Genital psoriasis

A review of sexual dysfunction in psoriasis with a focus on genital involvement. Genital psoriasis: Prevalence, Impact , Treatment
Increased recognition?

1. Genital Psoriasis Sexual dysfunction in psoriasis Genital psoriasis Prevalence Impact Treatment Increased recognition? 1 By Mats Lundstrom, Medical Science Liaison, May 2021 Vancouver, Canada

2. Sexual Dysfunction in Psoriasis P soriasis patients have a higher risk of sexual dysfunction as compared to the general population.  1 However, data on the sexual difficulties of patients with psoriasis are scarce 6 . 40% o f patients answered yes to the question “Do you believe that since the onset of psoriasis your sexual activity has declined?” (a fter controlling for potential confounders such as alcohol consumption and depression). 2 Sexual dysfunction was found in 48.7% of British women with psoriasis evaluated using the FSFI All the domains of the FSFI except lubrication and pain appear to be significantly affected; of all the domains, sexual desire may be the one most affected 3 . Sexual dysfunction was found in 58.6% of Brazilian women with psoriasis 4 . International Index of Erectile Function (IIEF) is often used to evaluate male sexual function. A study produced a score of 55.7 ± 17.2 (the index ranges from 5–75, and the higher the score, the better the sexual function), with no statistically significant difference between the groups with and without genital lesion 3 . O ne study found erectile dysfunction in 56% of individuals with mild psoriasis, in 46.6% of those with the severe form of the disease, and in 23.3% of a control group. Most patients with sexual dysfunction in this study had genital lesions 5 . 2 1) Molina-Leyva et al. Sexual dysfunction in psoriasis: a systematic review. J Eur Acad Dermatol Venereol . 2015 Apr;29(4):649-55 2) Gupta, M.A. and Gupta, A.K. (1997), Psoriasis and sex: a study of moderately to severely affected patients. International Journal of Dermatology, 36: 259-262. 3 ) Duarte et al . Psoriasis and sexual dysfunction: links, risks, and management challenges.  Psoriasis ( Auckl ) . 2018;8:93-99. Published 2018 Dec 10. 4) Kurizky PS, Martins GA, Carneiro JN, Gomes CM, Mota LMHD. Evaluation of the occurrence of sexual dysfunction and general quality of life in female patients with psoriasis. An Bras Dermatol. 2018;93(6):801-806. 5) Bardazzi et al Sex and the PASI: patients affected by a mild form of psoriasis are more predisposed to have a more severe form of erectile dysfunction. J Eur Acad Dermatol Venereol . 2016 Aug;30(8):1342-8. 6) Kurizky et al.. Sexual dysfunction in patients with psoriasis and psoriatic arthritis--a systematic review. Rev Bras Reumatol . 2012 Dec;52(6):943-8. English, Portuguese.

3. Sexual Dysfunction in Psoriasis is Multifactorial Suggested Factors: Detrimental effect of the condition on the individual’s physical appearance and the psychosocial effects of this. C oncerns of the sexual partner 1 . Rejection because of psoriasis is experienced by 44.7% of men and feeling unattractive or embarrassed during psoriasis exacerbation can aggravate low self-confidence and erectile dysfunction 2 Side effects of the medical treatments for psoriasis 1 . Decreased libido and the inconvenience caused both by skin desquamation and by topical treatment 1 . Physical signs and symptoms such as stinging, bleeding, and desquamation 1 Psychological disease as depression and anxiety. Joint involvement, the severity of pruritus, and higher depression scores have all been reported to be associated with impaired sexual function 1 Sedentary lifestyle and associated comorbidities such as dyslipidemia, hypertension, diabetes, obesity, metabolic syndrome, and depression. This increases risk of erectile dysfunction. 1 3 1) Duarte et al . Psoriasis and sexual dysfunction: links, risks, and management challenges.  Psoriasis ( Auckl ) . 2018;8:93-99. Published 2018 Dec 10. 2) Wojciechowska-Zdrojowy et al. Analysis of sexual problems in men with psoriasis. J Sex Marital Ther . 2018 Apr 12

4. Incidence of Genital Psoriasis Genital psoriasis is found in about 30 – 40% of patients with psoriasis and is more common in men 1 . Genital skin involvement concerns approximately 63% of patients with psoriasis during the course of disease and up to 79% of patients with inverse psoriasis 1,2 . Genital involvement remains often undiagnosed and untreated 1 . Despite the high prevalence of genital psoriasis, almost half of patients with genital lesions do not discuss their symptoms with their physician 2 Over two-thirds of patients with genital psoriasis have never applied treatment to their genitals. 45% of patients who discussed genital lesions with their physician reported not receiving treatment. 3 4 1 ) Merola et al. Underdiagnosed and undertreated psoriasis: Nuances of treating psoriasis affecting the scalp, face, intertriginous areas, genitals, hands, feet, and nails. Dermatol Ther . 2018 May;31(3):e12589. 2) Beck KM et al. Treatment of Genital Psoriasis: A Systematic Review.  Dermatol Ther ( Heidelb ) . 2018;8(4):509-525. 3) Meeuwis et al. Patients' experience of psoriasis in the genital area. Dermatology. 2012;224(3):271-6.

5. 5 A difference of 4.7 in DLQI Yang et.al The impact of genital psoriasis on quality of life: a systematic review. Psoriasis ( Auckl ). 2018 Aug 28;8:41-47. An improvement of 4.1 points in DLQI with treatment Genital Psoriasis Impact on QoL

6. 20 Patients screened at a dermatology clini c Physician diagnosis of chronic plaque psoriasis (> 6 months duration) Current or recent history (within 3 months) of moderate or severe genital involvement (per Patient Global Assessment > 4, 6-point scale from 0 to 5) Confirmation by a dermatologist of overall psoriasis, affected body surface area ≥1%, and plaque psoriasis in extragenital areas. Intolerance of or failure to respond to >1 topical therapy, which included over-the-counter topicals, for Genital Psoriasis. Cather JC, Ryan C, Meeuwis K et. al. Patients' Perspectives on the Impact of Genital Psoriasis: A Qualitative Study. Dermatol Ther ( Heidelb ). 2017 Dec;7(4):447-461. Perspectives on the Impact of Genital Psoriasis: A Qualitative Study 6

7. Itch (F) [On my arms and legs] it’s just itching, and I scratch it until the itch goes away. But the only place I’ve ever bled was in my genitals because I scratch so much. (F) It’s totally different. It’s like the itch you can’t ever get rid of it. (F) [My other psoriasis] itches, it may be 5 or 7 intermittently, but there’s almost never pain, burning. [Genital psoriasis] itches 24 h a day, a subliminal pain or itch. You can’t scratch it 24 h a day. Pain (M) Pain Other places on my body might itch more, but genital psoriasis is definitely one that hurts the most. (M) The psoriasis I have on my elbows and my knees, there…may be a little discomfort associated. But it’s certainly nothing that affects how I live my life. Whereas the psoriasis has resulted in behavioral changes on the genital side. The pain would be really only in the genital area. (F) This is a different pain. With my psoriasis on the other parts of my body, it’s like some mornings I can’t even get out of bed it hurts so bad. Discomfort or stinging/burning (F) When you walk, sit, stand, you are always using that area. I can’t not notice the discomfort. (F) I don’t really have pain with it. But you can’t dry [that area] out so it stays wet and sore all the time. (F) Stinging/burning The itching is worse on my scalp where I have the thick erythema. The burning is worse in the genital area, it’s like putting a hot match head on your skin. (M) Cracking The other parts of my body all hurt. But they doesn’t ever crack and bleed like my penis and scrotum area…When it cracks it’s exposed to this newer skin so it’s very, very sensitive. Showers are always painful for the first or second day. Representative patient quotations 7 Cather JC, Ryan C, Meeuwis K et. al. Patients' Perspectives on the Impact of Genital Psoriasis: A Qualitative Study. Dermatol Ther ( Heidelb ). 2017 Dec;7(4):447-461. F=female patient, M= male patient

8. Genital Psoriasis was more intense and/or unique compared to extragenital psoriasis Constant intensity of, awareness of, and/or need to manage a symptom in GenPs versus in other locations. Itching was commonly reported for its intensity, and in some cases patients scratched until bleeding occurred. Sensation of pain, particularly that linked to itching. Two patients reported feeling self-conscious that their GenPs might be misidentified as a sexually transmitted disease. Patients attributed the differences with GenPs as due to thinner, more tender skin, more moistness and sweat, greater impact from sweat, increased friction from skin or clothes, and topical treatments not lasting as long. Female Patients Male Patients Cather JC, Ryan C, Meeuwis K et. al. Patients' Perspectives on the Impact of Genital Psoriasis: A Qualitative Study. Dermatol Ther ( Heidelb ). 2017 Dec;7(4):447-461. Perspectives on the Impact of Genital Psoriasis: A Qualitative Study 8

9. Sexual health is diminished in a considerable number of patients with psoriasis and particularly women with genital lesions have on average high levels of sexual distress. Genital lesions alone do not directly hamper sexual function but may rather cause sexual distress in women, who tend to feel less physically attractive because of their skin lesions. 1 “Mean symptom intensity ranged from 2.4 to 5.1, all scores being significantly higher for women compared to men. Severe symptoms were present in up to 43.5% of patients.” 2 Females had a significantly higher frequency of sexual dysfunction than males. Sexual dysfunction in both sexes involved multiple domains of the sexual response cycle, with depression and genital affection by psoriasis being risk factors in both sexes and disease severity being an additional risk factor in females. 3 “The results of the study demonstrated that patients with psoriasis, especially females have distinct sexual dysfunction compared with healthy controls.” 4 1) Meeuwis et al. Quality of life and sexual health in patients with genital psoriasis. Br J Dermatol. 2011;164(6):1247–1255. 2) Meeuwis et al. Patients' experience of psoriasis in the genital area. Dermatology. 2012;224(3):271-6. 3) Alariny et al Psychological and Sexual Consequences of Psoriasis Vulgaris on Patients and Their Partners. J Sex Med. 2019 Dec;16(12):1900-1911. 4) Türel Ermertcan et al Sexual dysfunction in patients with psoriasis. J Dermatol. 2006 Nov;33(11):772-8. The Impact on Sexual Health May be Worse in Women 9

10. The Treatment of Genital Psoriasis 10

11. What type of data do we have (2018)? Types of studies 1 randomized controlled trial (grade 1) 8 open-label studies (grade 4) 16 case reports (grade 5) Treatments and number of patients Topical steroids (n=201) n= 132 low-potency n= 120 moderate-potency n = 15 high-potency Coal tar (n=126) Ixekizumab (n=75) Topical tacrolimus 0.1% (n=40) Vitamin D preparations*(n=40) Antifungal medication (n=3) Topical cyclosporine (n=3) Methotrexate (n=2) Oral dapsone (n=2) 11 * Either by itself of in combination with steroids Beck KM et al. Treatment of Genital Psoriasis: A Systematic Review.  Dermatol Ther ( Heidelb ) . 2018;8(4):509-525.

12. Study Study design Disease site Cohort (M/F) Successful Unsuccessful Notes Bisonette 2008 Open-label, case series Penis, scrotum 12 M 0.1% tacrolimus twice daily Mean genital PASI decreased from 15.8 to 1.2 after 8 weeks Fisher, 2010 Open-label, case series Vulva 8 F TCS 2% LPC, topical calcipotriol Resolution of vulvitis Kapila, 2012 Open-label, case series Vulva 145 F Methylprednisolone aceponate 0.1% (n=110) 2% LPC (n=118) hydrocortisone 1% (n=94) calcipotriol 0.05% (n=10) betamethasone dipropionate 0.05% (n= 7) Betamethasone dipropionate 0.05% + calcioptriol 0.05% (n=4) UVB phototherapy (n=3) Methylprednisolone aceponate 0.1% (n=7) 2% LPC (n=5) hydrocortisone 1% (n=6) 93.8% responded to topical treatment Martin Ezquerra , 2006 Open-label, case series Intertriginous folds 8 M/7 F 0.1% tacrolimus twice daily Improvement as early as day 15, mean total score from 6.88 to 0.37 after 60 days Meeuwis , 2015 Open-label, case series Genitalia 25 M/ 17 F Low-potency corticosteroid cream with Vit D analog (n=18) and without (n=16) moderate-potency corticosteroid cream (n=5) daily tacrolimus with low potency corticosteroid cream (n=2) alternating mild and higher potency corticosteroid cream (n=1) Significant improvement in PASI, IA, SUM, DLQI, FSDS, sQoL -M Rallis, 2005 Open-label, case series Glans, penis, scrotum 7 M 0.1% Tacrolimus twice daily for 10 days then every 7 days thereafter Complete clearance after 3 weeks, 43% still clear at 12 weeks Adapted from (single cases excluded) Beck KM et al. Treatment of Genital Psoriasis: A Systematic Review.  Dermatol Ther ( Heidelb ) . 2018;8(4):509-525. Adapted from: Treatment of Genital Psoriasis: A Systematic Review 12

13. Study Study design Disease site Cohort (M/F) Successful Unsuccessful Notes Ryan, 2018 Randomized, placebocontrolled phase III clinical trial Genitalia 56 M/ 19 F Ixekizumab 160 mg at week 0, then 80 mg every 2 weeks thereafter Significant improvement in genital psoriasis symptoms compared with placebo as measured by sPGA-G 0/1 (74% vs. 8%), GenPS -SFQ item 2 score 0/1 (78% vs. 21%), and C 3 point reduction in genital itch NRS (60% vs. 8%) “Various therapies have been shown to be effective for genital psoriasis in case reports and case series, but high-quality evidence in the form of randomized controlled trials remains inadequate for genital psoriasis treatments.” Adapted from Beck KM et al. Treatment of Genital Psoriasis: A Systematic Review.  Dermatol Ther ( Heidelb ) . 2018;8(4):509-525. Adapted from: Treatment of Genital Psoriasis: A Systematic Review 13

14. Study characteristics Treatments and outcomes Source First author, year Study design Type of psoriasis Cohort, No. patients (M/F, age group) Site Therapy 1 Therapy 2 Conclusion/remarks Amichai , 2004 (62) Case report Plaque 1 (1/0, C) Glans penis 1% pimecrolimus cream, 3 weeks, topical Treatment was effective Jemec & Baadsgaard, 1993 (63) Open label Plaque 3 (3/0, A) Glans penis & inner fold prepuce (=mucosal skin) Topical cyclosporine (100 mg/ml) as a wet dressing, 3 times a day Marked local improvement within 4 weeks; no side effects Weinrauch & Katz, 1986 (42) Case report Plaque 1 (0/1, A) Labium majus Betamethasone-17-valerate ointment, 3 times a day Lesions disappeared in several days Andersen & Thomsen, 1971 (54) Case series Plaque 67 (35/32, C) Napkin area Corticosteroid ointment: only effective in three patients Coal-tar: effective in the remaining 64 patients Zinc paste and salicylic acid ointment were ineffective Watanabe et al., 2002 (64) Case report Plaque 1 (1/0, C) Napkin area 0.2% ketoconazole cream Lesions gradually resolved Singh & Thappa , 2008 (53) Case report Pustular 1 (1/0, A) Glans Dapsone, 100 mg daily Lesions subsided completely in 4 weeks Quan & Ruben, 1996 (52) Case report Pustular 1 (1/0, A) Glans penis and distal penile shaft 1% hydrocortisone and 2% coal-tar: little improvement Oral itraconazole 200 mg, twice daily for 6 weeks: some improvement Itraconazole was directed towards possible Candida colonization Table III. Case reports/series on treatment of genital psoriasis M: male; F: female; LoE : level of evidence; C: children; A: adults. Meeuwis KA et al. Genital psoriasis: A systematic literature review on this hidden skin disease. Acta Derm Venereol . 2011 Jan;91(1):5-11. Adapted from: Genital psoriasis: A systematic literature review on this hidden skin disease (2011) 14

15. Recommendations from Treatment of Genital Psoriasis: A Systematic Review.  Low-to-mid-potency topical corticosteroids are recommended as the first-line treatment for genital psoriasis (grade of recommendation: D) and are commonly reported in the literature to be a critical component of treatment for these lesions. Use with caution due to thin skin and constant occlusion. Mild topical steroids may not be potent enough and may be used with second-line topical therapies. “Moderate-to-high-potency corticosteroids have been used effectively in adults and children with genital psoriasis, both as monotherapy and in combination with other topical agents, without reports of significant adverse effects. However, there was a lack of reporting on adverse effects from topical corticosteroids in studies included our analysis; therefore, there is not enough evidence to determine whether there were no side effects with these therapies or if they simply were not mentioned” 15 Beck KM et al. Treatment of Genital Psoriasis: A Systematic Review.  Dermatol Ther ( Heidelb ) . 2018;8(4):509-525.

16. Recommendations from Treatment of Genital Psoriasis: A Systematic Review.  The data in this analysis do not show superior efficacy for nonsteroidal topical treatments compared with topical corticosteroids. Topical calcineurin inhibitors did improve genital psoriasis in several patients and were fairly well tolerated. Mild burning or pruritus can be associated with using these treatments in the sensitive groin region, but these symptoms are often manageable and limited in duration Topical coal tar preparations demonstrate efficacy in both adults and children with genital lesions and are not associated with significant adverse effects. Vitamin D analogs are sometimes recommended for patients with general psoriasis (grade of recommendation: D). However, these nonsteroidal topical therapies may increase the risk for lymphoma, be more irritating, and be more costly than topical corticosteroids Topical calcineurin inhibitors, coal tar preparations, and vitamin D analogs may thus be used as second-line therapies for psoriasis lesions in the genital area (grade of recommendation: C) 16 Beck KM et al. Treatment of Genital Psoriasis: A Systematic Review.  Dermatol Ther ( Heidelb ) . 2018;8(4):509-525.

17. Recommendations from Treatment of Genital Psoriasis: A Systematic Review.  Systemic therapies such as dapsone and methotrexate can work well for patients with genital lesions and should be considered for patients with debilitating quality of life impairment (grade of recommendation: C). Our analysis did not find any evidence on the use of other traditional systemic agents, such as oral cyclosporine, acitretin, or apremilast, specifically for genital psoriasis. Although numerous effective biologics are available for the treatment of psoriasis, there is only one published clinical trial result on the efficacy of currently approved biologics specifically for genital psoriasis. 17 Beck KM et al. Treatment of Genital Psoriasis: A Systematic Review.  Dermatol Ther ( Heidelb ) . 2018;8(4):509-525.

18. BIOLOGIC IN THE TREATMENT OF GENITAL PSORIASIS 18

19. In the phase III PHOENIX 1 and 2 trials for ustekinumab DLQI Question #9, impaired sexual function was defined as 'very much' or 'a lot' of sexual difficulties. Results:  At baseline, impaired sexual function was reported by 22.6% (women=27.1%; men=20.8%) and was significantly associated with increased psoriasis severity. At week 12, the proportion of patients with impaired sexual function decreased from 22.4% to 2.7% compared with no change with placebo (P<0.001).  Guenther et. al. Impact of ustekinumab on health-related quality of life and sexual difficulties associated with psoriasis: results from two phase III clinical trials. J Eur Acad Dermatol Venereol . 2011 Jul;25(7):851-7. 19 Phase III results for Ustekinumab Based on DLQI Question #9

20. In order to conduct a trial specific for genital psoriasis a validated measurement of disease severity and impact had to be created. Merola et al. The Static Physician's Global Assessment of Genitalia: A Clinical Outcome Measure for the Severity of Genital Psoriasis. J Drugs Dermatol. 2017 Aug 1;16(8):793-799. 20

21. The sPGA-G evaluates three clinical features of genital psoriatic lesions: erythema, plaque elevation, and scale. While the overall score represents a combination of all three features, it should primarily be determined by the degree of erythema , as erythema is the dominant feature in the majority of cases of genital psoriasis. A score of (0) clear represents the absence of erythema with or with- out residual post-inflammatory hyper- or hypo-pigmentation. The descriptions and associated scores for erythema are: (1) light pink (minimal) (2) pink to light red (mild) (3) definite red (moderate) (4) bright red (severe) (5) extreme, deep red (very severe).  Merola et al. The Static Physician's Global Assessment of Genitalia: A Clinical Outcome Measure for the Severity of Genital Psoriasis. J Drugs Dermatol. 2017 Aug 1;16(8):793-799. 21 The Static Physician's Global Assessment of Genitalia: A Clinical Outcome Measure for the Severity of Genital Psoriasis

22. Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled phase IIIb study of patients with moderate-to-severe genital psoriasis Patient Population Adults with moderate-to-severe genital psoriasis who were candidates for phototherapy and/or systemic therapy. Overall static Physician’s Global Assessment (sPGA) score ≥ 3 PGA of Genitalia (sPGA-G) score ≥ 3 B ody surface area (BSA) involvement of ≥ 1% C onfirmation of plaque psoriasis in a non-genital area. Eligible participants had failed to respond to, or were intolerant of, at least one topical therapy used for treatment of genital psoriasis. Treatment Randomized 1 : 1 to receive placebo (n = 74) or the recommended dosing of ixekizumab (n = 75). Outcomes Primary Endpoint: Percentage of patients achieving 0 or 1 scores on the sPGA-G Secondary: O verall sPGA, GenPs Sexual Frequency Questionnaire ( GenPs -SFQ) item 2, and ≥ 3-point improvement from baseline on the GenPs itch numerical rating scale. 22 Ryan et al IXORA-Q Study Group. Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled phase IIIb study of patients with moderate-to-severe genital psoriasis. Br J Dermatol. 2018 Oct;179(4):844-852.

23. Baseline Demographics ~40% of patients had a BSA<10% 3/4 of the patients were male. 19 female patients were randomized to Ixe at baseline (36 female patients in total) Ryan et al IXORA-Q Study Group. Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled phase IIIb study of patients with moderate-to-severe genital psoriasis. Br J Dermatol. 2018 Oct;179(4):844-852. 23

24. Results:  At week 12, ixekizumab was superior to placebo for sPGA-G 0/1 (73% vs. 8%, P < 0·001) A total of 52 (35%) patients increased dosing frequency from IXE Q4W to IXE Q2W during the open-label treatment period, including 25 (33%) patients initially randomized to IXE. Primary (12 w) sPGA-G 0/1 sPGA-G 0 At least a 2 points improvement of sPGA-G Guenther et al. Ixekizumab Results in Persistent Clinical Improvement in Moderate-to-Severe Genital Psoriasis During a 52 Week, Randomized, Placebo-Controlled, Phase 3 Clinical Trial. Acta Derm Venereol . 2020 Jan 7;100(1): 24 BSA>10 or <10

25. Examples of responses Guenther et al. Ixekizumab Results in Persistent Clinical Improvement in Moderate-to-Severe Genital Psoriasis During a 52 Week, Randomized, Placebo-Controlled, Phase 3 Clinical Trial. Acta Derm Venereol . 2020 Jan 7;100(1): 25

26. Table 1 Clinical characteristics and baseline demographics of the study population Characteristics Patients* n = 78 (%) Male 56 (71.8), Female 22 (28.2) Age, y a 47.9 ± 16.5 BMI (Kg/m2) a 28.8 ± 8.7 Age at onset of psoriasis, y a 32.4 ± 17.6 Duration of psoriasis, y a 16.8 ± 12.9 PASI a 18.5 ± 8.5 sPGA-G score no genital psoriasis (0) 43 (70.5) 1 4 (6.6) 2 2 (3.3) 3 3 (4.9) 4 3 (4.9) 5 6 (9.8) Number of previous treatments a 2.9 ± 2.3 Bio-experienced 37 (47.4) 1 biologic agent 18 (48.6) ≥2 biologic agents 19 (51.4) DLQI a 19.7 ± 6.2 T he static Physician Global Assessment of Genitalia (sPGA-G ) was used (as in the trial with ixekizumab) The effectiveness of brodalumab treatment was evaluated at weeks 4, 12 and 24 Case Serie with Brodalumab Fargnoli et al. BRILLIANT Working Group. Brodalumab for the treatment of moderate-to-severe plaque-type psoriasis: a real-life, retrospective 24-week experience. J Eur Acad Dermatol Venereol . 2021 Mar;35(3):693-700. 26

27. S imilarly, sPGA-G scores of clear or almost clear genital skin (sPGA-G 0/1) were achieved by 72.2% (13 of 18) of patients after 4 weeks of brodalumab treatment; The proportion of responders increased to 88.9% (16 of 18) at week 12 and remained stable until the end of the 24-week study period. No dose-optimization was used The baseline and patient characteristics specifically for these 18 patients were not reported Fargnoli et al. BRILLIANT Working Group. Brodalumab for the treatment of moderate-to-severe plaque-type psoriasis: a real-life, retrospective 24-week experience. J Eur Acad Dermatol Venereol . 2021 Mar;35(3):693-700. Case Serie with Brodalumab 27 N=18

28. Genital Psoriasis & Treatment Guidelines Disease at special sites are increasingly recognised as having a disproportionate negative impact on the quality of life. However, most guidelines are vague and often stops by just suggesting that this should be considered without suggesting exactly how this could be done. This includes Canadian publications (Gulliver 2014, Gladman 2017) that are not giving disease location a prominent role Access to systemic treatment is often limited in patients with a lower BSA involvement and/or a lower PASI score Counter argument from payers can be: Do we know how much the genital disease will improve? Do we know the QoL impact and how much this will improve, PRO used? Trials of biologics only include patients above a certain BSA and PASI score What do we know about the impact in patients with less severe disease? 28

29. Consensus statement and guidelines: Suggested Patient Involvement and PROs in Plaque Psoriasis 29 Consensus statement or guideline Patient Involvement & PROs Puig, 2013, Spanish The patient’s opinion must also be taken into account. Carretero, 2018, Spanish DLQI, pruritus' by VAS Gisondo, 2017, Italy Qol should be considered, DLQI<5, disease location Gisondo, 2021, Italy Include QoL, DLQI ≤ 3, disease location Amatore, 2019, French DLQI, patient satisfaction, shared decision making should be incorporated, disease location Armstrong, 2017 National Psoriasis Foundation Wanted a single criteria for simplicity (BSA<1%). Patients communicated that BSA does not capture location, symptoms, comorbidities, or QoL Grine, 2020, Belgian Itch VAS ≤ 10 mm, No difficult locations , DLQI ≤ 1, Daily functioning VAS ≤ 10 mm, Shared decision making is required Strober, IPC 2019, International Needs to be customized to the patient. i.e. itch, PRO strongly suggested Gulliver, 2014, Canada QoL important and should be considered but established measurements are not practical Gladman, 2017, Canada Include QoL, Patient should be in agreement

30. Gisondi et al. Italian guidelines on the systemic treatments of moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol. 2017 May;31(5):774-790. Carretero et al. From the Spanish Group of Psoriasis. Redefining the therapeutic objective in psoriatic patients candidates for biological therapy. J Dermatolog Treat. 2018 Jun;29(4):334-346. Amatore et al. Psoriasis Research Group of the French Society of Dermatology. French guidelines on the use of systemic treatments for moderate-to-severe psoriasis in adults. J Eur Acad Dermatol Venereol. 2019;33(3): 464–83. Mrowietz et al. Definition of treatment goals for moderate to severe psoriasis: a European consensus. Arch Dermatol Res. 2011 Jan;303(1):1-10. Puig et al. Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology. Spanish evidence-based guidelines on the treatment of psoriasis with biologic agents, 2013. Part 1: on efficacy and choice of treatment. Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology. Actas Dermosifiliogr. 2013 Oct;104(8):694-709. Gisondi et al Treat-to-Target Approach for the Management of Patients with Moderate-to-Severe Plaque Psoriasis: Consensus Recommendations. Dermatol Ther (Heidelb). 2021 Feb;11(1):235-252. Mahil et al. Psoriasis treat to target: defining outcomes in psoriasis using data from a real-world, population-based cohort study (the British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR). Br J Dermatol. 2020 May;182(5):1158-1166. Armstrong et al. From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017 Feb;76(2):290-298. Grine et al. Belgian Psoriasis T2T Specialist Group, Lambert J. A Belgian consensus on the definition of a treat-to-target outcome set in psoriasis management. J Eur Acad Dermatol Venereol. 2020 Apr;34(4):676-684. Strober et al. Clinical Goals and Barriers to Effective Psoriasis Care. Dermatol Ther (Heidelb). 2019 Mar;9(1):5-18. Gulliver et al. Think beyond the Skin: 2014 Canadian Expert Opinion Paper on Treating to Target in Plaque Psoriasis. J Cutan Med Surg. 2015 Jan-Feb;19(1):22-7. Gladman et al. Treating Psoriasis and Psoriatic Arthritis: Position Paper on Applying the Treat-to-target Concept to Canadian Daily Practice. J Rheumatol. 2017 Apr;44(4):519-534. References for previous slide

31. 31 Recent Guidelines from the International Psoriasis Council IPC 1 : Candidates for systemic therapy if they meet one of the following criteria: 1) BSA involvement > 10%; 2) disease involving special areas (face, palms, soles, genitalia, scalp, nails) 3) or failure of topical therapy. 1) Strober, Disease Severity Project Update, IPC - 2020 Virtual Think Tank Meeting Report (psoriasiscouncil.org) https://www.psoriasiscouncil.org/blog/2020-Think-Tank.htm Graph: LeQuang Jo Ann, Meeting Proceedings, Updates in Psoriasis Management 2020—Based on Selected Presentations from Maui Derm 2020, January 25–29, 2020, Maui, Hawaii New Developments in the Treatment of Moderate-to-severe Psoriasis, Based on a presentation by Craig Leonardi, St. Louis, Missouri, JCAD 2020;13(7):S7-S23

32. Due to the physical, emotional, and social burden of GenPs on patients, guidelines for the treatment of psoriasis suggest that even in patients with low body surface area involvement, involvement of genital skin may justify its classification as moderate or severe disease and thus warrant systemic treatment, especially if topical treatments are ineffective 1 . Affected body surface area has historically been used in the clinical setting to evaluate whether patients should be started on systemic treatment, but this paradigm has begun to fall out of favor. Localized psoriasis, such as involvement of the genitals, can significantly impair patients physically, socially, and emotionally, even to the point of debilitating depression. Patients with significant quality of life deficits due to skin disease are recommended to be started on systemic treatment, even without diffuse cutaneous involvement 2 . “Finally, it is worth noting the result reported by Meeuwis et al., according to which only 9% of their patients were satisfied with the attention given by healthcare professionals to their sexual problems, while 43% perceived it as insufficient. Those data emphasize that this type of symptomatology is frequently neglected in medical practice 1 ” 32 1) Cather JC, Ryan C, Meeuwis K et. al. Patients' Perspectives on the Impact of Genital Psoriasis: A Qualitative Study. Dermatol Ther (Heidelb). 2017 Dec;7(4):447-461. 2) Yang EJ, Beck KM, Sanchez IM, Koo J, Liao W. The impact of genital psoriasis on quality of life: a systematic review. Psoriasis (Auckl). 2018;8:41-47. Published 2018 Aug 28. 3) Molina-Leyva A, Jiménez- Moleón JJ, Naranjo- Sintes R, Ruiz- Carrascosa JC. Sexual dysfunction in psoriasis: a systematic review. J Eur Acad Dermatol Venereol . 2015 Apr;29(4):649-55.