Treatment of psoriasis

Treatment of Psoriasis

1. Treatment of PSORIASIS Dr. Asaf K Al- Doury

2. The goal is to reach minimal or no skin involvement with a well-tolerated treatment regimen.   The acceptable response for plaque psoriasis after 3 months of treatment: <3% body surface area (BSA) involvement or 75% improvement   The target response after 6 months ≤1% BSA.

3. Psychosocial aspects    Psoriasis is a frustrating disease. be empathetic and spend adequate time with the patient. touch the patient when possible to prove that it is neither repulsive nor contagious. there is no cure for psoriasis. Educate the patient, making it clear that the primary goal is control the disease Psoriasis may cause depression, counseling/treatment with psychoactive medications.

4. Choice of therapy 1. Limited disease managed with topical agents , 2. moderate to severe disease may need phototherapy or systemic therapy. The disease location: psoriasis of the hand, foot, or face is debilitating so need more aggressive treatment. Moderate to severe psoriasis: is 1. involvement of >5-10% BSA, or 2. involvement of the face, palm or sole, or 3. disease that is otherwise disabling. >5% BSA require phototherapy or systemic therapy Widespread pustular disease requires aggressive treatment, ( s.t. hospitalization).

5. Limited disease    Corticosteroids, Emollients, vitamin D analogs (calcipotriene and  calcitriol ), tar, Topical retinoids (tazarotene). Topical tacrolimus or pimecrolimus for facial or intertriginous areas, as corticosteroid sparing agents. Localized phototherapy.   Combinations: Potent topical corticosteroids + calcipotriene,  calcitriol ,  tazarotene, or UVB phototherapy. Calcipotriene + Class I topical corticosteroids for short-term control. Then calcipotriene alone or with potent corticosteroids used (on weekends) for maintenance.

6. Moderate to severe disease 1. retinoids, 2. methotrexate, 3. cyclosporine, 4. apremilast , or 5. biologic immune modifying agents. a. anti-tumor necrosis factor (TNF) agents i. adalimumab , ii. etanercept , iii. infliximab, and iv. certolizumab pegol ; b. the anti-interleukin (IL) i. IL12/IL-23 antibody ustekinumab ii. IL-17 antibodies secukinumab and ixekizumab ; iii. anti-IL-17 receptor antibody brodalumab ; and iv. IL-23/IL-39 antibodies guselkumab and tildrakizumab .

7. Topical Therapy 1. Emollients Petroleum jelly or thick creams. Hydration and emollients are adjuncts to psoriasis treatment. Minimizes the symptoms of itching and tenderness, thus subsequent Koebnerization .

8. Topical Therapy 2. Local Corticosteroids anti-inflammatory, antiproliferative , and immunosuppressive actions The efficacy/potency  of a topical corticosteroid is dependent on: application site, plaque thickness, the vehicle, how well drug molecule activates corticosteroid receptors , compliance.

9. Topical Therapy 2. Local Corticosteroids ●On the scalp or in the external ear canal: potent corticosteroids solution (e.g.,  fluocinonide 0.05% or clobetasol propionate 0.05 %). Clobetasol 0.05% shampoo, foam, or spray. Afro hair may prefer ointment vehicle for scalp. ● On the face and intertriginous areas: a low-potency ointment or cream (e.g., over-the-counter hydrocortisone 1% or prescription-strength 2.5 %). ●For thick plaques on extensor surfaces: potent preparations (e.g.,  betamethasone 0.05% or clobetasol propionate 0.05%) are often required.

10. Topical Therapy 2. Local Corticosteroids Twice daily application of topical corticosteroids  rapid decrease in inflammation can be continued as long as the patient has thick active lesions Improvement: then reduce frequency recur quickly: then applied intermittently (such as on weekends only ) Add topical noncorticosteroid to avoid long term daily application

11. Topical Therapy 2. Local Corticosteroids S/E: Dermal atrophy tachyphylaxis relapse adrenal suppression

12. Topical Therapy 2. Local Corticosteroids Brand name Generic name CLASS 1— Superpotent Clobex Lotion/Spray/Shampoo, 0.05% Clobetasol propionate Cordran Tape, 0.05% Flurandrenolide Cormax Cream/Solution, 0.05% Clobetasol propionate Diprolene Ointment, 0.05% Betamethasone dipropionate Olux E Foam, 0.05% Clobetasol propionate Olux Foam, 0.05% Clobetasol propionate Psorcon Ointment, 0.05% Diflorasone diacetate Psorcon E Ointment, 0.05% Diflorasone diacetate Temovate Cream/Ointment/Solution, 0.05% Clobetasol propionate Topicort Topical Spray, 0.25% Desoximetasone Ultravate Cream/Ointment, 0.05% Halobetasol propionate Ultravate Lotion, 0.05% Halobetasol propionate Vanos Cream, 0.1% Fluocinonide

13. Topical Therapy 2. Local Corticosteroids CLASS 2—Potent Diprolene Cream AF, 0.05% Betamethasone dipropionate Elocon Ointment, 0.1% Mometasone furoate Florone Ointment, 0.05% Diflorasone diacetate Halog Ointment/Cream, 0.1% Halcinonide Lidex Cream/Gel/Ointment, 0.05% Fluocinonide Psorcon Cream, 0.05% Diflorasone diacetate Topicort Cream/Ointment, 0.25% Desoximetasone Topicort Gel, 0.05% Desoximetasone

14. Topical Therapy 2. Local Corticosteroids CLASS 3—Upper Mid-Strength Cutivate Ointment, 0.005% Fluticasone propionate Lidex-E Cream, 0.05% Fluocinonide Luxiq Foam, 0.12% Betamethasone valerate CLASS 4—Mid-Strength Cordran Ointment, 0.05% Flurandrenolide Elocon Cream, 0.1% Mometasone furoate Kenalog Cream/Spray, 0.1% Triamcinolone acetonide Synalar Ointment, 0.03% Fluocinolone acetonide Topicort LP Cream, 0.05% Desoximetasone Topicort LP Ointment, 0.05% Desoximetasone Westcort Ointment, 0.2% Hydrocortisone valerate

15. Topical Therapy 2. Local Corticosteroids CLASS 5—Lower Mid-Strength Capex Shampoo, 0.01% Fluocinolone acetonide Cordran Cream/Lotion/Tape, 0.05% Flurandrenolide Cutivate Cream/Lotion, 0.05% Fluticasone propionate DermAtop Cream, 0.1% Prednicarbate DesOwen Lotion, 0.05% Desonide Locoid Cream/Lotion/Ointment/Solution, 0.1% Hydrocortisone Pandel Cream, 0.1% Hydrocortisone Synalar Cream, 0.03%/0.01% Fluocinolone acetonide Westcort Cream, 0.2% Hydrocortisone valerate

16. Topical Therapy 2. Local Corticosteroids CLASS 6—Mild Aclovate Cream/Ointment, 0.05% Alclometasone dipropionate Derma-Smoothe/FS Oil, 0.01% Fluocinolone acetonide Desonate Gel, 0.05% Desonide Synalar Cream/Solution, 0.01% Fluocinolone acetonide Verdeso Foam, 0.05% Desonide CLASS 7—Least Potent Cetacort Lotion, 0.5%/1% Hydrocortisone Cortaid Cream/Spray/Ointment Hydrocortisone Hytone Cream/Lotion, 1%/2.5% Hydrocortisone Micort-HC Cream, 2%/2.5% Hydrocortisone Nutracort Lotion, 1%/2.5% Hydrocortisone Synacort Cream, 1%/2.5% Hydrocortisone

17. Topical Therapy 3. Vitamin D analogues Calcipotriol , Calcitriol , and Tacalcitol for mild-moderate psoriasis, <40% of skin MOA: keratinocyte Vit. D receptor  (1)↓proliferation, (2) inhibit polyamines synthesis Reduce scale and thickness 2 daily doses. If irritating add moderate steroid in the morning <100g/wk. Not >1y course. Not used on face or <6y of Age Calcitriol less irritant. Tacalcitol Single night dose Disadvantage: expensive

18. Topical Therapy 3 . Vitamin D analogues Calcipotriol is as effective as a potent steroid Applied twice daily when used as monotherapy Calcipotriene + superpotent corticosteroids (each once daily at different times of day)  increased clinical response and tolerance compared with either agent used alone Skin irritation is the main adverse effect risk of hypercalcemia is low when the drug is used appropriately

19. Topical Therapy 3 . Vitamin D analogues Calcitriol Also inhibits T cell proliferation and other inflammatory mediators As effective as calcipotriol but less irritant in sensitive skin randomized trial of 75 patients compared treatment with calcitriol 3  µg/g  ointment to calcipotriene 50 µ g/g  ointment for mild to moderate psoriasis on facial, hairline, retroauricular , and flexural areas. Perilesional erythema, perilesional edema, and stinging or burning sensations were significantly lower in the areas treated with calcitriol

20. Topical Therapy 4. Coal Tar MOA: (1)Inhibit DNA synthesis , (2) photosensitizes skin, (3) antiinflammatory , (4) antiproliferative . the lesser refined the more messy/smelly but more effective Adjunct to topical corticosteroids Prescribed as shampoos , creams, lotions, ointments, oils, solution and a foam. 2% or 3% crude coal tar in triamcinolone cream 0.1% applied twice daily to individual plaques Or 4-10 % ( liquor carbonis detergens, a tar distillate) in triamcinolone cream or ointment, used similarly. A preparation of 1% tar in a fatty-acid based lotion may be superior to conventional 5% tar products (as effective as calcipotriene) Tar shampoo should be left in place for 5-10 minutes before rinsing.

21. Topical Therapy 4. Coal Tar

22. Topical Therapy 5. Local Retinoids Tazarotene Retinoic acid receptor (RAR)  (1)↓proliferation, (2) normalize differentiation, (3) ↓dermal inflammatory cell infiltrate For stable chronic plague ≥20% Used single evening dose for 12wk 0.1-0.05% gel used. If irritation reduce the strength, dose, or add steroid Not used <18y nor for pregnant 20 minute application followed by washing: less irritating, and have similar efficacy Irritation is reduced by concomitant treatment with a topical corticosteroid

23. Topical Therapy 5. Local Retinoids Tazarotene

24. Topical Therapy 6. Calcineurin inhibitor Tacrolimus (0.1%), pimecrolimus (1%) Weak, used for face, genitals, and intertriginous areas Well tolerated but less effective compared with local steroids

25. Topical Therapy 7. Dithranol (anthralin) MOA: (1)Inhibit DNA synthesis , (2) O 2 free radical formation Start with weak 0.1% then step up weekly interval up to 2% Apply ≤30min daily 5days a week for a 1 month Not for face, closed skin, avoid eye contact Petrolatum or zinc oxide may be applied to uninvolved surrounding skin as a protectant prior to application Side effect: skin irritation, permanent red-brown stains clothes and temporary purple staini ng of skin  reduction of patient adherence . Anthralin is less effective than topical vitamin D or potent topical corticosteroid therapy

26. Topical Therapy 7. Dithranol (anthralin)

27. Topical Therapy 8. Salicylic Acid MOA: (1) enhance penetration , (2) antiinflammatory 3-6% for first 2 days of course of treatment

28. Phototherapy beneficial for the control of psoriatic skin lesions MOA: anti-proliferative and anti-inflammatory effects Modalities : UVB ( 290 to 320 nm) for extensive disease, alone or in combination with topical tar. 3/week NB-UVB (311 nm) is an alternative and more effective than BBUVB PUVA : oral or bath psoralen followed by UVA ( 320 to 400 nm ). penetrates deeper into the dermis, and does not burn the skin compared with UVB. Methoxypsoralen ingested then UVA exposed within 2 hours. 3/week in increasing doses until remission, then 1-2/ wk as a maintenance dose psoralen bath soaked for 15-30 minutes prior to UVA exposure No significant difference in efficacy between PUVA and bath

29. Phototherapy post treatment photoprotection (e.g., hat, sunscreen, goggles ) to prevent damage to skin and eyes Gentle removal of plaques by bathing does help prior to UV exposure Favorable features of UVB phototherapy over PUVA due to no psoralen prior to treatment and lower risk of UVB. Home phototherapy narrowband UVB administered via home units was as safe and effective as office-based treatments equipped with electronic controls that allow only a prescribed number of treatments. Less costly

30. Phototherapy Excimer laser   308 nm excimer laser  considerably higher doses results in faster responses than conventional phototherapy After <10 treatments, 84% of patients achieved >90% clearance of plaques. (fewer sessions compared with conventional UVB) Side effects: temporary local tanning, erythema, and blistering Malignancy risk   PUVA increased risk of nonmelanoma skin cancer and melanoma . Contraindicated in history of melanoma or extensive nonmelanoma skin cancer .

31. Phototherapy Folate deficiency   exposure of plasma to UVA led to a 30-50% decrease in the serum folate level within 60 minutes (only in vitro ) Saltwater baths   Exposure to natural sunlight improves psoriasis. Bathing in sea water in combination with sun exposure (climatotherapy) has also been used as a therapy, use of salt water baths with artificial UV ( balneophototherapy ).

32. Phototherapy Saltwater baths   no difference was found between saltwater and tap-water baths, and bath PUVA was superior to UVB after a saltwater bath SE of POVA: (short term) painful erythema, itch, nausea ( long term) skin ageing, CA (>1000J / 250 dose), cataract climatotherapy

33. Phototherapy Saltwater baths   balneophototherapy

34. Systemic Therapy Methotrexate   folic acid  antagonist For moderate to severe cases, for psoriatic arthritis and psoriatic nail Antiproliferative , immunosuppressive against active T cells administered in an intermittent low-dose regimen (once weekly). oral, iv, im , or sc ; the usual dose is 7.5-25 mg /week methotrexate can be used for long-term therapy . {After 16 weeks methotrexate treatment, 41% patients achieved 75% improvement} SE: Stomatitis: prevented by concomitant folic acid 1mg/day pulmonary toxicity, hepatic toxicity: require monitoring bone marrow suppression

35. Systemic Therapy Methotrexate   Risk factors for hepatotoxicity from methotrexate  include: ●alcoholic ●Persistent abnormal liver chemistry ●chronic hepatitis B or C ●Family history of inherited liver disease ( eg , hemochromatosis) ●Diabetes mellitus ●Obesity ●hepatotoxic drugs ●Absence of folate supplementation ●Hyperlipidemia

36. Systemic Therapy Methotrexate   No risk of hepatotoxicity  liver chemistries drawn every 1-3months. Once patients have reached this dose, options include: proceeding with a liver biopsy, continuing to monitor without a liv er biopsy, or discontinuing methotrexate therap y .  

37. Systemic Therapy Methotrexate   For patients discontinue therapy within the first two to six months, perform the biopsy soon after. For patients who continue methotrexate, liver biopsies should be considered after every 1-1.5 g of cumulative methotrexate. patients reached this dose, options include: proceeding with a liver biopsy, discontinuing methotrexate, or consulting with a hepatologist for further evaluation.

38. Systemic Therapy Retinoids    vitamin A derivatives For severe psoriasis, (pustular and erythrodermic) or HIV associated acitretin dose: 25 mg every other day to 50 mg daily can be used in combination with UVB or PUVA therapy Monitoring for hypertriglyceridemia and hepatotoxicity SE: cheilitis, alopecia, and teratogenicity (prevent pregnancy for   3y  after discontinuing the drug)

39. Systemic Therapy Cyclosporine      calcineurin inhibitor The T cell suppressor  For severe psoriasis Dose: 3 to 5 mg/kg per day orally SE: renal toxicity and hypertension

40. Systemic Therapy Apremilast        phosphodiesterase 4 inhibitor For moderate to severe, and for P. arthritis Costly, {33% reach 75% improvement} Dose: schedule 10mg/day raising 10mg everyday till 30mg x2 In renal impairment half of the dose is to be given in the morning SE: diarrhea, nausea, upper respiratory infection, headache, weight loss, depression, and suicidal thoughts

41. Systemic Therapy Apremilast       

42. Systemic Therapy - Biologic agents   TNF-alpha inhibitor   Etanercept         For adults with psoriatic arthritis and for patients age ≥4years with chronic moderate to severe plaque psoriasis Dose : s/c 50 mg 2/ wk for 1st 3 months then 50 mg weekly maintenance (pediatric: 0.8 mg/kg/ wk ) max 50mg/ week { 49% reach 75% clearance after 12wk} Formation of anti- etanercept Ab in 0 -18% of patients (not lower the efficacy of the drug)

43. Systemic Therapy - Biologic agents   TNF-alpha inhibitor   Etanercept        

44. Systemic Therapy - Biologic agents   TNF-alpha inhibitor   Infliximab           For moderate to severe plaque psoriasis, well tolerated onset of action is faster than other biologic drugs Dose: i.v 5 mg/kg at weeks 0, 2, and 6, then every 8 weeks thereafter. {infliximab 5  mg/kg given at weeks 0, 2, 6, 14, and 2 compared with methotrexate   15- 20mg/ week for moderate to severe psoriasis; found patients treated with infliximab exhibited greater improvement ( 78% versus 42% achieved 75% improvement in the PASI score by week 16 )} Anti-infliximab antibodies have been reported to occur in 5 to 44 percent of patients who receive infliximab for psoriasis  loss of response

45. Systemic Therapy - Biologic agents   TNF-alpha inhibitor   Adalimumab            for rheumatoid arthritis and psoriatic arthritis Dose: S/C 80mg then 40mg fortnightly {40 mg fortnightly, 40 mg weekly, After 12 weeks , achieved 75% improvement in the PASI score 53% and 80% respectively} Ab formed in 6-50% of patients and may reduce the response to therapy

46. Systemic Therapy - Biologic agents   TNF-alpha inhibitor   Certolizumab pegol              pegylated humanized antibody Fab fragment with specificity for TNF- α . for moderate to severe psoriasis, and psoriatic arthritis. Dose: 400 mg fortnightly minimal transfer across the placenta does not bind the neonatal Fc receptor because it lacks the IgG Fc . Response rate: 75-80% reach 75% improvement after 16wks SE: nasopharyngitis and upper respiratory infection .

47. Systemic Therapy - Biologic agents   anti-interleukin   Ustekinumab              Anti-IL-12 and IL-23 For moderate to severe psoriasis and psoriatic arthritis Dose: ≤ 100 kg: 45 mg given at weeks 0, 4, and then every 12 weeks. >100Kg: 90 mg in the same regimen. Improvement: 66% reach 75% PASI after 12weeks well tolerated Anti- ustekinumab Ab occur in 4-6% of patients, but no prove for affecting its efficacy.

48. Systemic Therapy - Biologic agents   anti-interleukin   Secukinumab              Anti-IL-17a monoclonal antibody For moderate to severe plaque psoriasis Dose : s/c 300mg/weekly at weeks 0, 1, 2, 3, and 4 then 300mg/month {82% got 75% improvement after 12 weeks}

49. Systemic Therapy - Biologic agents   anti-interleukin   Ixekizumab              Anti-IL-17a monoclonal antibody For moderate to severe plaque psoriasis, and psoriatic arthritis Dose : 160 mg at week 0, then 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg /month {89% got 75% improvement after 12 weeks} SE : transient neutropenia (12%), candidal infection (3%), and inflammatory bowel disease (<1%)

50. Systemic Therapy - Biologic agents   anti-interleukin   Brodalumab              Anti-IL-17a monoclonal antibody For moderate to severe plaque psoriasis Dose : 210 mg at weeks 0, 1, and 2 and then every two weeks {86% got 75% improvement after 12 weeks 44% got PASI 100% compared with 22% for ustekinumab after 12 wks } SE : suicidal ideation , Candida infections, and neutroppenia

51. Systemic Therapy - Biologic agents   anti-interleukin   Guselkumab              immunoglobulin G1 ( IgG1 λ ) lambda monoclonal Ab: binds to p19 subunit of IL-23. IL-39 Effective against moderate to severe and psoriatic arthritis Dose : 100 mg at weeks 0, 4, and then every 2 months {90% PASI after 16 weeks of treatment} SE : Upper respiratory tract infections, tinea and herpes simplex virus infections, arthralgia, diarrhea, and gastroenteritis

52. Systemic Therapy - Biologic agents   anti-interleukin   Tildrakizumab              immunoglobulin G1 (IgG1 κ ) kappa monoclonal Ab: binds to p19 subunit of IL-23 . Effective against moderate to severe psoriasis Dose : s/c 100 mg at weeks 0 and 4 and then every 3 months {64% reach PASI 75 after 12 weeks of treatment} SE : Upper respiratory tract infections, tinea and herpes simplex virus infections, arthralgia, diarrhea, and gastroenteritis

53. Systemic Therapy - Biologic agents   Other immunosuppressive agents                Hydroxyurea, 6-thioguanine , and Azathioprine, when other systemic modalities cannot be used,

54. Systemic Therapy - Biologic agents   Other immunosuppressive agents   Tacrolimus, (requires larger studies). Daclizumab , (used for prevention of renal transplant rejection), Paclitaxel ( cancer chemotherapeutic drug) under investigation for use in severe psoriasis. Abatacept , a drug used for psoriatic arthritis Fumaric acid esters, reduction of psoriasis severity

55. Systemic Therapy - Biologic agents   Tonsillectomy   improvement in psoriasis after tonsillectomy especially guttate psoriasis Relapse after tonsillectomy is also possible . Small molecules Examples for the treatment of psoriasis include molecules that block Janus kinases (JAK ), lipids, and a protein kinase C inhibitor. Oral tofacitinib , a small molecule JAK inhibitor has demonstrated efficacy for moderate to severe plaque psoriasis.

56. Systemic Therapy - Biologic agents   Small molecules Baricitinib , oral reversible inhibitor of JAK1/JAK2 tyrosine kinases, with daily doses of 2 , 4, 8, or 10 mg. Ponesimod , modulate the sphingosine 1-phosphate receptor 1 (S1PR1), a receptor involved in the movement of lymphocytes from secondary lymphoid tissues into the circulation, may be an additional effective method to treat psoriasis.

57. Thank you