adverse events (AEs), young children often exhibit poor eyewear compliance and may experience anxiety. Long-term AEs remain unknown. Though no relationship between nbUVB and skin cancer has yet been detected,^14,15 children may require extended nbUVB treatment and additional immunosuppressives, confounding the theoretical risk. PUVA clearly carries higher risk of non-melanoma skin cancer and cataracts, and therefore should be approached with extreme caution.^14-16

Interestingly, there are reports of increased dysplastic melanocytic nevi occurring in neonatal blue light therapy (spectrum adjacent to UV light) treating neonatal hyperbilirubinemia, highlighting the potential risk of phototherapy.¹⁷ Overall, true carcinogenic potential with repeat UV exposure remains unclear and there may be a significant delay from treatment initiation to carcinogenesis.

In summary, both Dr. Cortelazzi and Dr. Venturini agree that extra caution and individualized risk assessments are important in children, and phototherapy should be considered only after weighing all risks and benefits.

 

SECTION PEARLS:

• Though much of our data comes from adult populations and studies, approved biologics appear safe when used in pediatric psoriasis, even during the COVID-19 pandemic.
• Phase 3 trials of secukinumab, both low and high dose, demonstrate safety and efficacy in pediatric psoriasis, with rapid and durable PASI-75 response exceeding 85%.
• Though nbUVB appears safe and effective for children with psoriasis, no randomized control trials exist. Careful patient selection and individualized treatment plans are required.

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LATE BREAKING

Efficacy and Safety of Mirikizumab Versus Secukinumab and Placebo in the Treatment of Moderate-to-sever Psoriasis: 52-week results from OASIS-2, a Multicenter, Randomized, Double-blind Study

Presented by Kim A. Papp, MD, PhD 

Intro and design: Mirikizumab is a humanized monoclonal antibody that binds the IL-23-p19 subunit. This study assessed PASI-90 and sPGA(0,1) responses of mirikizumab (MIR) q4weeks (induction) then q8weeks (maintenance), versus placebo and secukinumab (SEC) standard dosing

	MIR 250mg	SEC 300mg	Placebo	MIR 125mg
PASI-90 / PASI-100 response
Week 16	74.4% / 37.7%	72.8% / 36.6%	6.3%
Week 52	82.4% / 58.8%	69.4% / 42.9%		81.4% / 53.9%
sPGA response
Week 16	79.5%	76.3%	6.3%
Week 52	83.3%	68.5%		83.1%

 

Adverse events: Similar across treatment arms, most mild-moderate. More major adverse cardiovascular events and 1 death (myocardial infarction) occurred in mirikizumab arms.

Conclusion: Mirikizumab demonstrated superiority to both placebo and secukinumab at week 16 and 52, with durable response.

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LATE BREAKING

A Phase 2B, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Assessing the Efficacy, Safety, and Tolerability of Sonelokinab (M1095), an IL-17A/F Nanobody, in Patients with Moderate-to-severe Chronic Plaque Psoriasis: Results from 24 Weeks 

Presented by Kim A. Papp, MD, PhD

Intro and design: Sonelokinab is an IL-17 A/F nanobody. This study assessed PASI-90 and IGA(0,1) response of sonelokinab at various doses and schedules, versus placebo and secukinumab

Results: For sonelokinab, PASI-90 response was achieved in approximately 33% (week 4) and 80% (week 12) and was sustained to week 24.

PASI-100 was achieved by roughly 50% by week 24. IGA 0,1 response in approximately 80% (week 12) and was sustained in responders to week 24. Secukinumab showed similar response, but sonelokinab response was more rapid.

Adverse effects: Non-serious oral candidiasis occurred with IL-17 blockade. There were few serious AEs, no major adverse cardiovascular events, and no deaths at week 24.

Conclusion: Sonelokinab appears promising, with rapid and durable response.

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LATE BREAKING

Results From RIST4721-201, a Randomized, Double-Blind, Placebo Controlled Exploratory Phase 2a Study in Subjects with Palmoplantar Pustulosis

Presented by Robert Bissonnette MD, FRCPC

Intro and design: RIST4721 is an oral small molecule CXC chemokine receptor 2 (CXCR2) antagonist. This study assessed RIST4721 300mg daily vs placebo in palmoplantar psoriasis, with primary endpoint of change from baseline in fresh pustules and total pustules at week 4.

Results: Primary endpoint was not significant, but post-HOC analysis in subgroup with progressing disease showed statistically significant results (p < 0.05) as follows:

• PPPASI 50% reduction: achieved by 71% in RIST (n = 5/7) vs 15% in placebo (n = 2/13)
• Target palm or sole pustule count; -29.0 in RIST (n = 7) vs -3.5 in placebo (n= 13)
• Significant pharmacodynamic results in RIST arm included: decrease in circulating neutrophils, decrease in T-cell activation markers, and increase in IL-8 levels.

Adverse effects: More treatment emergent AEs in RIST than placebo (86.7% vs 36.8%); most were mild (mainly gastrointestinal or musculoskeletal), with no severe AEs or deaths Conclusion: RIST is a potent small molecule CXCR2 antagonist with potential as novel oral treatment for neutrophil diseases; further studies are needed to assess its potential efficacy.

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LATE BREAKING

Tapinarof Cream 1 Percent Once Daily for the Treatment of Plaque Psoriasis: Efficacy and Safety in Two Pivotal Phase 3 Trials
Presented by Mark Lebwohl, MD

Intro and design: Two identical randomized, vehicle-controlled studies of tapinarof, a first-in-class, non-steroidal topical aryl hydrocarbon receptor modulating agent (TAMA). This study assessed PGA(0,1) and PASI-75 response in adults aged 18-75 with predominantly moderate psoriasis

Results: At week 12 both endpoints achieved, all outcomes with p < 0.0001:

• Primary endpoint, PGA(0,1): 35.4% / 40.2% (tapinarof) vs 6.0% / 6.3% (vehicle)
• Secondary Endpoint, PASI-75 response: 36.1% / 47.6% (tapinarof) vs 10.2% / 6.9% (vehicle).

Adverse effects: Most were mild-moderate. Discontinuation rate 5.6% and 5.8% in tapinarof arms, due to folliculitis (1.8% and 0.9%), contact dermatitis (1.5% and 2.0%), headache (0.3% and 0.6%). Conclusion: Tapinarof cream demonstrates significant, clinically meaningful efficacy, and has the potential to be the first TAMA treatment option for psoriasis.

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