Systemic Therapy & Biologicsfor

PSORIASIS

Chang Choong ChorConsultant DermatologistCC Chang Skin Specialist @ Gleneagles Kuala Lumpur

PsoriasisChronic immune mediated multi-system disorderpredominantly affecting skin, nails, joints• relapsing and remitting course• physically and psychologically disabling• treatment is prolonged and challenging

Typical psoriasis skin lesions: Well-circumscribed, erythematous scaly plaques

Genetic and Environmental Factors Trigger Keratinocytes to Release ProinflammatoryCytokines

Psoriasis

Environmental Factors

Genetic Predisposition

Release of pro-inflammatory cytokines

Multiple triggering factors in predisposed

individualsMultiple genetic loci linked to psoriasis

Epidermal stress and inflammation

Proliferation of keratinocytes

Elder JT, et al. JID 2010;130:1213

Chiricozzi A, et al. Int J Mol Sci. 2018, 18, 179

Pathogenesis of psoriasis (2018)

IL-23/IL-17 Axis

Pathogenesis of psoriasis (2018)

Chan TC, et al. Ther Adv Chronic Dis 2018, Vol. 9(5) 111–119

Clinical types of psoriasis• Plaque psoriasis (psoriasis vulgaris)

• Classic (85%, 79%)• Flexural / Intertriginous (0.4%, 0.8%)• Scalp predominant• Palmoplantar (non-pustular) (0.3%, 0.2%)

• Guttate psoriasis (3.2%, 7.2%)

• Erythrodermic psoriasis (1.7%, 0.8%)

• Pustular psoriasis (1.1%, 1.5%)• Localised• Generalised• Pustular psoriasis in pregnancy

Source of data : Malaysian Psoriasis Registry 2007-2015(Percentages are for adults and children respectively)

Malaysian Psoriasis Registry 2007-2015

http://www.acrm.org.my/dermreg/mpr.php

52%

32%

16%

ChildrenN=745

27%

46%

27%

AdultsN=9,352

Malaysian Psoriasis Registry2007 – 2015

BSA <5%

BSA 5-10%

BSA >10%

Malaysian Psoriasis Registry2007 – 2015

Adults (age ≥ 18) Children (age < 18)Male-to-female ratio 1.4 : 1 0.7 : 1Mean age of onset 35 ± 16 10 ± 4Family history of psoriasis 23.1% 21.1%Psoriatic arthropathy 13.7% 1.6%Psoriatic nail disease 58.2% 36.1%Overweight / obese 58.1% 28.1%Topical therapy 94.9% 93.2%Phototherapy 3.2% 1.5%Systemic therapy 18.8% 5.4%

(N=14,516)

22% 6.9%

Psoriasis therapy

Topical Rx Phototherapy Systemic Rx

Topical steroidsVit D3 analoguesCoal TarKeratolyticsDithranol (anthralin)EmollientsTopical retinoid(Tazarotene)

NB-UVBOral PUVABath PUVATopical PUVA308nm excimer laser

MethotrexateAcitretinCyclosporinSulfasalazine (PsA)Leflunomide (PsA)BiologicsApremilastSystemic steroids*

Safe Relatively safe Potential risks*only in no choice situations

Severe plaque psoriasis

Erythrodermic psoriasis

Generalised pustular psoriasis

Psoriatic Arthritis (PsA)

Distal interphalangeal joint arthritis

Symmetrical polyarthritis

Asymmetrical oligoarthritis

Arthritis mutilans

Systemic therapy• Should be considered in patients with

– Moderate and severe plaque psoriasis– Psoriatic arthritis– Erythrodermic psoriasis– Pustular psoriasis

• Patient counselling: indication, options, risks• Pre-treatment assessment• Baseline and regular monitoring

Advances in the Treatment of PsoriasisUS FDA approval of treatments

GoeckermanRegime

Methotrexate

Ustekinumab

Etretinate

Cyclosporine

Calcipotriene

1920 1970 1990 2000 2020

AcitretinPUVAAdalimumab

Infliximab

Etanercept

20101980

Secukinumab

Apremilast

Ixekizumab

Guselkumab

BIOLOGIC ERA

Systemic agentsConventional systemic agents

– Methotrexate (Pso, PsA)– Acitretin (Pso)– Cyclosporin (Pso)– Sulfasalazine (PsA)– Leflunomide (PsA)– Systemic steroids (Pso, PsA)

BiologicsOthers

– Apremilast (Pso, PsA)– Tofacitinib (PsA, Pso)

Factors to considerPatient factors

– Age– Co-morbidities

• CKD, hepatitis, HIV, etc

– Pregnancy– Previous treatment– Financial status

Disease factors– Type of psoriasis– Presence of PsA

Drug factors– Availability– Cost of drug + monitoring– Onset of action– Frequency of dosing– Tolerability– Long term safety– Drug interaction

Assessment of severityPASI

What the doctor seesDLQI

How badly the patient suffers

Psoriasis Area and Severity Index (PASI)

• PASI combines the assessment of the severity of lesions and the area affected in to a single score

Head (includes neck)

4 Body Areas Grading of Psoriatic Plaques

Upper limbs (includes hands)

Trunk (includes axillae and groin)

Lower limbs (includes buttocks)

Composite absolute score: 0–72Treatment response relative to baseline: PASI 75/90/100

Erythema

Induration

Scaling

Body Areas Image modified from Smart Image database grading of psoriatic plaques images from PASI meterImage from: PASI score. http://www.dermnetnz.org/scaly/pasi.htmlFredriksson T, et al. Dermatologica 1978;157:238; Langley RG, et al. JAAD 2004;51:563

Body Surface Area (BSA)

• Measurement of involved BSA is estimated by the patient’s handprint (one full palm and fingers = 1% BSA) – Head and Neck = 10% (10 handprints)

– Upper extremities = 20% (20 handprints)

– Trunk (axillae and groin) = 30% (30 handprints)

– Lower extremities (buttocks) = 40% (40 handprints)

– Total BSA = 100% (100 handprints)

Finlay AY. BJD 2005;152:861

Dermatology Life Quality Index (DLQI)

10 questions covering 6 domains:Symptoms and feelings, daily activities, leisure, work and school, personal relationships, bother with treatmentsResponses from 0 (not affected at all) to 3 (very much affected) Overall score between 030Lower score = higher quality of life

1. Finlay AY, Khan GK. Clin Exp Dermatol 1994;19:210;2. Feldman SR, Krueger GG. ARD 2005;64(Suppl II):ii65

DLQI Band Effect on Patient’s Life

0–1 No effect

2–5 Small effect

6–10 Moderate effect

11–20 Very large effect

21–30 Extremely large effect

Treatment Goals

Methotrexate

• First-line systemic treatment for moderate to severe psoriasis

• Inhibit dihydrofolate reductase• Dose: 7.5 – 20 mg/week PO or IM or SC

ONCE WEEKLY DOSING

• Folic acid supplementation recommended

Methotrexate – adverse effects• Gastrointestinal effects

• Nausea, vomiting, diarrhoea, abd pain, GI ulceration

• Liver toxicity• Elevated liver enzymes• Liver fibrosis

– Risk factors: type 2 DM, obesity, NASH, alcohol, hepatitis B or C

• Bone marrow suppression• Risk factors: renal insufficiency, elderly, dosing error, alcohol, drug

interaction, lack of folate supplementation• Monitoring: LFT, procollagen III aminopeptide, Fibroscan, liver

biopsy

• Others: • Malaise, alopecia, photosensitivity, pneumonitis, lung fibrosis