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AVT02 as effective as reference adalimumab in moderate-to-severe plaque psoriasis

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Key clinical point: The biosimilar AVT02 is as efficacious, safe, and immunogenic as its originator, adalimumab, in moderate-to-severe chronic plaque psoriasis.

Major finding: At week 16, AVT02 and originator adalimumab induced comparable percentage improvement in Psoriasis Area Severity Index (91.6% and 89.6%, respectively), with the difference in percentage improvement within the predefined equivalence margins of ±10% (90% CI, −0.76 to 5.29), along with similar safety, tolerability, and immunogenicity profiles, which lasted through week 50.

Study details: This was a phase 3 study including 413 adult patients with moderate-to-severe chronic plaque psoriasis who were initially assigned to receive AVT02 or adalimumab; at week 16, the latter were randomly reassigned to continue receiving adalimumab or switch to AVT02 until week 48.

Disclosures: The study was sponsored by Alvotech Swiss AG. SR Feldman and R Kay disclosed receiving research grants, speaker honoraria, or consultancy fees from various sources, including Alvotech, and some of the authors declared being employees of Alvotech.

Source: Feldman SR et al. BioDrugs. 2021 Oct 16. doi: 10.1007/s40259-021-00502-w.

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Key clinical point: The biosimilar AVT02 is as efficacious, safe, and immunogenic as its originator, adalimumab, in moderate-to-severe chronic plaque psoriasis.

Major finding: At week 16, AVT02 and originator adalimumab induced comparable percentage improvement in Psoriasis Area Severity Index (91.6% and 89.6%, respectively), with the difference in percentage improvement within the predefined equivalence margins of ±10% (90% CI, −0.76 to 5.29), along with similar safety, tolerability, and immunogenicity profiles, which lasted through week 50.

Study details: This was a phase 3 study including 413 adult patients with moderate-to-severe chronic plaque psoriasis who were initially assigned to receive AVT02 or adalimumab; at week 16, the latter were randomly reassigned to continue receiving adalimumab or switch to AVT02 until week 48.

Disclosures: The study was sponsored by Alvotech Swiss AG. SR Feldman and R Kay disclosed receiving research grants, speaker honoraria, or consultancy fees from various sources, including Alvotech, and some of the authors declared being employees of Alvotech.

Source: Feldman SR et al. BioDrugs. 2021 Oct 16. doi: 10.1007/s40259-021-00502-w.

Key clinical point: The biosimilar AVT02 is as efficacious, safe, and immunogenic as its originator, adalimumab, in moderate-to-severe chronic plaque psoriasis.

Major finding: At week 16, AVT02 and originator adalimumab induced comparable percentage improvement in Psoriasis Area Severity Index (91.6% and 89.6%, respectively), with the difference in percentage improvement within the predefined equivalence margins of ±10% (90% CI, −0.76 to 5.29), along with similar safety, tolerability, and immunogenicity profiles, which lasted through week 50.

Study details: This was a phase 3 study including 413 adult patients with moderate-to-severe chronic plaque psoriasis who were initially assigned to receive AVT02 or adalimumab; at week 16, the latter were randomly reassigned to continue receiving adalimumab or switch to AVT02 until week 48.

Disclosures: The study was sponsored by Alvotech Swiss AG. SR Feldman and R Kay disclosed receiving research grants, speaker honoraria, or consultancy fees from various sources, including Alvotech, and some of the authors declared being employees of Alvotech.

Source: Feldman SR et al. BioDrugs. 2021 Oct 16. doi: 10.1007/s40259-021-00502-w.

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Ixekizumab bests secukinumab in the real-world race against psoriasis

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Key clinical point: Compared with secukinumab, ixekizumab concorded with significantly increased adherence rates and decreased nonpersistence, discontinuation, and switching in biologic-experienced patients with psoriasis.

Major finding: After 18 months of follow-up, ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab.

Study details: Findings are from a retrospective observational study consisting of prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411).

Disclosures: The study was supported by Eli Lilly and Company, USA. The lead author declared serving as a scientific advisor/clinical study investigator for various companies including Eli Lilly. Some of the authors are full-time employees or stakeholders of Eli Lilly, and a few others work for an alternative employer, which received compensation from Eli Lilly.

Source: Blauvelt A et al. Dermatol Ther (Heidelb). 2021 Oct 15. doi: 10.1007/s13555-021-00627-4.

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Key clinical point: Compared with secukinumab, ixekizumab concorded with significantly increased adherence rates and decreased nonpersistence, discontinuation, and switching in biologic-experienced patients with psoriasis.

Major finding: After 18 months of follow-up, ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab.

Study details: Findings are from a retrospective observational study consisting of prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411).

Disclosures: The study was supported by Eli Lilly and Company, USA. The lead author declared serving as a scientific advisor/clinical study investigator for various companies including Eli Lilly. Some of the authors are full-time employees or stakeholders of Eli Lilly, and a few others work for an alternative employer, which received compensation from Eli Lilly.

Source: Blauvelt A et al. Dermatol Ther (Heidelb). 2021 Oct 15. doi: 10.1007/s13555-021-00627-4.

Key clinical point: Compared with secukinumab, ixekizumab concorded with significantly increased adherence rates and decreased nonpersistence, discontinuation, and switching in biologic-experienced patients with psoriasis.

Major finding: After 18 months of follow-up, ixekizumab was associated with significantly higher rates of high treatment adherence (42% vs 35%; P = .019) and persistence (44.9% vs 36.9%; P = .007) and lower discontinuation (48.4% vs 56.0%; P = .018) and switching (26.6% vs 34.0%; P = .009) rates than secukinumab.

Study details: Findings are from a retrospective observational study consisting of prior biologic-experienced adult patients with psoriasis now receiving either secukinumab (n=780) or ixekizumab (n=411).

Disclosures: The study was supported by Eli Lilly and Company, USA. The lead author declared serving as a scientific advisor/clinical study investigator for various companies including Eli Lilly. Some of the authors are full-time employees or stakeholders of Eli Lilly, and a few others work for an alternative employer, which received compensation from Eli Lilly.

Source: Blauvelt A et al. Dermatol Ther (Heidelb). 2021 Oct 15. doi: 10.1007/s13555-021-00627-4.

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Tapinarof cream 1% QD efficacious against extensive plaque psoriasis in phase 2a

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Key clinical point: Tapinarof cream 1% applied once daily (QD) displayed significant efficacy after 4 weeks along with good tolerability and limited systemic exposure in patients with extensive plaque psoriasis.

Major finding: At day 29, the mean Psoriasis Area Severity Index score changed significantly with a mean percentage change from baseline of −59.56% (95% CI, −73.53% to −45.59%) and the tapinarof plasma concentration remained below the quantification level (< 50 pg/mL) in the majority (67.9%) of patients; 17 patients reported no irritation and 2 had mild irritation at the application site.

Study details: Findings are from a phase 2a trial involving 21 adult patients with extensive plaque psoriasis (20% or more body surface area involvement) who applied tapinarof cream 1% QD for 29 days.

Disclosures: The study was supported by Dermavant Sciences, Inc. Some of the authors, including the lead author, declared serving as an employee or investigator for Dermavant Sciences, Inc.

Source: Jett JE et al. Am J Clin Dermatol. 2021 Oct 28. doi: 10.1007/s40257-021-00641-4.

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Key clinical point: Tapinarof cream 1% applied once daily (QD) displayed significant efficacy after 4 weeks along with good tolerability and limited systemic exposure in patients with extensive plaque psoriasis.

Major finding: At day 29, the mean Psoriasis Area Severity Index score changed significantly with a mean percentage change from baseline of −59.56% (95% CI, −73.53% to −45.59%) and the tapinarof plasma concentration remained below the quantification level (< 50 pg/mL) in the majority (67.9%) of patients; 17 patients reported no irritation and 2 had mild irritation at the application site.

Study details: Findings are from a phase 2a trial involving 21 adult patients with extensive plaque psoriasis (20% or more body surface area involvement) who applied tapinarof cream 1% QD for 29 days.

Disclosures: The study was supported by Dermavant Sciences, Inc. Some of the authors, including the lead author, declared serving as an employee or investigator for Dermavant Sciences, Inc.

Source: Jett JE et al. Am J Clin Dermatol. 2021 Oct 28. doi: 10.1007/s40257-021-00641-4.

Key clinical point: Tapinarof cream 1% applied once daily (QD) displayed significant efficacy after 4 weeks along with good tolerability and limited systemic exposure in patients with extensive plaque psoriasis.

Major finding: At day 29, the mean Psoriasis Area Severity Index score changed significantly with a mean percentage change from baseline of −59.56% (95% CI, −73.53% to −45.59%) and the tapinarof plasma concentration remained below the quantification level (< 50 pg/mL) in the majority (67.9%) of patients; 17 patients reported no irritation and 2 had mild irritation at the application site.

Study details: Findings are from a phase 2a trial involving 21 adult patients with extensive plaque psoriasis (20% or more body surface area involvement) who applied tapinarof cream 1% QD for 29 days.

Disclosures: The study was supported by Dermavant Sciences, Inc. Some of the authors, including the lead author, declared serving as an employee or investigator for Dermavant Sciences, Inc.

Source: Jett JE et al. Am J Clin Dermatol. 2021 Oct 28. doi: 10.1007/s40257-021-00641-4.

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Is beta-blocker use in hypertension linked with psoriasis development?

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Key clinical point: Clinical avoidance of beta-blockers (BBs) should not be considered a prerequisite for solely avoiding the onset of de novo psoriasis in patients with hypertension.

Major finding: Overall, 0.2% and 0.4% of patients developed de novo psoriasis in the first and second years after BB initiation, which was not significantly different from patients without exposure to BB (P = .77 and P = .96; respectively). The odds of de novo psoriasis were not significantly higher in patients with exposure to BB than those unexposed (odds ratio, 1.00; 95% CI, 0.60-1.67).

Study details: Findings are from a nationwide population-based retrospective cohort study including 105,529 patients aged 19 years or above with hypertension who had not been diagnosed with psoriasis.

Disclosures: The authors did not report any source of funding. No conflict of interests was reported.

Source: Kim YE et al. J Eur Acad Dermatol Venereol. 2021 Oct 9. doi: 10.1111/jdv.17733.

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Key clinical point: Clinical avoidance of beta-blockers (BBs) should not be considered a prerequisite for solely avoiding the onset of de novo psoriasis in patients with hypertension.

Major finding: Overall, 0.2% and 0.4% of patients developed de novo psoriasis in the first and second years after BB initiation, which was not significantly different from patients without exposure to BB (P = .77 and P = .96; respectively). The odds of de novo psoriasis were not significantly higher in patients with exposure to BB than those unexposed (odds ratio, 1.00; 95% CI, 0.60-1.67).

Study details: Findings are from a nationwide population-based retrospective cohort study including 105,529 patients aged 19 years or above with hypertension who had not been diagnosed with psoriasis.

Disclosures: The authors did not report any source of funding. No conflict of interests was reported.

Source: Kim YE et al. J Eur Acad Dermatol Venereol. 2021 Oct 9. doi: 10.1111/jdv.17733.

Key clinical point: Clinical avoidance of beta-blockers (BBs) should not be considered a prerequisite for solely avoiding the onset of de novo psoriasis in patients with hypertension.

Major finding: Overall, 0.2% and 0.4% of patients developed de novo psoriasis in the first and second years after BB initiation, which was not significantly different from patients without exposure to BB (P = .77 and P = .96; respectively). The odds of de novo psoriasis were not significantly higher in patients with exposure to BB than those unexposed (odds ratio, 1.00; 95% CI, 0.60-1.67).

Study details: Findings are from a nationwide population-based retrospective cohort study including 105,529 patients aged 19 years or above with hypertension who had not been diagnosed with psoriasis.

Disclosures: The authors did not report any source of funding. No conflict of interests was reported.

Source: Kim YE et al. J Eur Acad Dermatol Venereol. 2021 Oct 9. doi: 10.1111/jdv.17733.

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Phase 2a supports infrequent bimekizumab dosing for plaque psoriasis maintenance

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Key clinical point: Bimekizumab may be dosed every 8 weeks during maintenance therapy for plaque psoriasis in contrast to the 4-week dosing regimen typically adopted for anti-interleukin-17A biologics.

Major finding: The absolute change in Psoriasis Area Severity Index (PASI) at week 28 in patients receiving an additional bimekizumab dose vs placebo was −19.7 (95% CI, −24.2 to −15.2) vs −10.8 (95% CI, −13.5 to −8.0). Patients receiving placebo vs bimekizumab at week 16 showed a higher reduction in PASI 100 (−34.4% vs −11.7%) and Investigator's Global Assessment 0/1 (−62.5% vs 0.0%) response rates between weeks 16 and 28.

Study details: This was a prospective phase 2a study including 49 patients with moderate-to-severe plaque psoriasis who received bimekizumab at weeks 0 and 4 and were subsequently randomly assigned to receive either placebo or bimekizumab third dose at week 16.

Disclosures: The study was sponsored by UCB Pharma. Most of the authors including the lead author declared serving as employees of UCB Pharma, and some received research grants or consultation fees from various sources including UCB Pharma.

Source: Oliver R et al. Br J Dermatol. 2021 Oct 23. doi: 10.1111/bjd.20827.

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Key clinical point: Bimekizumab may be dosed every 8 weeks during maintenance therapy for plaque psoriasis in contrast to the 4-week dosing regimen typically adopted for anti-interleukin-17A biologics.

Major finding: The absolute change in Psoriasis Area Severity Index (PASI) at week 28 in patients receiving an additional bimekizumab dose vs placebo was −19.7 (95% CI, −24.2 to −15.2) vs −10.8 (95% CI, −13.5 to −8.0). Patients receiving placebo vs bimekizumab at week 16 showed a higher reduction in PASI 100 (−34.4% vs −11.7%) and Investigator's Global Assessment 0/1 (−62.5% vs 0.0%) response rates between weeks 16 and 28.

Study details: This was a prospective phase 2a study including 49 patients with moderate-to-severe plaque psoriasis who received bimekizumab at weeks 0 and 4 and were subsequently randomly assigned to receive either placebo or bimekizumab third dose at week 16.

Disclosures: The study was sponsored by UCB Pharma. Most of the authors including the lead author declared serving as employees of UCB Pharma, and some received research grants or consultation fees from various sources including UCB Pharma.

Source: Oliver R et al. Br J Dermatol. 2021 Oct 23. doi: 10.1111/bjd.20827.

Key clinical point: Bimekizumab may be dosed every 8 weeks during maintenance therapy for plaque psoriasis in contrast to the 4-week dosing regimen typically adopted for anti-interleukin-17A biologics.

Major finding: The absolute change in Psoriasis Area Severity Index (PASI) at week 28 in patients receiving an additional bimekizumab dose vs placebo was −19.7 (95% CI, −24.2 to −15.2) vs −10.8 (95% CI, −13.5 to −8.0). Patients receiving placebo vs bimekizumab at week 16 showed a higher reduction in PASI 100 (−34.4% vs −11.7%) and Investigator's Global Assessment 0/1 (−62.5% vs 0.0%) response rates between weeks 16 and 28.

Study details: This was a prospective phase 2a study including 49 patients with moderate-to-severe plaque psoriasis who received bimekizumab at weeks 0 and 4 and were subsequently randomly assigned to receive either placebo or bimekizumab third dose at week 16.

Disclosures: The study was sponsored by UCB Pharma. Most of the authors including the lead author declared serving as employees of UCB Pharma, and some received research grants or consultation fees from various sources including UCB Pharma.

Source: Oliver R et al. Br J Dermatol. 2021 Oct 23. doi: 10.1111/bjd.20827.

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Novel CAL/BDP PAD-cream outshines the conventional counterpart

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Key clinical point: The novel calcipotriol (CAL)/betamethasone dipropionate (BDP) PAD-cream offered greater benefits than the currently available topical suspension/gel (CAL/BDP TS) in terms of efficacy and patient quality of life along with favorable safety in plaque psoriasis.

Major finding: At 8 weeks, CAL/BDP PAD-cream vs CAL/BDP TS was associated with a significantly higher Physician's Global Assessment success rate (43.2% vs 31.9%; P < .0001), mean percent reduction in modified Psoriasis Area Severity Index (64.6% vs 56.4%; P < .0001), and Dermatology Life Quality Index 0/1 response rate (43.8% vs 34.2%; P = .0005) and no adverse drug reaction with a frequency greater than 1%.

Study details: This is a pooled analysis of 2 phase 3 trials consisting of a combined 1,271 patients with mild-to-moderate plaque psoriasis, treated with either CAL/BDP PAD-cream (n=551), CAL/BDP TS (n=542), or vehicle (n=178).

Disclosures: Both trials were sponsored by MC2 Therapeutics, Denmark. Some of the authors including the lead author received investigator honoraria for phase 3 trials from MC2, and the rest are employees of MC2.

Source: Pinter A et al. J Eur Acad Dermatol Venereol. 2021 Oct 10. doi: 10.1111/jdv.17734.

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Key clinical point: The novel calcipotriol (CAL)/betamethasone dipropionate (BDP) PAD-cream offered greater benefits than the currently available topical suspension/gel (CAL/BDP TS) in terms of efficacy and patient quality of life along with favorable safety in plaque psoriasis.

Major finding: At 8 weeks, CAL/BDP PAD-cream vs CAL/BDP TS was associated with a significantly higher Physician's Global Assessment success rate (43.2% vs 31.9%; P < .0001), mean percent reduction in modified Psoriasis Area Severity Index (64.6% vs 56.4%; P < .0001), and Dermatology Life Quality Index 0/1 response rate (43.8% vs 34.2%; P = .0005) and no adverse drug reaction with a frequency greater than 1%.

Study details: This is a pooled analysis of 2 phase 3 trials consisting of a combined 1,271 patients with mild-to-moderate plaque psoriasis, treated with either CAL/BDP PAD-cream (n=551), CAL/BDP TS (n=542), or vehicle (n=178).

Disclosures: Both trials were sponsored by MC2 Therapeutics, Denmark. Some of the authors including the lead author received investigator honoraria for phase 3 trials from MC2, and the rest are employees of MC2.

Source: Pinter A et al. J Eur Acad Dermatol Venereol. 2021 Oct 10. doi: 10.1111/jdv.17734.

Key clinical point: The novel calcipotriol (CAL)/betamethasone dipropionate (BDP) PAD-cream offered greater benefits than the currently available topical suspension/gel (CAL/BDP TS) in terms of efficacy and patient quality of life along with favorable safety in plaque psoriasis.

Major finding: At 8 weeks, CAL/BDP PAD-cream vs CAL/BDP TS was associated with a significantly higher Physician's Global Assessment success rate (43.2% vs 31.9%; P < .0001), mean percent reduction in modified Psoriasis Area Severity Index (64.6% vs 56.4%; P < .0001), and Dermatology Life Quality Index 0/1 response rate (43.8% vs 34.2%; P = .0005) and no adverse drug reaction with a frequency greater than 1%.

Study details: This is a pooled analysis of 2 phase 3 trials consisting of a combined 1,271 patients with mild-to-moderate plaque psoriasis, treated with either CAL/BDP PAD-cream (n=551), CAL/BDP TS (n=542), or vehicle (n=178).

Disclosures: Both trials were sponsored by MC2 Therapeutics, Denmark. Some of the authors including the lead author received investigator honoraria for phase 3 trials from MC2, and the rest are employees of MC2.

Source: Pinter A et al. J Eur Acad Dermatol Venereol. 2021 Oct 10. doi: 10.1111/jdv.17734.

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Preventing psoriasis relapse after ustekinumab withdrawal using abatacept: A failed attempt

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Key clinical point: Abatacept-mediated CD28-CD80/CD86 blockade was inept at averting psoriasis relapse following ustekinumab withdrawal in patients with moderate-to-severe plaque psoriasis.

Major finding: Between weeks 12 and 88, abatacept vs ustekinumab groups displayed similar relapse rates (91.1% vs 87.0%; P = .41) and median time to relapse from the last dose of ustekinumab (36 weeks [95% CI, 36-48] vs 32 weeks [95% CI, 28-40]).

Study details: The data come from the PAUSE trial, including 91 adult patients with moderate-to-severe plaque psoriasis who achieved Psoriasis Area Severity Index 75 at week 12 of receiving ustekinumab and who were randomly assigned to either continued ustekinumab or switch to abatacept until week 39.

Disclosures: The study was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and Eli Lilly and Co. Some of the authors declared receiving research/institutional grants and/or personal fees from various sources, including Eli Lilly.

Source: Harris KM et al. JAMA Dermatol. 2021 Oct 13. doi: 10.1001/jamadermatol.2021.3492.

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Key clinical point: Abatacept-mediated CD28-CD80/CD86 blockade was inept at averting psoriasis relapse following ustekinumab withdrawal in patients with moderate-to-severe plaque psoriasis.

Major finding: Between weeks 12 and 88, abatacept vs ustekinumab groups displayed similar relapse rates (91.1% vs 87.0%; P = .41) and median time to relapse from the last dose of ustekinumab (36 weeks [95% CI, 36-48] vs 32 weeks [95% CI, 28-40]).

Study details: The data come from the PAUSE trial, including 91 adult patients with moderate-to-severe plaque psoriasis who achieved Psoriasis Area Severity Index 75 at week 12 of receiving ustekinumab and who were randomly assigned to either continued ustekinumab or switch to abatacept until week 39.

Disclosures: The study was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and Eli Lilly and Co. Some of the authors declared receiving research/institutional grants and/or personal fees from various sources, including Eli Lilly.

Source: Harris KM et al. JAMA Dermatol. 2021 Oct 13. doi: 10.1001/jamadermatol.2021.3492.

Key clinical point: Abatacept-mediated CD28-CD80/CD86 blockade was inept at averting psoriasis relapse following ustekinumab withdrawal in patients with moderate-to-severe plaque psoriasis.

Major finding: Between weeks 12 and 88, abatacept vs ustekinumab groups displayed similar relapse rates (91.1% vs 87.0%; P = .41) and median time to relapse from the last dose of ustekinumab (36 weeks [95% CI, 36-48] vs 32 weeks [95% CI, 28-40]).

Study details: The data come from the PAUSE trial, including 91 adult patients with moderate-to-severe plaque psoriasis who achieved Psoriasis Area Severity Index 75 at week 12 of receiving ustekinumab and who were randomly assigned to either continued ustekinumab or switch to abatacept until week 39.

Disclosures: The study was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and Eli Lilly and Co. Some of the authors declared receiving research/institutional grants and/or personal fees from various sources, including Eli Lilly.

Source: Harris KM et al. JAMA Dermatol. 2021 Oct 13. doi: 10.1001/jamadermatol.2021.3492.

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Does the use of frankincense make sense in dermatology?

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The Boswellia serrata exudate or gum (known in India as “guggulu”) that forms an aromatic resin traditionally used as incense – and known as frankincense (especially when retrieved from Boswellia species found in Eritrea and Somalia but also from the Indian variety) – has been considered for thousands of years to possess therapeutic properties. It is used in Ayurvedic medicine, as well as in traditional medicine in China and the Middle East, particularly for its anti-inflammatory effects to treat chronic conditions.1-8 In fact, such essential oils have been used since 2800 BC to treat various inflammatory conditions, including skin sores and wounds, as well as in perfumes and incense.2,9 In the West, use of frankincense dates back to thousands of years as well, more often found in the form of incense for religious and cultural ceremonies.7 Over the past 2 decades, evidence supporting the use of frankincense for therapeutic medical purposes has increased, particularly because of its purported anti-inflammatory and anticancer properties.3 This column focuses on some of the emerging data on this ancient botanical agent.

Madeleine_Steinbach / iStock / Getty Images Plus

Chemical constituents

Terpenoids and essential oils are the primary components of frankincense and are known to impart anti-inflammatory and anticancer activity. The same is true for myrrh, which has been combined with frankincense in traditional Chinese medicine as a single medication for millennia, with the two acting synergistically and considered still to be a potent combination in conferring various biological benefits.7

In 2010, in a systematic review of the anti-inflammatory and anticancer activities of Boswellia species and their chemical ingredients, Efferth and Oesch found that frankincense blocks the production of leukotrienes, cyclooxygenase (COX) 1 and 2, as well as 5-lipoxygenase; and oxidative stress. It also contributes to regulation of immune cells from the innate and acquired immune systems and exerts anticancer activity by influencing signaling transduction responsible for cell cycle arrest, as well as inhibition of proliferation, angiogenesis, invasion, and metastasis. The investigators also reported on clinical trial results that have found efficacy of frankincense and its constituents in ameliorating symptoms of psoriasis and erythematous eczema, among other disorders.3

Dr. Leslie S. Baumann

Anti-inflammatory activity

Li et al. completed a study in 2016 to identify the active ingredients responsible for the anti-inflammatory and analgesic effects of frankincense. They found that alpha-pinene, linalool, and 1-octanol were key contributors. These constituents were noted for suppressing COX-2 overexpression in mice, as well as nociceptive stimulus-induced inflammatory infiltrates.10

Noting the increasing popularity of frankincense essential oil in skin care, despite a paucity of data, in 2017, Han et al. evaluated the biological activities of the essential oil in pre-inflamed human dermal fibroblasts using 17 key protein biomarkers. Frankincense essential oil displayed significant antiproliferative activity and suppressed collagen III, interferon gamma-induced protein 10, and intracellular adhesion molecule 1. The investigators referred to the overall encouraging potential of frankincense essential oil to exert influence over inflammation and tissue remodeling in human skin and called for additional research into its mechanisms of action and active constituents.11

 

 

Anticancer activity

The main active ingredient in frankincense, boswellic acid, has been shown to promote apoptosis, suppress matrix metalloproteinase secretion, and hinder migration in metastatic melanoma cell lines in mice.6,12

In 2019, Hakkim et al. demonstrated that frankincense essential oil yielded substantial antimelanoma activity in vitro and in vivo and ameliorated hepatotoxicity caused by acetaminophen.13

There is one case report in the literature on the use of frankincense as a treatment for skin cancer. A 56-year-old man received frankincense oil multiple times a day for 4 months to treat a nodular basal cell carcinoma on one arm (which resolved) and an infiltrative BCC on the chest (some focal residual tumor remained).6,14 Topical frankincense or boswellic acid has been given a grade D recommendation for treating skin cancer, however, because of only one level-of-evidence-5 study.6

Antimicrobial activity

In 2012, de Rapper et al. collected samples of three essential oils of frankincense (Boswellia rivae, Boswellia neglecta, and Boswellia papyrifera) and two essential oil samples of myrrh and sweet myrrh from different regions of Ethiopia to study their anti-infective properties alone and in combination. The investigators observed synergistic and additive effects, particularly between B. papyrifera and Commiphora myrrha. While noting the long history of the combined use of frankincense and myrrh essential oils since 1500 BC, the investigators highlighted their study as the first antimicrobial work to verify the effectiveness of this combination, validating the use of this combination to thwart particular pathogens.15

Just 2 years ago, Ljaljević Grbić et al. evaluated the in vitro antimicrobial potential of the liquid and vapor phases of B. carteri and C. myrrha (frankincense and myrrh, respectively) essential oils, finding that frankincense demonstrated marked capacity to act as a natural antimicrobial agent.9

Transdermal delivery

In 2017, Zhu et al. showed that frankincense and myrrh essential oils promoted the permeability of the Chinese herb Chuanxiong and may facilitate drug elimination from the epidermis via dermal capillaries by dint of improved cutaneous blood flow, thereby augmenting transdermal drug delivery.16 The same team also showed that frankincense and myrrh essential oils, by fostering permeation by enhancing drug delivery across the stratum corneum, can also alter the structure of the stratum corneum.17

Conclusion

The use of frankincense in traditional medicine has a long and impressive track record. Recent research provides reason for optimism, and further investigating the possible incorporation of this botanical agent into modern dermatologic therapies appears warranted. Clearly, however, much more research is needed.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Kimmatkar N et al. Phytomedicine. 2003 Jan;10(1):3-7.

2. Ammon HP. Wien Med Wochenschr. 2002;152(15-16):373-8.

3. Efferth T & Oesch F. Semin Cancer Biol. 2020 Feb 4;S1044-579X(20)30034-1.

4. Banno N et al. J Ethnopharmacol. 2006 Sep 19;107(2):249-53.

5. Poeckel D & Werz O. Curr Med Chem. 2006;13(28):3359-69.

6. Li JY, Kampp JT. Dermatol Surg. 2019 Jan;45(1):58-67.

7. Cao B et al. Molecules. 2019 Aug 24;24(17): 3076.

8. Mertens M et al. Flavour Fragr J. 2009;24:279-300.

9. Ljaljević Grbić M et al. J Ethnopharmacol. 2018 Jun 12;219:1-14.

10. Li XJ et al. J Ethnopharmacol. 2016 Feb 17;179:22-6.

11. Han X et al. Biochim Open. 2017 Feb 3;4:31-5.

12. Zhao W et al. Cancer Detect Prev. 2003;27:67-75.

13. Hakkim FL et al. Oncotarget. 2019 May 28;10(37):3472-90.

14. Fung K et al. OA Altern Med 2013;1:14.

15. de Rapper S et al. Lett Appl Microbiol. 2012 Apr;54(4):352-8.

16. Zhu XF et al. Zhongguo Zhong Yao Za Zhi. 2017 Feb;42(4):680-5.

17. Guan YM et al. Zhongguo Zhong Yao Za Zhi. 2017 Sep;42(17):3350-5.

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The Boswellia serrata exudate or gum (known in India as “guggulu”) that forms an aromatic resin traditionally used as incense – and known as frankincense (especially when retrieved from Boswellia species found in Eritrea and Somalia but also from the Indian variety) – has been considered for thousands of years to possess therapeutic properties. It is used in Ayurvedic medicine, as well as in traditional medicine in China and the Middle East, particularly for its anti-inflammatory effects to treat chronic conditions.1-8 In fact, such essential oils have been used since 2800 BC to treat various inflammatory conditions, including skin sores and wounds, as well as in perfumes and incense.2,9 In the West, use of frankincense dates back to thousands of years as well, more often found in the form of incense for religious and cultural ceremonies.7 Over the past 2 decades, evidence supporting the use of frankincense for therapeutic medical purposes has increased, particularly because of its purported anti-inflammatory and anticancer properties.3 This column focuses on some of the emerging data on this ancient botanical agent.

Madeleine_Steinbach / iStock / Getty Images Plus

Chemical constituents

Terpenoids and essential oils are the primary components of frankincense and are known to impart anti-inflammatory and anticancer activity. The same is true for myrrh, which has been combined with frankincense in traditional Chinese medicine as a single medication for millennia, with the two acting synergistically and considered still to be a potent combination in conferring various biological benefits.7

In 2010, in a systematic review of the anti-inflammatory and anticancer activities of Boswellia species and their chemical ingredients, Efferth and Oesch found that frankincense blocks the production of leukotrienes, cyclooxygenase (COX) 1 and 2, as well as 5-lipoxygenase; and oxidative stress. It also contributes to regulation of immune cells from the innate and acquired immune systems and exerts anticancer activity by influencing signaling transduction responsible for cell cycle arrest, as well as inhibition of proliferation, angiogenesis, invasion, and metastasis. The investigators also reported on clinical trial results that have found efficacy of frankincense and its constituents in ameliorating symptoms of psoriasis and erythematous eczema, among other disorders.3

Dr. Leslie S. Baumann

Anti-inflammatory activity

Li et al. completed a study in 2016 to identify the active ingredients responsible for the anti-inflammatory and analgesic effects of frankincense. They found that alpha-pinene, linalool, and 1-octanol were key contributors. These constituents were noted for suppressing COX-2 overexpression in mice, as well as nociceptive stimulus-induced inflammatory infiltrates.10

Noting the increasing popularity of frankincense essential oil in skin care, despite a paucity of data, in 2017, Han et al. evaluated the biological activities of the essential oil in pre-inflamed human dermal fibroblasts using 17 key protein biomarkers. Frankincense essential oil displayed significant antiproliferative activity and suppressed collagen III, interferon gamma-induced protein 10, and intracellular adhesion molecule 1. The investigators referred to the overall encouraging potential of frankincense essential oil to exert influence over inflammation and tissue remodeling in human skin and called for additional research into its mechanisms of action and active constituents.11

 

 

Anticancer activity

The main active ingredient in frankincense, boswellic acid, has been shown to promote apoptosis, suppress matrix metalloproteinase secretion, and hinder migration in metastatic melanoma cell lines in mice.6,12

In 2019, Hakkim et al. demonstrated that frankincense essential oil yielded substantial antimelanoma activity in vitro and in vivo and ameliorated hepatotoxicity caused by acetaminophen.13

There is one case report in the literature on the use of frankincense as a treatment for skin cancer. A 56-year-old man received frankincense oil multiple times a day for 4 months to treat a nodular basal cell carcinoma on one arm (which resolved) and an infiltrative BCC on the chest (some focal residual tumor remained).6,14 Topical frankincense or boswellic acid has been given a grade D recommendation for treating skin cancer, however, because of only one level-of-evidence-5 study.6

Antimicrobial activity

In 2012, de Rapper et al. collected samples of three essential oils of frankincense (Boswellia rivae, Boswellia neglecta, and Boswellia papyrifera) and two essential oil samples of myrrh and sweet myrrh from different regions of Ethiopia to study their anti-infective properties alone and in combination. The investigators observed synergistic and additive effects, particularly between B. papyrifera and Commiphora myrrha. While noting the long history of the combined use of frankincense and myrrh essential oils since 1500 BC, the investigators highlighted their study as the first antimicrobial work to verify the effectiveness of this combination, validating the use of this combination to thwart particular pathogens.15

Just 2 years ago, Ljaljević Grbić et al. evaluated the in vitro antimicrobial potential of the liquid and vapor phases of B. carteri and C. myrrha (frankincense and myrrh, respectively) essential oils, finding that frankincense demonstrated marked capacity to act as a natural antimicrobial agent.9

Transdermal delivery

In 2017, Zhu et al. showed that frankincense and myrrh essential oils promoted the permeability of the Chinese herb Chuanxiong and may facilitate drug elimination from the epidermis via dermal capillaries by dint of improved cutaneous blood flow, thereby augmenting transdermal drug delivery.16 The same team also showed that frankincense and myrrh essential oils, by fostering permeation by enhancing drug delivery across the stratum corneum, can also alter the structure of the stratum corneum.17

Conclusion

The use of frankincense in traditional medicine has a long and impressive track record. Recent research provides reason for optimism, and further investigating the possible incorporation of this botanical agent into modern dermatologic therapies appears warranted. Clearly, however, much more research is needed.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Kimmatkar N et al. Phytomedicine. 2003 Jan;10(1):3-7.

2. Ammon HP. Wien Med Wochenschr. 2002;152(15-16):373-8.

3. Efferth T & Oesch F. Semin Cancer Biol. 2020 Feb 4;S1044-579X(20)30034-1.

4. Banno N et al. J Ethnopharmacol. 2006 Sep 19;107(2):249-53.

5. Poeckel D & Werz O. Curr Med Chem. 2006;13(28):3359-69.

6. Li JY, Kampp JT. Dermatol Surg. 2019 Jan;45(1):58-67.

7. Cao B et al. Molecules. 2019 Aug 24;24(17): 3076.

8. Mertens M et al. Flavour Fragr J. 2009;24:279-300.

9. Ljaljević Grbić M et al. J Ethnopharmacol. 2018 Jun 12;219:1-14.

10. Li XJ et al. J Ethnopharmacol. 2016 Feb 17;179:22-6.

11. Han X et al. Biochim Open. 2017 Feb 3;4:31-5.

12. Zhao W et al. Cancer Detect Prev. 2003;27:67-75.

13. Hakkim FL et al. Oncotarget. 2019 May 28;10(37):3472-90.

14. Fung K et al. OA Altern Med 2013;1:14.

15. de Rapper S et al. Lett Appl Microbiol. 2012 Apr;54(4):352-8.

16. Zhu XF et al. Zhongguo Zhong Yao Za Zhi. 2017 Feb;42(4):680-5.

17. Guan YM et al. Zhongguo Zhong Yao Za Zhi. 2017 Sep;42(17):3350-5.

The Boswellia serrata exudate or gum (known in India as “guggulu”) that forms an aromatic resin traditionally used as incense – and known as frankincense (especially when retrieved from Boswellia species found in Eritrea and Somalia but also from the Indian variety) – has been considered for thousands of years to possess therapeutic properties. It is used in Ayurvedic medicine, as well as in traditional medicine in China and the Middle East, particularly for its anti-inflammatory effects to treat chronic conditions.1-8 In fact, such essential oils have been used since 2800 BC to treat various inflammatory conditions, including skin sores and wounds, as well as in perfumes and incense.2,9 In the West, use of frankincense dates back to thousands of years as well, more often found in the form of incense for religious and cultural ceremonies.7 Over the past 2 decades, evidence supporting the use of frankincense for therapeutic medical purposes has increased, particularly because of its purported anti-inflammatory and anticancer properties.3 This column focuses on some of the emerging data on this ancient botanical agent.

Madeleine_Steinbach / iStock / Getty Images Plus

Chemical constituents

Terpenoids and essential oils are the primary components of frankincense and are known to impart anti-inflammatory and anticancer activity. The same is true for myrrh, which has been combined with frankincense in traditional Chinese medicine as a single medication for millennia, with the two acting synergistically and considered still to be a potent combination in conferring various biological benefits.7

In 2010, in a systematic review of the anti-inflammatory and anticancer activities of Boswellia species and their chemical ingredients, Efferth and Oesch found that frankincense blocks the production of leukotrienes, cyclooxygenase (COX) 1 and 2, as well as 5-lipoxygenase; and oxidative stress. It also contributes to regulation of immune cells from the innate and acquired immune systems and exerts anticancer activity by influencing signaling transduction responsible for cell cycle arrest, as well as inhibition of proliferation, angiogenesis, invasion, and metastasis. The investigators also reported on clinical trial results that have found efficacy of frankincense and its constituents in ameliorating symptoms of psoriasis and erythematous eczema, among other disorders.3

Dr. Leslie S. Baumann

Anti-inflammatory activity

Li et al. completed a study in 2016 to identify the active ingredients responsible for the anti-inflammatory and analgesic effects of frankincense. They found that alpha-pinene, linalool, and 1-octanol were key contributors. These constituents were noted for suppressing COX-2 overexpression in mice, as well as nociceptive stimulus-induced inflammatory infiltrates.10

Noting the increasing popularity of frankincense essential oil in skin care, despite a paucity of data, in 2017, Han et al. evaluated the biological activities of the essential oil in pre-inflamed human dermal fibroblasts using 17 key protein biomarkers. Frankincense essential oil displayed significant antiproliferative activity and suppressed collagen III, interferon gamma-induced protein 10, and intracellular adhesion molecule 1. The investigators referred to the overall encouraging potential of frankincense essential oil to exert influence over inflammation and tissue remodeling in human skin and called for additional research into its mechanisms of action and active constituents.11

 

 

Anticancer activity

The main active ingredient in frankincense, boswellic acid, has been shown to promote apoptosis, suppress matrix metalloproteinase secretion, and hinder migration in metastatic melanoma cell lines in mice.6,12

In 2019, Hakkim et al. demonstrated that frankincense essential oil yielded substantial antimelanoma activity in vitro and in vivo and ameliorated hepatotoxicity caused by acetaminophen.13

There is one case report in the literature on the use of frankincense as a treatment for skin cancer. A 56-year-old man received frankincense oil multiple times a day for 4 months to treat a nodular basal cell carcinoma on one arm (which resolved) and an infiltrative BCC on the chest (some focal residual tumor remained).6,14 Topical frankincense or boswellic acid has been given a grade D recommendation for treating skin cancer, however, because of only one level-of-evidence-5 study.6

Antimicrobial activity

In 2012, de Rapper et al. collected samples of three essential oils of frankincense (Boswellia rivae, Boswellia neglecta, and Boswellia papyrifera) and two essential oil samples of myrrh and sweet myrrh from different regions of Ethiopia to study their anti-infective properties alone and in combination. The investigators observed synergistic and additive effects, particularly between B. papyrifera and Commiphora myrrha. While noting the long history of the combined use of frankincense and myrrh essential oils since 1500 BC, the investigators highlighted their study as the first antimicrobial work to verify the effectiveness of this combination, validating the use of this combination to thwart particular pathogens.15

Just 2 years ago, Ljaljević Grbić et al. evaluated the in vitro antimicrobial potential of the liquid and vapor phases of B. carteri and C. myrrha (frankincense and myrrh, respectively) essential oils, finding that frankincense demonstrated marked capacity to act as a natural antimicrobial agent.9

Transdermal delivery

In 2017, Zhu et al. showed that frankincense and myrrh essential oils promoted the permeability of the Chinese herb Chuanxiong and may facilitate drug elimination from the epidermis via dermal capillaries by dint of improved cutaneous blood flow, thereby augmenting transdermal drug delivery.16 The same team also showed that frankincense and myrrh essential oils, by fostering permeation by enhancing drug delivery across the stratum corneum, can also alter the structure of the stratum corneum.17

Conclusion

The use of frankincense in traditional medicine has a long and impressive track record. Recent research provides reason for optimism, and further investigating the possible incorporation of this botanical agent into modern dermatologic therapies appears warranted. Clearly, however, much more research is needed.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Kimmatkar N et al. Phytomedicine. 2003 Jan;10(1):3-7.

2. Ammon HP. Wien Med Wochenschr. 2002;152(15-16):373-8.

3. Efferth T & Oesch F. Semin Cancer Biol. 2020 Feb 4;S1044-579X(20)30034-1.

4. Banno N et al. J Ethnopharmacol. 2006 Sep 19;107(2):249-53.

5. Poeckel D & Werz O. Curr Med Chem. 2006;13(28):3359-69.

6. Li JY, Kampp JT. Dermatol Surg. 2019 Jan;45(1):58-67.

7. Cao B et al. Molecules. 2019 Aug 24;24(17): 3076.

8. Mertens M et al. Flavour Fragr J. 2009;24:279-300.

9. Ljaljević Grbić M et al. J Ethnopharmacol. 2018 Jun 12;219:1-14.

10. Li XJ et al. J Ethnopharmacol. 2016 Feb 17;179:22-6.

11. Han X et al. Biochim Open. 2017 Feb 3;4:31-5.

12. Zhao W et al. Cancer Detect Prev. 2003;27:67-75.

13. Hakkim FL et al. Oncotarget. 2019 May 28;10(37):3472-90.

14. Fung K et al. OA Altern Med 2013;1:14.

15. de Rapper S et al. Lett Appl Microbiol. 2012 Apr;54(4):352-8.

16. Zhu XF et al. Zhongguo Zhong Yao Za Zhi. 2017 Feb;42(4):680-5.

17. Guan YM et al. Zhongguo Zhong Yao Za Zhi. 2017 Sep;42(17):3350-5.

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Management of Pediatric Nail Psoriasis

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Sun, 11/07/2021 - 15:24
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Management of Pediatric Nail Psoriasis

Pediatric nail psoriasis is a condition that has not been extensively studied. The prevalence of nail alterations in pediatric patients with psoriasis varies among different studies, ranging from 17% to 39.2%.1 Nail pitting, onycholysis associated with subungual hyperkeratosis, paronychia, and pachyonychia are the most frequent features of psoriatic nail involvement in children.2,3 The management of nail psoriasis in children and adolescents is critical due to the quality-of-life impact, from potential functional impairment issues to the obvious cosmetic problems, which can aggravate the psychologic distress and social embarrassment of patients with psoriasis. Despite the emergence of modern potent systemic agents to treat chronic plaque psoriasis, nail psoriasis often is refractory to treatment.4 Coupled with the limited on-label options for psoriasis treatment in children, the management of nail psoriasis in this special patient group constitutes an even greater therapeutic challenge. This report aims to summarize the limited existing data on the successful management of nail psoriasis in the pediatric population.

Reviewing the Literature on Nail Psoriasis

We conducted a search of PubMed articles indexed for MEDLINE, Embase, and Scopus using the following Medical Subject Headings key terms: nail psoriasis and children, juvenile, pediatric. Additional articles were identified from the reference lists of the retrieved articles and citations. Our search included reports in the English language published from 2000 to 2019. The selection process included the following 2 steps: screening of the titles and abstracts, followed by evaluation of the selected full-text articles.

Topical Treatments for Nail Psoriasis

Because most systemic antipsoriatic treatments that can be administered in adult patients have not yet been granted an official license for administration in children, topical treatments are considered by many physicians as the preferred first-line therapy for psoriatic nail involvement in pediatric patients.5,6 However, only scarce data are available in the literature concerning the successful use of local agents in pediatric patients with psoriasis.

The main limitation of local treatments relates mostly to their impaired penetration into the affected area (nails). To optimize drug penetration, some authors suggest the use of potent keratolytic topical preparations to reduce the nail volume and facilitate drug absorption.7 A popular suggestion is trimming the onycholytic nail plate followed by 40% urea avulsion to treat subungual hyperkeratosis8 or simply the use of occlusive 40% urea in petroleum jelly.9 Other approaches include clipping the onycholytic nail over the diseased nail bed or processing the nail plate through grinding or even drilling holes with the use of mechanical burrs or ablative lasers to enhance the penetration of the topical agent.7

A frequent approach in pediatric patients is clipping the detached nails combined with daily application of calcipotriene (calcipotriol) and steroids, such as betamethasone dipropionate.5,8 Reports on the use of regimens with clobetasol propionate ointment 0.05% under occlusion, with or without the concomitant use of calcipotriol solution 0.005%, also are present in the literature but not always with satisfactory results.10,11 Another successfully administered topical steroid is mometasone furoate cream 0.1%.12 Although the use of intralesional triamcinolone acetonide also has demonstrated encouraging outcomes in isolated reports,13 associated adverse events, such as pain and hematomas, can result in tolerability issues for pediatric patients.7

Piraccini et al14 described the case of an 8-year-old patient with pustular nail psoriasis who showed improvement within 3 to 6 months of treatment with topical calcipotriol 5 μg/g as monotherapy applied to the nail and periungual tissues twice daily. Another approach, described by Diluvio et al,15 is the use of tazarotene gel 0.05% applied once daily to the affected nail plates, nail folds, and periungual skin without occlusion. In a 6-year-old patient with isolated nail psoriasis, this treatment regimen demonstrated notable improvement within 8 weeks.15

Systemic Treatments for Nail Psoriasis

Data on the successful administration of systemic agents in pediatric patients also are extremely scarce. Due to the lack of clinical trials, everyday practice is mostly based on isolated case series and case reports.

 

 

Methotrexate—Lee11 described the case of an 11-year-old girl with severe, symptomatic, 20-nail psoriatic onychodystrophy who showed a complete response to oral methotrexate 5 mg/wk after topical clobetasol propionate and calcipotriol failed. Improvement was seen as early as 4 weeks after therapy initiation, and complete resolution of the lesions was documented after 9 and 13 months of methotrexate therapy for the fingers and toes, respectively.11 The successful use of methotrexate in the improvement of psoriatic nail dystrophy in a pediatric patient also was documented by Teran et al.16 In this case, a 9-year-old girl with erythrodermic psoriasis, psoriatic arthritis, and severe onychodystrophy showed notable amelioration of all psoriatic manifestations, including the nail findings, with systemic methotrexate therapy (dose not specified).16 Notably, the authors reported that the improvement of onychodystrophy occurred with considerable delay compared to the other psoriatic lesions,16 indicating the already-known refractoriness of nail psoriasis to the various therapeutic attempts.9-15

Acitretin—Another agent that has been linked with partial improvement of acrodermatitis continua of Hallopeau (ACH)–associated onychodystrophy is acitretin. In a case series of 15 pediatric patients with pustular psoriasis, a 5-year-old boy with severe nail involvement presented with partial amelioration of nail changes with acitretin within the first 6 weeks of treatment using the following regimen: initial dosage of 0.8 mg/kg/d for 6 weeks, followed by 0.3 mg/kg/d for 4 weeks.17

Biologics—The emerging use of biologics in pediatric psoriasis also has brought important advances in the successful management of nail psoriasis in children and adolescents.18-21 Wells et al18 presented the case of an 8-year-old girl with nail psoriasis, psoriatic arthritis, and plaque psoriasis who showed complete resolution of all psoriatic manifestations, including nail involvement, within 3 months of treatment with secukinumab 150 mg subcutaneously every 4 weeks. Prior failed treatments included various systemic agents (ie, subcutaneous methotrexate 20 mg/m2, etanercept 0.8 mg/kg weekly, adalimumab 40 mg every 2 weeks) as well as topical agents (ie, urea, tazarotene, corticosteroids) and intralesional triamcinolone.18

Infliximab also has been successfully used for pediatric nail psoriasis. Watabe et al19 presented the case of an 8-year-old girl with psoriatic onychodystrophy in addition to psoriatic onycho-pachydermo-periostitis. Prior therapy with adalimumab 20 mg every other week combined with methotrexate 10 mg weekly failed. She experienced notable amelioration of the nail dystrophy within 3 months of using a combination of infliximab and methotrexate (infliximab 5 mg/kg intravenously on weeks 0, 2, and 6, and every 8 weeks thereafter; methotrexate 10 mg/wk).19

Cases in which infliximab has resulted in rapid yet only transient restoration of psoriatic onychodystrophy also are present in the literature. Pereira et al20 reported that a 3-year-old patient with severe 20-digit onychodystrophy in addition to pustular psoriasis had complete resolution of nail lesions within 2 weeks of treatment with infliximab (5 mg/kg at weeks 0, 2, and 6, and then every 7 weeks thereafter), which was sustained over the course of 1 year. The therapy had to be discontinued because of exacerbation of the cutaneous symptoms; thereafter, etanercept was initiated. Although the patient noted major improvement of all skin lesions under etanercept, only moderate amelioration of the psoriatic nail lesions was demonstrated.20

 

 

Dini et al21 described a 9-year-old girl with severe ACH-associated psoriatic onychodystrophy who showed complete clearance of all lesions within 8 weeks of treatment with adalimumab (initially 80 mg, followed by 40 mg after 1 week and then 40 mg every other week). Prior treatment with potent topical corticosteroids, cyclosporine (3 mg/kg/d for 6 months), and etanercept (0.4 mg/kg twice weekly for 3 months) was ineffective.21

Phototherapy—Other systemic agents with reported satisfactory outcomes in the treatment of psoriatic onychodystrophy include thalidomide combined with UVB phototherapy. Kiszewski et al22 described a 2-year-old patient with ACH and severe 19-digit onychodystrophy. Prior failed therapies included occluded clobetasol ointment 0.05%, occluded pimecrolimus 0.1%, and systemic methotrexate, while systemic acitretin (0.8 mg⁄kg⁄d) resulted in elevated cholesterol levels and therefore had to be interrupted. Improvement was seen 2 months after the initiation of a combined broadband UVB and thalidomide (50 mg⁄d) treatment, with no documented relapses after discontinuation of therapy.22

Narrowband UVB (311 nm) also has been used as monotherapy for ACH-associated onychodystrophy, as demonstrated by Bordignon et al.23 They reported a 9-year-old patient who showed partial improvement of isolated onychodystrophy of the fourth nail plate of the left hand after 36 sessions of narrowband UVB using a 311-nm filtering handpiece with a square spot size of 19×19 mm.23

Conclusion

Nail psoriasis constitutes a type of psoriasis that is not only refractory to most treatments but is accompanied by substantial psychological and occasionally functional burden for the affected individuals.24 Data concerning therapeutic options in the pediatric population are extremely limited, and therefore the everyday practice often involves administration of off-label medications, which can constitute a dilemma for many physicians, especially for safety.10 We suggest a simple therapeutic algorithm for the management of pediatric nail psoriasis based on the summarized data that are currently available in the literature. This algorithm is shown in the eFigure.

eFIGURE. Proposed algorithm for the management of nail psoriasis in children.

As progressively more agents—especially biologics—receive approval for use in plaque psoriasis in pediatric patients,25 it is expected that gradually more real-life data on their side efficacy for plaque psoriasis of the nails in children also will come to light. Furthermore, their on-label use in pediatric psoriasis patients will facilitate further relevant clinical trials to this target group so that the potential of these medications in the management of nail psoriasis can be fully explored.

References
  1. Uber M, Carvalho VO, Abagge KT, et al. Clinical features and nail clippings in 52 children with psoriasis. Pediatr Dermatol. 2018;35:202-207.
  2. Pourchot D, Bodemer C, Phan A, et al. Nail psoriasis: a systematic evaluation in 313 children with psoriasis. Pediatr Dermatol. 2017;34:58-63.
  3. Piraccini BM, Triantafyllopoulou I, Prevezas C, et al. Nail psoriasis in children: common or uncommon? results from a 10-year double-center study. Skin Appendage Disord. 2015;1:43-48.
  4. Baran R. The burden of nail psoriasis: an introduction. Dermatology. 2010;221(suppl 1):1-5.
  5. Richert B, André J. Nail disorders in children: diagnosis and management. Am J Clin Dermatol. 2011;12:101-112.
  6. Trüeb RM. Therapies for childhood psoriasis. Curr Probl Dermatol. 2009;38:137-159.
  7. Haneke E. Nail psoriasis: clinical features, pathogenesis, differential diagnoses, and management. Psoriasis (Auckl). 2017;7:51-63.
  8. Piraccini BM, Starace M. Nail disorders in infants and children. Curr Opin Pediatr. 2014;26:440-445.
  9. Duran-McKinster C, Ortiz-Solis D, Granados J, et al. Juvenile psoriatic arthritis with nail psoriasis in the absence of cutaneous lesions. Int J Dermatol. 2000;39:32-35.
  10. Holzberg M, Ruben BS, Baran R. Psoriasis restricted to the nail in a 7-year-old child. should biologics be an appropriate treatment modality when considering quality of life? J Eur Acad Dermatol Venereol. 2014;28:668-670.
  11. Lee JY. Severe 20-nail psoriasis successfully treated by low dose methotrexate. Dermatol Online J. 2009;15:8.
  12. Liao YC, Lee JY. Psoriasis in a 3-month-old infant with Kawasaki disease. Dermatol Online J. 2009;15:10.
  13. Khoo BP, Giam YC. A pilot study on the role of intralesional triamcinolone acetonide in the treatment of pitted nails in children. Singapore Med J. 2000;41:66-68.
  14. Piraccini BM, Tosti A, Iorizzo M, et al. Pustular psoriasis of the nails: treatment and long-term follow-up of 46 patients. Br J Dermatol. 2001;144:1000-1005.
  15. Diluvio L, Campione E, Paternò EJ, et al. Childhood nail psoriasis: a useful treatment with tazarotene 0.05%. Pediatr Dermatol. 2007;24:332-333.
  16. Teran CG, Teran-Escalera CN, Balderrama C. A severe case of erythrodermic psoriasis associated with advanced nail and joint manifestations: a case report. J Med Case Rep. 2010;4:179.
  17. Chen P, Li C, Xue R, et al. Efficacy and safety of acitretin monotherapy in children with pustular psoriasis: results from 15 cases and a literature review. J Dermatolog Treat. 2018;29:353-363.
  18. Wells LE, Evans T, Hilton R, et al. Use of secukinumab in a pediatric patient leads to significant improvement in nail psoriasis and psoriatic arthritis. Pediatr Dermatol. 2019;36:384-385.
  19. Watabe D, Endoh K, Maeda F, et al. Childhood-onset psoriatic onycho-pachydermo-periostitis treated successfully with infliximab. Eur J Dermatol. 2015;25:506-508. 
  20. Pereira TM, Vieira AP, Fernandes JC, et al. Anti-TNF-alpha therapy in childhood pustular psoriasis. Dermatology. 2006;213:350-352.
  21. Dini V, Barbanera S, Romanelli M. Efficacy of adalimumab for the treatment of refractory paediatric acrodermatitis continua of Hallopeau. Acta Derm Venereol. 2013;93:588-589.
  22. Kiszewski AE, De Villa D, Scheibel I, et al. An infant with acrodermatitis continua of Hallopeau: successful treatment with thalidomide and UVB therapy. Pediatr Dermatol. 2009;26:105-106.
  23. Bordignon M, Zattra E, Albertin C, et al. Successful treatment of a 9-year-old boy affected by acrodermatitis continua of Hallopeau with targeted ultraviolet B narrow-band phototherapy. Photodermatol Photoimmunol Photomed. 2010;26:41-43.
  24. Fabroni C, Gori A, Troiano M, et al. Infliximab efficacy in nail psoriasis. a retrospective study in 48 patients. J Eur Acad Dermatol Venereol. 2011;25:549-553.
  25. Lilly’s Taltz® (ixekizumab) receives U.S. FDA approval for the treatment of pediatric patients with moderate to severe plaque psoriasis. Eli Lilly and Company. March 30, 2020. Accessed September 24, 2021. https://investor.lilly.com/news-releases/news-release-details/lillys-taltzr-ixekizumab-receives-us-fda-approval-treatment-1
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From the University General Hospital of Patras, Greece. Drs. Plachouri and Georgiou are from the Department of Dermatology, and Dr. Mulita is from the Department of General Surgery.

The authors report no conflict of interest.

The eFigure is available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Kearse-Maria Plachouri, MD, PhD, University General Hospital of Patras, Rio 265 04, Greece ([email protected]).

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From the University General Hospital of Patras, Greece. Drs. Plachouri and Georgiou are from the Department of Dermatology, and Dr. Mulita is from the Department of General Surgery.

The authors report no conflict of interest.

The eFigure is available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Kearse-Maria Plachouri, MD, PhD, University General Hospital of Patras, Rio 265 04, Greece ([email protected]).

Author and Disclosure Information

From the University General Hospital of Patras, Greece. Drs. Plachouri and Georgiou are from the Department of Dermatology, and Dr. Mulita is from the Department of General Surgery.

The authors report no conflict of interest.

The eFigure is available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Kearse-Maria Plachouri, MD, PhD, University General Hospital of Patras, Rio 265 04, Greece ([email protected]).

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Pediatric nail psoriasis is a condition that has not been extensively studied. The prevalence of nail alterations in pediatric patients with psoriasis varies among different studies, ranging from 17% to 39.2%.1 Nail pitting, onycholysis associated with subungual hyperkeratosis, paronychia, and pachyonychia are the most frequent features of psoriatic nail involvement in children.2,3 The management of nail psoriasis in children and adolescents is critical due to the quality-of-life impact, from potential functional impairment issues to the obvious cosmetic problems, which can aggravate the psychologic distress and social embarrassment of patients with psoriasis. Despite the emergence of modern potent systemic agents to treat chronic plaque psoriasis, nail psoriasis often is refractory to treatment.4 Coupled with the limited on-label options for psoriasis treatment in children, the management of nail psoriasis in this special patient group constitutes an even greater therapeutic challenge. This report aims to summarize the limited existing data on the successful management of nail psoriasis in the pediatric population.

Reviewing the Literature on Nail Psoriasis

We conducted a search of PubMed articles indexed for MEDLINE, Embase, and Scopus using the following Medical Subject Headings key terms: nail psoriasis and children, juvenile, pediatric. Additional articles were identified from the reference lists of the retrieved articles and citations. Our search included reports in the English language published from 2000 to 2019. The selection process included the following 2 steps: screening of the titles and abstracts, followed by evaluation of the selected full-text articles.

Topical Treatments for Nail Psoriasis

Because most systemic antipsoriatic treatments that can be administered in adult patients have not yet been granted an official license for administration in children, topical treatments are considered by many physicians as the preferred first-line therapy for psoriatic nail involvement in pediatric patients.5,6 However, only scarce data are available in the literature concerning the successful use of local agents in pediatric patients with psoriasis.

The main limitation of local treatments relates mostly to their impaired penetration into the affected area (nails). To optimize drug penetration, some authors suggest the use of potent keratolytic topical preparations to reduce the nail volume and facilitate drug absorption.7 A popular suggestion is trimming the onycholytic nail plate followed by 40% urea avulsion to treat subungual hyperkeratosis8 or simply the use of occlusive 40% urea in petroleum jelly.9 Other approaches include clipping the onycholytic nail over the diseased nail bed or processing the nail plate through grinding or even drilling holes with the use of mechanical burrs or ablative lasers to enhance the penetration of the topical agent.7

A frequent approach in pediatric patients is clipping the detached nails combined with daily application of calcipotriene (calcipotriol) and steroids, such as betamethasone dipropionate.5,8 Reports on the use of regimens with clobetasol propionate ointment 0.05% under occlusion, with or without the concomitant use of calcipotriol solution 0.005%, also are present in the literature but not always with satisfactory results.10,11 Another successfully administered topical steroid is mometasone furoate cream 0.1%.12 Although the use of intralesional triamcinolone acetonide also has demonstrated encouraging outcomes in isolated reports,13 associated adverse events, such as pain and hematomas, can result in tolerability issues for pediatric patients.7

Piraccini et al14 described the case of an 8-year-old patient with pustular nail psoriasis who showed improvement within 3 to 6 months of treatment with topical calcipotriol 5 μg/g as monotherapy applied to the nail and periungual tissues twice daily. Another approach, described by Diluvio et al,15 is the use of tazarotene gel 0.05% applied once daily to the affected nail plates, nail folds, and periungual skin without occlusion. In a 6-year-old patient with isolated nail psoriasis, this treatment regimen demonstrated notable improvement within 8 weeks.15

Systemic Treatments for Nail Psoriasis

Data on the successful administration of systemic agents in pediatric patients also are extremely scarce. Due to the lack of clinical trials, everyday practice is mostly based on isolated case series and case reports.

 

 

Methotrexate—Lee11 described the case of an 11-year-old girl with severe, symptomatic, 20-nail psoriatic onychodystrophy who showed a complete response to oral methotrexate 5 mg/wk after topical clobetasol propionate and calcipotriol failed. Improvement was seen as early as 4 weeks after therapy initiation, and complete resolution of the lesions was documented after 9 and 13 months of methotrexate therapy for the fingers and toes, respectively.11 The successful use of methotrexate in the improvement of psoriatic nail dystrophy in a pediatric patient also was documented by Teran et al.16 In this case, a 9-year-old girl with erythrodermic psoriasis, psoriatic arthritis, and severe onychodystrophy showed notable amelioration of all psoriatic manifestations, including the nail findings, with systemic methotrexate therapy (dose not specified).16 Notably, the authors reported that the improvement of onychodystrophy occurred with considerable delay compared to the other psoriatic lesions,16 indicating the already-known refractoriness of nail psoriasis to the various therapeutic attempts.9-15

Acitretin—Another agent that has been linked with partial improvement of acrodermatitis continua of Hallopeau (ACH)–associated onychodystrophy is acitretin. In a case series of 15 pediatric patients with pustular psoriasis, a 5-year-old boy with severe nail involvement presented with partial amelioration of nail changes with acitretin within the first 6 weeks of treatment using the following regimen: initial dosage of 0.8 mg/kg/d for 6 weeks, followed by 0.3 mg/kg/d for 4 weeks.17

Biologics—The emerging use of biologics in pediatric psoriasis also has brought important advances in the successful management of nail psoriasis in children and adolescents.18-21 Wells et al18 presented the case of an 8-year-old girl with nail psoriasis, psoriatic arthritis, and plaque psoriasis who showed complete resolution of all psoriatic manifestations, including nail involvement, within 3 months of treatment with secukinumab 150 mg subcutaneously every 4 weeks. Prior failed treatments included various systemic agents (ie, subcutaneous methotrexate 20 mg/m2, etanercept 0.8 mg/kg weekly, adalimumab 40 mg every 2 weeks) as well as topical agents (ie, urea, tazarotene, corticosteroids) and intralesional triamcinolone.18

Infliximab also has been successfully used for pediatric nail psoriasis. Watabe et al19 presented the case of an 8-year-old girl with psoriatic onychodystrophy in addition to psoriatic onycho-pachydermo-periostitis. Prior therapy with adalimumab 20 mg every other week combined with methotrexate 10 mg weekly failed. She experienced notable amelioration of the nail dystrophy within 3 months of using a combination of infliximab and methotrexate (infliximab 5 mg/kg intravenously on weeks 0, 2, and 6, and every 8 weeks thereafter; methotrexate 10 mg/wk).19

Cases in which infliximab has resulted in rapid yet only transient restoration of psoriatic onychodystrophy also are present in the literature. Pereira et al20 reported that a 3-year-old patient with severe 20-digit onychodystrophy in addition to pustular psoriasis had complete resolution of nail lesions within 2 weeks of treatment with infliximab (5 mg/kg at weeks 0, 2, and 6, and then every 7 weeks thereafter), which was sustained over the course of 1 year. The therapy had to be discontinued because of exacerbation of the cutaneous symptoms; thereafter, etanercept was initiated. Although the patient noted major improvement of all skin lesions under etanercept, only moderate amelioration of the psoriatic nail lesions was demonstrated.20

 

 

Dini et al21 described a 9-year-old girl with severe ACH-associated psoriatic onychodystrophy who showed complete clearance of all lesions within 8 weeks of treatment with adalimumab (initially 80 mg, followed by 40 mg after 1 week and then 40 mg every other week). Prior treatment with potent topical corticosteroids, cyclosporine (3 mg/kg/d for 6 months), and etanercept (0.4 mg/kg twice weekly for 3 months) was ineffective.21

Phototherapy—Other systemic agents with reported satisfactory outcomes in the treatment of psoriatic onychodystrophy include thalidomide combined with UVB phototherapy. Kiszewski et al22 described a 2-year-old patient with ACH and severe 19-digit onychodystrophy. Prior failed therapies included occluded clobetasol ointment 0.05%, occluded pimecrolimus 0.1%, and systemic methotrexate, while systemic acitretin (0.8 mg⁄kg⁄d) resulted in elevated cholesterol levels and therefore had to be interrupted. Improvement was seen 2 months after the initiation of a combined broadband UVB and thalidomide (50 mg⁄d) treatment, with no documented relapses after discontinuation of therapy.22

Narrowband UVB (311 nm) also has been used as monotherapy for ACH-associated onychodystrophy, as demonstrated by Bordignon et al.23 They reported a 9-year-old patient who showed partial improvement of isolated onychodystrophy of the fourth nail plate of the left hand after 36 sessions of narrowband UVB using a 311-nm filtering handpiece with a square spot size of 19×19 mm.23

Conclusion

Nail psoriasis constitutes a type of psoriasis that is not only refractory to most treatments but is accompanied by substantial psychological and occasionally functional burden for the affected individuals.24 Data concerning therapeutic options in the pediatric population are extremely limited, and therefore the everyday practice often involves administration of off-label medications, which can constitute a dilemma for many physicians, especially for safety.10 We suggest a simple therapeutic algorithm for the management of pediatric nail psoriasis based on the summarized data that are currently available in the literature. This algorithm is shown in the eFigure.

eFIGURE. Proposed algorithm for the management of nail psoriasis in children.

As progressively more agents—especially biologics—receive approval for use in plaque psoriasis in pediatric patients,25 it is expected that gradually more real-life data on their side efficacy for plaque psoriasis of the nails in children also will come to light. Furthermore, their on-label use in pediatric psoriasis patients will facilitate further relevant clinical trials to this target group so that the potential of these medications in the management of nail psoriasis can be fully explored.

Pediatric nail psoriasis is a condition that has not been extensively studied. The prevalence of nail alterations in pediatric patients with psoriasis varies among different studies, ranging from 17% to 39.2%.1 Nail pitting, onycholysis associated with subungual hyperkeratosis, paronychia, and pachyonychia are the most frequent features of psoriatic nail involvement in children.2,3 The management of nail psoriasis in children and adolescents is critical due to the quality-of-life impact, from potential functional impairment issues to the obvious cosmetic problems, which can aggravate the psychologic distress and social embarrassment of patients with psoriasis. Despite the emergence of modern potent systemic agents to treat chronic plaque psoriasis, nail psoriasis often is refractory to treatment.4 Coupled with the limited on-label options for psoriasis treatment in children, the management of nail psoriasis in this special patient group constitutes an even greater therapeutic challenge. This report aims to summarize the limited existing data on the successful management of nail psoriasis in the pediatric population.

Reviewing the Literature on Nail Psoriasis

We conducted a search of PubMed articles indexed for MEDLINE, Embase, and Scopus using the following Medical Subject Headings key terms: nail psoriasis and children, juvenile, pediatric. Additional articles were identified from the reference lists of the retrieved articles and citations. Our search included reports in the English language published from 2000 to 2019. The selection process included the following 2 steps: screening of the titles and abstracts, followed by evaluation of the selected full-text articles.

Topical Treatments for Nail Psoriasis

Because most systemic antipsoriatic treatments that can be administered in adult patients have not yet been granted an official license for administration in children, topical treatments are considered by many physicians as the preferred first-line therapy for psoriatic nail involvement in pediatric patients.5,6 However, only scarce data are available in the literature concerning the successful use of local agents in pediatric patients with psoriasis.

The main limitation of local treatments relates mostly to their impaired penetration into the affected area (nails). To optimize drug penetration, some authors suggest the use of potent keratolytic topical preparations to reduce the nail volume and facilitate drug absorption.7 A popular suggestion is trimming the onycholytic nail plate followed by 40% urea avulsion to treat subungual hyperkeratosis8 or simply the use of occlusive 40% urea in petroleum jelly.9 Other approaches include clipping the onycholytic nail over the diseased nail bed or processing the nail plate through grinding or even drilling holes with the use of mechanical burrs or ablative lasers to enhance the penetration of the topical agent.7

A frequent approach in pediatric patients is clipping the detached nails combined with daily application of calcipotriene (calcipotriol) and steroids, such as betamethasone dipropionate.5,8 Reports on the use of regimens with clobetasol propionate ointment 0.05% under occlusion, with or without the concomitant use of calcipotriol solution 0.005%, also are present in the literature but not always with satisfactory results.10,11 Another successfully administered topical steroid is mometasone furoate cream 0.1%.12 Although the use of intralesional triamcinolone acetonide also has demonstrated encouraging outcomes in isolated reports,13 associated adverse events, such as pain and hematomas, can result in tolerability issues for pediatric patients.7

Piraccini et al14 described the case of an 8-year-old patient with pustular nail psoriasis who showed improvement within 3 to 6 months of treatment with topical calcipotriol 5 μg/g as monotherapy applied to the nail and periungual tissues twice daily. Another approach, described by Diluvio et al,15 is the use of tazarotene gel 0.05% applied once daily to the affected nail plates, nail folds, and periungual skin without occlusion. In a 6-year-old patient with isolated nail psoriasis, this treatment regimen demonstrated notable improvement within 8 weeks.15

Systemic Treatments for Nail Psoriasis

Data on the successful administration of systemic agents in pediatric patients also are extremely scarce. Due to the lack of clinical trials, everyday practice is mostly based on isolated case series and case reports.

 

 

Methotrexate—Lee11 described the case of an 11-year-old girl with severe, symptomatic, 20-nail psoriatic onychodystrophy who showed a complete response to oral methotrexate 5 mg/wk after topical clobetasol propionate and calcipotriol failed. Improvement was seen as early as 4 weeks after therapy initiation, and complete resolution of the lesions was documented after 9 and 13 months of methotrexate therapy for the fingers and toes, respectively.11 The successful use of methotrexate in the improvement of psoriatic nail dystrophy in a pediatric patient also was documented by Teran et al.16 In this case, a 9-year-old girl with erythrodermic psoriasis, psoriatic arthritis, and severe onychodystrophy showed notable amelioration of all psoriatic manifestations, including the nail findings, with systemic methotrexate therapy (dose not specified).16 Notably, the authors reported that the improvement of onychodystrophy occurred with considerable delay compared to the other psoriatic lesions,16 indicating the already-known refractoriness of nail psoriasis to the various therapeutic attempts.9-15

Acitretin—Another agent that has been linked with partial improvement of acrodermatitis continua of Hallopeau (ACH)–associated onychodystrophy is acitretin. In a case series of 15 pediatric patients with pustular psoriasis, a 5-year-old boy with severe nail involvement presented with partial amelioration of nail changes with acitretin within the first 6 weeks of treatment using the following regimen: initial dosage of 0.8 mg/kg/d for 6 weeks, followed by 0.3 mg/kg/d for 4 weeks.17

Biologics—The emerging use of biologics in pediatric psoriasis also has brought important advances in the successful management of nail psoriasis in children and adolescents.18-21 Wells et al18 presented the case of an 8-year-old girl with nail psoriasis, psoriatic arthritis, and plaque psoriasis who showed complete resolution of all psoriatic manifestations, including nail involvement, within 3 months of treatment with secukinumab 150 mg subcutaneously every 4 weeks. Prior failed treatments included various systemic agents (ie, subcutaneous methotrexate 20 mg/m2, etanercept 0.8 mg/kg weekly, adalimumab 40 mg every 2 weeks) as well as topical agents (ie, urea, tazarotene, corticosteroids) and intralesional triamcinolone.18

Infliximab also has been successfully used for pediatric nail psoriasis. Watabe et al19 presented the case of an 8-year-old girl with psoriatic onychodystrophy in addition to psoriatic onycho-pachydermo-periostitis. Prior therapy with adalimumab 20 mg every other week combined with methotrexate 10 mg weekly failed. She experienced notable amelioration of the nail dystrophy within 3 months of using a combination of infliximab and methotrexate (infliximab 5 mg/kg intravenously on weeks 0, 2, and 6, and every 8 weeks thereafter; methotrexate 10 mg/wk).19

Cases in which infliximab has resulted in rapid yet only transient restoration of psoriatic onychodystrophy also are present in the literature. Pereira et al20 reported that a 3-year-old patient with severe 20-digit onychodystrophy in addition to pustular psoriasis had complete resolution of nail lesions within 2 weeks of treatment with infliximab (5 mg/kg at weeks 0, 2, and 6, and then every 7 weeks thereafter), which was sustained over the course of 1 year. The therapy had to be discontinued because of exacerbation of the cutaneous symptoms; thereafter, etanercept was initiated. Although the patient noted major improvement of all skin lesions under etanercept, only moderate amelioration of the psoriatic nail lesions was demonstrated.20

 

 

Dini et al21 described a 9-year-old girl with severe ACH-associated psoriatic onychodystrophy who showed complete clearance of all lesions within 8 weeks of treatment with adalimumab (initially 80 mg, followed by 40 mg after 1 week and then 40 mg every other week). Prior treatment with potent topical corticosteroids, cyclosporine (3 mg/kg/d for 6 months), and etanercept (0.4 mg/kg twice weekly for 3 months) was ineffective.21

Phototherapy—Other systemic agents with reported satisfactory outcomes in the treatment of psoriatic onychodystrophy include thalidomide combined with UVB phototherapy. Kiszewski et al22 described a 2-year-old patient with ACH and severe 19-digit onychodystrophy. Prior failed therapies included occluded clobetasol ointment 0.05%, occluded pimecrolimus 0.1%, and systemic methotrexate, while systemic acitretin (0.8 mg⁄kg⁄d) resulted in elevated cholesterol levels and therefore had to be interrupted. Improvement was seen 2 months after the initiation of a combined broadband UVB and thalidomide (50 mg⁄d) treatment, with no documented relapses after discontinuation of therapy.22

Narrowband UVB (311 nm) also has been used as monotherapy for ACH-associated onychodystrophy, as demonstrated by Bordignon et al.23 They reported a 9-year-old patient who showed partial improvement of isolated onychodystrophy of the fourth nail plate of the left hand after 36 sessions of narrowband UVB using a 311-nm filtering handpiece with a square spot size of 19×19 mm.23

Conclusion

Nail psoriasis constitutes a type of psoriasis that is not only refractory to most treatments but is accompanied by substantial psychological and occasionally functional burden for the affected individuals.24 Data concerning therapeutic options in the pediatric population are extremely limited, and therefore the everyday practice often involves administration of off-label medications, which can constitute a dilemma for many physicians, especially for safety.10 We suggest a simple therapeutic algorithm for the management of pediatric nail psoriasis based on the summarized data that are currently available in the literature. This algorithm is shown in the eFigure.

eFIGURE. Proposed algorithm for the management of nail psoriasis in children.

As progressively more agents—especially biologics—receive approval for use in plaque psoriasis in pediatric patients,25 it is expected that gradually more real-life data on their side efficacy for plaque psoriasis of the nails in children also will come to light. Furthermore, their on-label use in pediatric psoriasis patients will facilitate further relevant clinical trials to this target group so that the potential of these medications in the management of nail psoriasis can be fully explored.

References
  1. Uber M, Carvalho VO, Abagge KT, et al. Clinical features and nail clippings in 52 children with psoriasis. Pediatr Dermatol. 2018;35:202-207.
  2. Pourchot D, Bodemer C, Phan A, et al. Nail psoriasis: a systematic evaluation in 313 children with psoriasis. Pediatr Dermatol. 2017;34:58-63.
  3. Piraccini BM, Triantafyllopoulou I, Prevezas C, et al. Nail psoriasis in children: common or uncommon? results from a 10-year double-center study. Skin Appendage Disord. 2015;1:43-48.
  4. Baran R. The burden of nail psoriasis: an introduction. Dermatology. 2010;221(suppl 1):1-5.
  5. Richert B, André J. Nail disorders in children: diagnosis and management. Am J Clin Dermatol. 2011;12:101-112.
  6. Trüeb RM. Therapies for childhood psoriasis. Curr Probl Dermatol. 2009;38:137-159.
  7. Haneke E. Nail psoriasis: clinical features, pathogenesis, differential diagnoses, and management. Psoriasis (Auckl). 2017;7:51-63.
  8. Piraccini BM, Starace M. Nail disorders in infants and children. Curr Opin Pediatr. 2014;26:440-445.
  9. Duran-McKinster C, Ortiz-Solis D, Granados J, et al. Juvenile psoriatic arthritis with nail psoriasis in the absence of cutaneous lesions. Int J Dermatol. 2000;39:32-35.
  10. Holzberg M, Ruben BS, Baran R. Psoriasis restricted to the nail in a 7-year-old child. should biologics be an appropriate treatment modality when considering quality of life? J Eur Acad Dermatol Venereol. 2014;28:668-670.
  11. Lee JY. Severe 20-nail psoriasis successfully treated by low dose methotrexate. Dermatol Online J. 2009;15:8.
  12. Liao YC, Lee JY. Psoriasis in a 3-month-old infant with Kawasaki disease. Dermatol Online J. 2009;15:10.
  13. Khoo BP, Giam YC. A pilot study on the role of intralesional triamcinolone acetonide in the treatment of pitted nails in children. Singapore Med J. 2000;41:66-68.
  14. Piraccini BM, Tosti A, Iorizzo M, et al. Pustular psoriasis of the nails: treatment and long-term follow-up of 46 patients. Br J Dermatol. 2001;144:1000-1005.
  15. Diluvio L, Campione E, Paternò EJ, et al. Childhood nail psoriasis: a useful treatment with tazarotene 0.05%. Pediatr Dermatol. 2007;24:332-333.
  16. Teran CG, Teran-Escalera CN, Balderrama C. A severe case of erythrodermic psoriasis associated with advanced nail and joint manifestations: a case report. J Med Case Rep. 2010;4:179.
  17. Chen P, Li C, Xue R, et al. Efficacy and safety of acitretin monotherapy in children with pustular psoriasis: results from 15 cases and a literature review. J Dermatolog Treat. 2018;29:353-363.
  18. Wells LE, Evans T, Hilton R, et al. Use of secukinumab in a pediatric patient leads to significant improvement in nail psoriasis and psoriatic arthritis. Pediatr Dermatol. 2019;36:384-385.
  19. Watabe D, Endoh K, Maeda F, et al. Childhood-onset psoriatic onycho-pachydermo-periostitis treated successfully with infliximab. Eur J Dermatol. 2015;25:506-508. 
  20. Pereira TM, Vieira AP, Fernandes JC, et al. Anti-TNF-alpha therapy in childhood pustular psoriasis. Dermatology. 2006;213:350-352.
  21. Dini V, Barbanera S, Romanelli M. Efficacy of adalimumab for the treatment of refractory paediatric acrodermatitis continua of Hallopeau. Acta Derm Venereol. 2013;93:588-589.
  22. Kiszewski AE, De Villa D, Scheibel I, et al. An infant with acrodermatitis continua of Hallopeau: successful treatment with thalidomide and UVB therapy. Pediatr Dermatol. 2009;26:105-106.
  23. Bordignon M, Zattra E, Albertin C, et al. Successful treatment of a 9-year-old boy affected by acrodermatitis continua of Hallopeau with targeted ultraviolet B narrow-band phototherapy. Photodermatol Photoimmunol Photomed. 2010;26:41-43.
  24. Fabroni C, Gori A, Troiano M, et al. Infliximab efficacy in nail psoriasis. a retrospective study in 48 patients. J Eur Acad Dermatol Venereol. 2011;25:549-553.
  25. Lilly’s Taltz® (ixekizumab) receives U.S. FDA approval for the treatment of pediatric patients with moderate to severe plaque psoriasis. Eli Lilly and Company. March 30, 2020. Accessed September 24, 2021. https://investor.lilly.com/news-releases/news-release-details/lillys-taltzr-ixekizumab-receives-us-fda-approval-treatment-1
References
  1. Uber M, Carvalho VO, Abagge KT, et al. Clinical features and nail clippings in 52 children with psoriasis. Pediatr Dermatol. 2018;35:202-207.
  2. Pourchot D, Bodemer C, Phan A, et al. Nail psoriasis: a systematic evaluation in 313 children with psoriasis. Pediatr Dermatol. 2017;34:58-63.
  3. Piraccini BM, Triantafyllopoulou I, Prevezas C, et al. Nail psoriasis in children: common or uncommon? results from a 10-year double-center study. Skin Appendage Disord. 2015;1:43-48.
  4. Baran R. The burden of nail psoriasis: an introduction. Dermatology. 2010;221(suppl 1):1-5.
  5. Richert B, André J. Nail disorders in children: diagnosis and management. Am J Clin Dermatol. 2011;12:101-112.
  6. Trüeb RM. Therapies for childhood psoriasis. Curr Probl Dermatol. 2009;38:137-159.
  7. Haneke E. Nail psoriasis: clinical features, pathogenesis, differential diagnoses, and management. Psoriasis (Auckl). 2017;7:51-63.
  8. Piraccini BM, Starace M. Nail disorders in infants and children. Curr Opin Pediatr. 2014;26:440-445.
  9. Duran-McKinster C, Ortiz-Solis D, Granados J, et al. Juvenile psoriatic arthritis with nail psoriasis in the absence of cutaneous lesions. Int J Dermatol. 2000;39:32-35.
  10. Holzberg M, Ruben BS, Baran R. Psoriasis restricted to the nail in a 7-year-old child. should biologics be an appropriate treatment modality when considering quality of life? J Eur Acad Dermatol Venereol. 2014;28:668-670.
  11. Lee JY. Severe 20-nail psoriasis successfully treated by low dose methotrexate. Dermatol Online J. 2009;15:8.
  12. Liao YC, Lee JY. Psoriasis in a 3-month-old infant with Kawasaki disease. Dermatol Online J. 2009;15:10.
  13. Khoo BP, Giam YC. A pilot study on the role of intralesional triamcinolone acetonide in the treatment of pitted nails in children. Singapore Med J. 2000;41:66-68.
  14. Piraccini BM, Tosti A, Iorizzo M, et al. Pustular psoriasis of the nails: treatment and long-term follow-up of 46 patients. Br J Dermatol. 2001;144:1000-1005.
  15. Diluvio L, Campione E, Paternò EJ, et al. Childhood nail psoriasis: a useful treatment with tazarotene 0.05%. Pediatr Dermatol. 2007;24:332-333.
  16. Teran CG, Teran-Escalera CN, Balderrama C. A severe case of erythrodermic psoriasis associated with advanced nail and joint manifestations: a case report. J Med Case Rep. 2010;4:179.
  17. Chen P, Li C, Xue R, et al. Efficacy and safety of acitretin monotherapy in children with pustular psoriasis: results from 15 cases and a literature review. J Dermatolog Treat. 2018;29:353-363.
  18. Wells LE, Evans T, Hilton R, et al. Use of secukinumab in a pediatric patient leads to significant improvement in nail psoriasis and psoriatic arthritis. Pediatr Dermatol. 2019;36:384-385.
  19. Watabe D, Endoh K, Maeda F, et al. Childhood-onset psoriatic onycho-pachydermo-periostitis treated successfully with infliximab. Eur J Dermatol. 2015;25:506-508. 
  20. Pereira TM, Vieira AP, Fernandes JC, et al. Anti-TNF-alpha therapy in childhood pustular psoriasis. Dermatology. 2006;213:350-352.
  21. Dini V, Barbanera S, Romanelli M. Efficacy of adalimumab for the treatment of refractory paediatric acrodermatitis continua of Hallopeau. Acta Derm Venereol. 2013;93:588-589.
  22. Kiszewski AE, De Villa D, Scheibel I, et al. An infant with acrodermatitis continua of Hallopeau: successful treatment with thalidomide and UVB therapy. Pediatr Dermatol. 2009;26:105-106.
  23. Bordignon M, Zattra E, Albertin C, et al. Successful treatment of a 9-year-old boy affected by acrodermatitis continua of Hallopeau with targeted ultraviolet B narrow-band phototherapy. Photodermatol Photoimmunol Photomed. 2010;26:41-43.
  24. Fabroni C, Gori A, Troiano M, et al. Infliximab efficacy in nail psoriasis. a retrospective study in 48 patients. J Eur Acad Dermatol Venereol. 2011;25:549-553.
  25. Lilly’s Taltz® (ixekizumab) receives U.S. FDA approval for the treatment of pediatric patients with moderate to severe plaque psoriasis. Eli Lilly and Company. March 30, 2020. Accessed September 24, 2021. https://investor.lilly.com/news-releases/news-release-details/lillys-taltzr-ixekizumab-receives-us-fda-approval-treatment-1
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  • No clinical trials assessing the management of pediatric nail psoriasis currently are present in the literature. Limited information on the treatment of pediatric nail psoriasis exists, mostly in the form of small case series and case reports.
  • As more agents are approved for on-label use in plaque psoriasis in pediatric patients, gradually more real-life data on their efficacy for nail psoriasis in children are expected to come to light.
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Clinical Edge Journal Scan Commentary: Psoriasis November 2021

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Dr. Ferris scans the journals, so you don’t have to!

Laura Ferris, MD, PhD
There are several therapeutic options for patients with psoriasis with established safety and efficacy based on large clinical trials. In general, these studies are performed under stringent conditions, using validated clinician-performed outcomes such as the psoriasis area and severity index (PASI), investigator’s global assessment (IGA), and/or body surface area (BSA). Patients with significant comorbidities or who have failed several previous therapies are often excluded from participating in such studies. It is thus important to understand how therapies perform in the real world and in-patient populations other than those studied in registrational trials.

Biologic therapy is generally reserved for patients with more moderate-to-severe psoriasis, often defined as BSA ≥10% or PASI of ≥10. Notably, these criteria are all clinician-performed. The Dermatology Life Quality Index (DLQI) measures the impact of the disease on the patient with a score of 0-5, 6-10, and 11-30 indicating mild, moderate, and severe disease, respectively. In a cross-sectional, observational study, 72.4% of psoriasis patients who qualified for systemic therapy initiation based on PASI and/or BSA had a DLQI of less than 10. Conversely, 10.4% of patients with a DLQI score higher than 10 did not qualify for systemic therapy based on PASI and/or BSA. This study highlights the complementary value of considering both clinician and patient determinants of disease severity when choosing a psoriasis therapy (Barbieri JS et al.)

With so many therapeutic options, it is increasingly common for patients to switch from one biologic to another. Many factors that go into the decision to switch therapies. A retrospective study of 115 adult patients with psoriasis found that the primary factor driving switching was lack of sufficient efficacy in treating skin disease. Having concomitant psoriatic arthritis increased the likelihood of switching by 2.69-fold (Akdogan N et al.). These findings suggest that shared decision making with dermatology, rheumatology, and the patient may help in choosing a treatment plan that best addresses both skin and joints.

One consideration when counseling patients about their likelihood of response to a second or third biologic is that in several clinical trials, biologic-naïve patients tend to have higher PASI responses to biologics than do heavier and biologic-experienced patients. A recent retrospective study found that receiving one or more biologic receiving was associated with a lower likelihood of achieving a PASI75 response to guselkumab (Hung YT et al.). However, in a real-life multicenter study including 57 adult patients with moderate-to-severe psoriasis receiving risankizumab, more biologic-experienced patients reached PASI 100 at weeks 36 and 52 (71.8% and 69.2%, respectively) compared with biologic-naïve patients (50.0% and 37.5%, respectively) (Gerdes S et al.). While both studies were small and no firm conclusions or comparisons can be drawn, real-world data from large multicenter studies that evaluate multiple therapies may guide us in choosing the best therapy for challenging patients who are often underrepresented in clinical trials. Understanding how switching within vs. between classes (TNF, IL-17, and IL-23 inhibitors) impacts efficacy will also help in making choices about biologic switches.

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Laura K. Ferris, MD, PhD, Professor, Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania

Laura K. Ferris, MD, PhD, has disclosed the following relevant financial relationships:

Received income in an amount equal to or greater than $250 from: Eli Lilly; Janssen; Bristol-Myers Squibb; Arcutis; Dermavant; AbbVie

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Laura K. Ferris, MD, PhD, Professor, Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania

Laura K. Ferris, MD, PhD, has disclosed the following relevant financial relationships:

Received income in an amount equal to or greater than $250 from: Eli Lilly; Janssen; Bristol-Myers Squibb; Arcutis; Dermavant; AbbVie

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Laura K. Ferris, MD, PhD, Professor, Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania

Laura K. Ferris, MD, PhD, has disclosed the following relevant financial relationships:

Received income in an amount equal to or greater than $250 from: Eli Lilly; Janssen; Bristol-Myers Squibb; Arcutis; Dermavant; AbbVie

Dr. Ferris scans the journals, so you don’t have to!
Dr. Ferris scans the journals, so you don’t have to!

Laura Ferris, MD, PhD
There are several therapeutic options for patients with psoriasis with established safety and efficacy based on large clinical trials. In general, these studies are performed under stringent conditions, using validated clinician-performed outcomes such as the psoriasis area and severity index (PASI), investigator’s global assessment (IGA), and/or body surface area (BSA). Patients with significant comorbidities or who have failed several previous therapies are often excluded from participating in such studies. It is thus important to understand how therapies perform in the real world and in-patient populations other than those studied in registrational trials.

Biologic therapy is generally reserved for patients with more moderate-to-severe psoriasis, often defined as BSA ≥10% or PASI of ≥10. Notably, these criteria are all clinician-performed. The Dermatology Life Quality Index (DLQI) measures the impact of the disease on the patient with a score of 0-5, 6-10, and 11-30 indicating mild, moderate, and severe disease, respectively. In a cross-sectional, observational study, 72.4% of psoriasis patients who qualified for systemic therapy initiation based on PASI and/or BSA had a DLQI of less than 10. Conversely, 10.4% of patients with a DLQI score higher than 10 did not qualify for systemic therapy based on PASI and/or BSA. This study highlights the complementary value of considering both clinician and patient determinants of disease severity when choosing a psoriasis therapy (Barbieri JS et al.)

With so many therapeutic options, it is increasingly common for patients to switch from one biologic to another. Many factors that go into the decision to switch therapies. A retrospective study of 115 adult patients with psoriasis found that the primary factor driving switching was lack of sufficient efficacy in treating skin disease. Having concomitant psoriatic arthritis increased the likelihood of switching by 2.69-fold (Akdogan N et al.). These findings suggest that shared decision making with dermatology, rheumatology, and the patient may help in choosing a treatment plan that best addresses both skin and joints.

One consideration when counseling patients about their likelihood of response to a second or third biologic is that in several clinical trials, biologic-naïve patients tend to have higher PASI responses to biologics than do heavier and biologic-experienced patients. A recent retrospective study found that receiving one or more biologic receiving was associated with a lower likelihood of achieving a PASI75 response to guselkumab (Hung YT et al.). However, in a real-life multicenter study including 57 adult patients with moderate-to-severe psoriasis receiving risankizumab, more biologic-experienced patients reached PASI 100 at weeks 36 and 52 (71.8% and 69.2%, respectively) compared with biologic-naïve patients (50.0% and 37.5%, respectively) (Gerdes S et al.). While both studies were small and no firm conclusions or comparisons can be drawn, real-world data from large multicenter studies that evaluate multiple therapies may guide us in choosing the best therapy for challenging patients who are often underrepresented in clinical trials. Understanding how switching within vs. between classes (TNF, IL-17, and IL-23 inhibitors) impacts efficacy will also help in making choices about biologic switches.

Laura Ferris, MD, PhD
There are several therapeutic options for patients with psoriasis with established safety and efficacy based on large clinical trials. In general, these studies are performed under stringent conditions, using validated clinician-performed outcomes such as the psoriasis area and severity index (PASI), investigator’s global assessment (IGA), and/or body surface area (BSA). Patients with significant comorbidities or who have failed several previous therapies are often excluded from participating in such studies. It is thus important to understand how therapies perform in the real world and in-patient populations other than those studied in registrational trials.

Biologic therapy is generally reserved for patients with more moderate-to-severe psoriasis, often defined as BSA ≥10% or PASI of ≥10. Notably, these criteria are all clinician-performed. The Dermatology Life Quality Index (DLQI) measures the impact of the disease on the patient with a score of 0-5, 6-10, and 11-30 indicating mild, moderate, and severe disease, respectively. In a cross-sectional, observational study, 72.4% of psoriasis patients who qualified for systemic therapy initiation based on PASI and/or BSA had a DLQI of less than 10. Conversely, 10.4% of patients with a DLQI score higher than 10 did not qualify for systemic therapy based on PASI and/or BSA. This study highlights the complementary value of considering both clinician and patient determinants of disease severity when choosing a psoriasis therapy (Barbieri JS et al.)

With so many therapeutic options, it is increasingly common for patients to switch from one biologic to another. Many factors that go into the decision to switch therapies. A retrospective study of 115 adult patients with psoriasis found that the primary factor driving switching was lack of sufficient efficacy in treating skin disease. Having concomitant psoriatic arthritis increased the likelihood of switching by 2.69-fold (Akdogan N et al.). These findings suggest that shared decision making with dermatology, rheumatology, and the patient may help in choosing a treatment plan that best addresses both skin and joints.

One consideration when counseling patients about their likelihood of response to a second or third biologic is that in several clinical trials, biologic-naïve patients tend to have higher PASI responses to biologics than do heavier and biologic-experienced patients. A recent retrospective study found that receiving one or more biologic receiving was associated with a lower likelihood of achieving a PASI75 response to guselkumab (Hung YT et al.). However, in a real-life multicenter study including 57 adult patients with moderate-to-severe psoriasis receiving risankizumab, more biologic-experienced patients reached PASI 100 at weeks 36 and 52 (71.8% and 69.2%, respectively) compared with biologic-naïve patients (50.0% and 37.5%, respectively) (Gerdes S et al.). While both studies were small and no firm conclusions or comparisons can be drawn, real-world data from large multicenter studies that evaluate multiple therapies may guide us in choosing the best therapy for challenging patients who are often underrepresented in clinical trials. Understanding how switching within vs. between classes (TNF, IL-17, and IL-23 inhibitors) impacts efficacy will also help in making choices about biologic switches.

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