Psoriasis

Megan D. Pendley, RPh, PharmD

PPS 946
Spring 2015

Lecture Objectives

• Describe the etiology, exacerbating factors, and pathophysiology of psoriasis

• Describe the clinical presentation of psoriasis
• Discuss the pharmacology, side effects, drug interactions, and proper dosing of
commonly used medications for psoriasis
• Given a patient case, select an appropriate treatment regimen, monitoring
parameters and patient related consultation recommendations considering the
patient's diagnosis and unique characteristics
• Assess a patient’s pharmacotherapeutic regimen for safety and efficacy using
clinical signs, symptoms and laboratory data
• Counsel patients on non-pharmacologic modalities to treat psoriasis

Definition of disease:
 Genetic, systemic, chronic inflammatory disorder which can be altered by environmental factors
 May be associated with other inflammatory disorders such as psoriatic arthritis (PsA),
inflammatory bowel disease (IBD), and coronary artery disease (CAD)
 Non-contagious skin disorder characterized by recurrent exacerbations and remissions of
thickened, erythematous, and scaling patches, papules, and plaques that are often pruritic.

Epidemiology/Etiology:
 Multisystem disease with predominantly skin and joint manifestations affecting about 2-3% of
American population
 Other conditions that can be associated with psoriasis &/or psoriatic arthritis (PsA) include
autoimmune diseases such as IBD, components of the metabolic syndrome such as diabetes,
cardiovascular disease, and lymphoma
 Occurs in all racial groups but most prevalent in Caucasians
 Equally common in males and females; most commonly peaks between 20-30 years of age and
smaller peak between 50-60 years of age
 Significant physical and emotional adverse impact
 Genetic predisposition – most people with psoriasis have at least one immediate relative with the
disorder

Pathophysiology:
 Complex genetic disease of dysregulated inflammation
 At least 8 chromosomal loci have been identified as contributing to the development of psoriasis
 Environmental factors also play a key role (see trigger factors below)
 Immune mediated mechanisms more involved than previously recognized, in which T-
lymphocytes play a key role
 Overall, two major mechanisms:
 o Hyperproliferation and abnormal differentiation of the epidermis
o Immune mediated mechanisms
 T-cell activation occurs→ T-cells migrate from lymph nodes and circulation into
the skin→ T-cells secrete various cytokines that induce the pathologic changes
seen in psoriasis
 Important cytokines: IFN –α,β,γ, IL-2, TNF-α, IL-8

Trigger Factors &/or Behaviors contributing to psoriasis:

 Cold weather
 Stress
 Obesity
 Alcohol and smoking
 Infections
 Lesions tend to develop at repetitive sites of injury (chronic rubbing, venipuncture, mechanical
pressure, etc), known as Koebner phenomenon
 Medications:
o Lithium Carbonate
o Beta blockers
o Antimalarials
o NSAIDs
o ACE Inhibitors
o Tetracyclines & Interferons

Clinical Presentation:
 Major manifestation of psoriasis is chronic inflammation of the skin
 Characterized by disfiguring, scaling, and erythematous plaques that may be painful or often
severely pruritic and may cause significant QoL issues
 Classic lesions are characterized by sharply demarcated, erythematous papules and plaques often
covered with silvery-white scales
 Initial lesions are usually small papules that enlarge over time and coalesce into plaques
 If the covering scale is removed, a salmon-pink to erythematous lesion is exposed, usually with
punctuate bleeding known as Auspitz sign
 About 80% of patients have mild to moderate disease; 20% have moderate to severe disease
 Common sites of involvement are:
o scalp
o trunk
o back
o elbows & knees
o nails
 Psoriasis phenotypes
o Plaque psoriasis:
 Most common form, affecting about 80-90% of patients
 Vast majority of clinical trials have been performed on this type
 Plaques are erythematous with well-defined, sharp margins and raised silvery
scale is present
 Plaques are usually 1-10 cm, are round to oval in shape, symmetrically
distributed, and most often located on the scalp, trunk, buttocks, and limbs with a
predilection for EXTENSOR surfaces (such as elbows and knees)
 o Guttate psoriasis:
 “Dew-drop-like” lesions that usually occur in children or young adults
 Lesions occur abruptly, are very small (1-10mm) and primarily involve the trunk
and proximal extremities
 Lesions are typically salmon-pink papules, usually with a fine scale
 Occurs in < 2% of pts with psoriasis
 There is a strong association between a recent URI with group A beta-hemolytic
strep infection, which precedes the onset of guttate psoriasis (esp in younger pts)
by 2-3 weeks
 The sudden appearance of papular lesions may be either the first manifestation of
psoriasis in a previously unaffected person or an acute exacerbation of long-
standing plaque psoriasis
o Pustular Psoriasis:
 All forms of psoriasis may contain neutrophils in the stratum corneum. When
collections of neutrophils are large enough to be apparent clinically, it is termed
“pustular psoriasis.”
 Can be localized or generalized
 The acute generalized form is very rare but severe, widespread, and life-
threatening. Onset is acute with widespread erythema, scaling, and sheets of
superficial pustules with erosions (most severe form)
 Less severe form presents with multiple localized pustules primarily on palms
and soles with painful fissuring
o Inverse Psoriasis:
 Involves intertriginous areas; i.e. skin folds (inguinal, axillary, perineal, genital,
intergluteal, inframammary regions)
 Because of the moist nature of these areas, the lesions tend to be erythematous
plaques with minimal scale
 Frequently misdiagnosed as a fungal infection
o Erythrodermic Psoriasis:
 Can develop gradually from chronic plaque disease or acutely with little
preceding psoriasis
 Generalized erythema from head to toe (nearly covers the entire BSA) with
varying degrees of scaling
 Altered thermoregulatory properties of erythrodermic skin may lead to chills and
hypothermia, and fluid loss may lead to dehydration. Fever and malaise are
common.
 High risk of infections, sepsis, electrolyte imbalances
 Most often requires inpatient management
o Nail Psoriasis:
 Most commonly affects fingernails
 Few-multiple tiny pits scattered over nail plate (nail pitting) and a yellow-tan or
brown color to the nail (“oil drop sign”), onycholysis, and subungual
hyperkeratosis
 Up to 90% of patients with psoriatic arthritis have nail changes
 Very commonly confused with onychomycosis

Comorbidities:
 Autoimmune diseases
 o Crohn’s Disease and ulcerative colitis
o Possible link btw MS and psoriasis
 Cardiovascular disease
o Increased risk in pts with psoriasis b/c psoriatic pts tend to be overweight, have an
increased incidence of DM, HTN, and have an atherogenic lipoprotein profile at the onset
of psoriasis with significantly higher very-low density lipoprotein cholesterol levels and
high-density lipoprotein levels
o Psoriasis pts have a higher incidence of MI even after correcting for all heart disease risk
factors (the thought is that the chronic inflammatory process of psoriasis plays a role in
the promotion of CHD)
 Metabolic Syndrome (the combination of obesity, impaired glucose regulation,
hypertrigylceridemia, reduced HDL and HTN)
 Lymphoma, melanoma, and nonmelanoma skin cancer –
o This is very controversial!
 Depression/suicide
 Psychologic and emotional burden
o Not always related to extent of skin disease
o Include: poor self-esteem, sexual dysfunction, anxiety, and depression mentioned above

Severity Classification and Pretreatment Considerations:

 PASI= Psoriasis Area and Severity Index – is a measure of overall psoriasis severity and
coverage, and serves as a uniform method to determine the amount of body surface area affected,
along with the degree of erythema, induration, and scaling
o Commonly used in clinical trials to assess baseline psoriasis severity and degree of drug
efficacy at reducing disease severity, but not routinely used in clinical practice
o Goals of therapy: PASI 50 (which represents a 50% decrease in severity from baseline)-
which is considered a clinically relevant end point when assessing efficacy of treatment.
o The newest class of agents, the biologics, were required to demonstrate a PASI 75
decrease for approval by the FDA
o PASI is considered less sensitive in patients with lower BSA (< 10%) involvement

 In clinical practice, the physician generally uses subjective qualitative assessment of severity of a
patient’s psoriasis by combining objective assessment of the BSA involvement, disease location,
thickness, and symptoms, presence or absence of psoriatic arthritis with the subjective
assessment of the physical, financial, and emotional impact of the disease on the patient’s life

 Mild: < 5% BSA involvement

 Moderate: > 5% but < 10% BSA involvement
 Severe: > 10% BSA involvement; or involvement of hands, feet, genitals, facial region or in
which the disease interferes significantly with daily life

Pharmacologic Treatment: General Principles

 Treatment is based on the extent and site of disease involvement, the patient’s age, patient’s
preferences (cost and convenience) and concurrent disease states
 Must also consider the impact of skin lesions on QoL and how treatment will affect that
  Because of the relatively poor compliance frequently seen with topical therapies, patient
preference is a key aspect of decision making.
 Patients are usually started on safer therapies and progress to more aggressive therapies if
response is inadequate
 Initial treatment decision centers around topical therapy or systemic therapy, in which extent of
disease is the major driving factor
 The location of the disease and the presence of psoriatic arthritis also affects the choice of
therapy. Psoriasis of the hand, foot, or face can be debilitating functionally or socially and may
deserve a more aggressive treatment approach.
 Topical therapy and/or targeted phototherapy is the first choice for mild to moderate disease
(accounts for around 80% of cases)
 For extensive, severe, or disabling plaque psoriasis, systemic therapy may be necessary to control
symptoms.
 Consider biologic agents for moderate to severe disease or for those who receive an insufficient
response to topical or targeted phototherapy, or in those with psoriatic arthritis.

Topical Therapy
Considerations
 Considered the mainstay for those with limited disease (<5% BSA)
 Choice of vehicle will alter medication penetration and relative efficacy
o Ointments increase medication delivery and absorption/activity
 Consider patient preference and limitations with each dosing vehicle
o Hair-bearing areas may be best treated with foams, shampoos, gels, and sprays because
they are less likely to leave a residue on the hair
o Creams would be ideal for daytime application because they are less likely to glisten or
stain clothes; creams also good for face and intertriginous areas
o Consider ointments for nighttime application because they have less cosmetic appeal
 Dosing recommendations using fingertip units (ribbon of cream/ointment from tip of finger to
distal interphalangeal joint)----estimate 2% BSA for each fingertip unit
Emollients — Hydration and emollients are valuable and inexpensive adjuncts to psoriasis treatment.
Keeping psoriatic skin soft and moist minimizes the symptoms of itching and tenderness. Additionally,
maintaining proper skin hydration can help prevent irritation and thus the potential for subsequent
Koebnerization (development of new psoriatic lesions at sites of trauma).
The most effective are ointments such as petroleum jelly or thick creams, especially when applied
immediately after a hydrating bath or shower.

Topical Corticosteroids (see table of agents in Lexi-Comp)

Classified using Stoughton-Cornell classification system (1= ultra potent; 7= least potent)
Steroids act by decreasing inflammation, decreasing proliferation of epidermal cells, and suppressing
immune response affecting gene transcription
a) Safety
a. Skin atrophy—a problem if the patient continues to use it after skin has returned to
normal thickness; once improvement occurs, reduce frequency and apply intermittently to
maintain control
b. Exacerbation of dermatologic infections
c. Possible rebound psoriasis symptoms with abrupt corticosteroid withdrawal
b) Tolerability
 a. Pustular or vesicular lesions
b. Hyperesthesia
c. Telangiectasias and purpura
d. Skin atrophy and striae
c) Efficacy
a. Treatment of choice for patients with mild to moderate psoriatic disease
b. Ultra-high potency agents or ointment based preparations are associated with greater
efficacy, but must consider site of application
d) Preference/Pearls
a. As effective as vitamin D analogs with less skin irritation
b. As use continues, reduce potency or frequency of application to the minimal required for
clinical response
c. May continue to use steroids as long as patient has thick active lesions
d. Limit ultra-high potency topical steroids to 50g/week for up to 2-4 weeks
e) Simplicity/Dosing
a. Once or twice daily local application
b. May be used in conjunction with occlusive therapy to boost efficacy

Topical vitamin D analogs [calcipotriene (Calcitrene®, Dovonex®, Sorilux® and calcitriol

(Vectical®)]
a) Safety
a. Hypercalcemia is a concern if applying >100g/week
b. Photosensitivity and increased risk of UV-induced skin tumors
b) Tolerability
a. Skin irritation---major effect (Calcitriol induces less skin irritation than calcipotriene and
is better for use in sensitive areas such as skin folds)
c) Efficacy
a. Reduces keratinocyte proliferation
b. Has a slower onset of action than topical steroids, but yield longer disease-free periods
c. As effective as topical steroids (only ultra-potent steroids may have greater efficacy)
d. More irritating than topical steroids, but less potential for long-term toxicity compared
with steroids
d) Preference/Pearls
a. Often used in combination with topical steroids to enhance efficacy and reduce the risk of
atrophy, especially over the long term
b. Calcipotriene is deactivated by acidic products, and some steroids may be acidic. Best
practice is to apply one in the morning and the other at night.
e) Simplicity/Dosing
a. Twice daily application to affected areas; when used in combination with steroids, once
daily application is typically adequate.
b. Combination product with betamethasone dipropionate (Taclonex®) is dosed once daily
and is very effective, but very expensive
c. Vitamin D analogues are more expensive than steroids
Tazarotene (Tazorac®)
a) Safety
a. Pregnancy Category X
b. Photosensitivity
b) Tolerability
a. Increased sensitivity to environmental factors (wind, cold, heat)
 b. Skin burning, irritation, stinging, pruritus, erythema
c. Adverse effects are concentration and frequency dependent
c) Efficacy
a. A topical retinoid that modulates keratinocyte proliferation and differentiation
b. Takes longer to see clinical effect (about 12 weeks as opposed to 8 weeks with the other
agents)
c. Higher concentrations are more effective than lower concentrations but have more local
side effects

d) Preference/Pearls
a. Recommended to use with topical steroids for improved efficacy and improved
tolerability
b. To reduce incidence of irritation:
i. Use cream formulation
ii. Use lower concentration
iii. Combine use with moisturizers
iv. Apply on alternating days
v. Limit exposure to 30-60 minutes, then wash off (no reduction in efficacy)
vi. Apply with topical steroids
e) Simplicity/Dosing
a. Once daily application

Coal Tar 
a) Safety
a. Photosensitivity
b) Tolerability
a. Greasy, messy, can stain skin, hair, and clothing
b. Odor
c) Efficacy
a. Considered second line or alternative agent due to more effective and less messy options
b. Helpful as an adjunct to topical steroids
d) Preference/Pearls
a. Not for use in an acute exacerbation---will worsen acute psoriasis
b. Because coal tar is a keratolytic, it is generally reserved for use after the plaque has
completely formed
c. Is frequently compounded in triamcinolone cream 0.1% to use twice daily
e) Simplicity/Dosing
a. Available in many dosage forms, and without a prescription (inexpensive option)
b. Once or twice daily

Calcineurin inhibitors [tacrolimus, (Protopic®) and pimecrolimus (Elidel®)]

a) Safety
a. Not for use in patients < 2yo or immunocompromised patients
b. FDA black box warning for increased risk of lymphoma and skin cancer, although still no
definitive causal link has been established
b) Tolerability
a. Well tolerated
c) Efficacy
 a. Inhibits T cell activation and release of imflammatory cytokines
b. Only marginally effective in plaque psoriasis, but considered first line option in
intertriginous, facial, genital areas or inverse psoriasis
d) Preference/Pearls
a. Useful when steroid sparing agents are needed
e) Simplicity/Dosing
a. Twice daily dosing for no longer than 6 consecutive weeks
b. Do not apply to broken skin, active skin cancers, or active skin infections

Salicylic acid
a) Safety
a. Avoid using on large inflamed areas due to the potential of causing salicylism (n/v,
tinnitus, and hyperventilation)
b) Tolerability – skin irritation
c) Efficacy
a. Keratolytic- most useful at anatomic sites where thick scales are present
b. Usually used in addition to topical steroids or immunosuppressive agents for additive
effect
d) Preference/Pearls
a. Do not use in acute exacerbation (could make it worse)
b. The keratolytic effect enhances penetration and efficacy of other topical agents such as
topical steroids
c. Do not use in combination with UVB therapy because it will decrease the efficacy of the
phototherapy
e) Simplicity/Dosing
a. Available in many dosage forms and strengths (aerosol foam, soap bar, cream, gel, lotion,
shampoo)

Anthralin (Dritho-Scalp®; Psoriatec™)

a) Not as effective as topical steroids or vitamin D analogs
b) Apply at increasing contact intervals (starting at 5-10 minute intervals) and increased to 30
minutes per day as tolerated
c) Less cosmetically appealing due to staining of lesions, surrounding skin, hands, nails, and
clothing
d) Side effects: inflammation, irritation, red-brown staining of skin and clothing
e) Must ONLY apply to affected areas because contact with uninvolved skin may result in excessive
irritation and staining
f) Skin staining usually takes 1-2 weeks to disappear after stopping therapy

Systemic Therapy
 Should be reserved for patients with moderate to severe disease or refractory disease because the
risks associated with systemic therapy may be greater than those of the disease
 Questionable whether systemic therapy is as efficacious as biologics
 Monotherapy with systemic agents do not typically provide optimal outcomes, thus combos of
systemic agents with other modalities are often used for better efficacy, which often allows for
lower doses to be used with less chance of adverse effects
 In addition to combination therapy, other treatment strategies typically include rotational and
sequential therapy, especially when using biologics.
 o Rotational: using one agent for a limited time then switching to a completely different
regimen with different MOA, continuing on a rotational basis; this approach allows the
potential to minimize cumulative drug toxicity
o Sequential: involves rapid clearing of psoriasis with aggressive therapy followed by a
transitional period in which a safer drug is introduced at maximal dosing then decreased
to a maintenance dose along with other maintenance therapies.

Methotrexate (MTX)
a) Safety
a. Contraindicated in pregnancy and breastfeeding (teratogenic). Women who are planning
to become pregnant should discontinue use 3 months before conception
b. Significantly diminishes ability to generate an immune response
c. Increased incidence of the following:
i. Any malignancy
ii. Lung cancer
iii. Melanoma
iv. Non-Hodgkin lymphoma
d. Avoid in patients with the following:
i. CrCL < 30ml/min
ii. Platelet count < 50,000/mm3
iii. WBC count < 3000/mm3
iv. LFTs > 2x ULN (upper limit of normal)
b) Tolerability
a. Abdominal cramps, nausea, vomiting, anorexia
b. Hypersensitivity pneumonitis, pulmonary fibrosis
c. Increased LFTs, hepatotoxicity
d. Stomatitis, mucosal ulceration
e. Bone marrow suppression, infections
c) Efficacy
a. Indicated for moderate to severe psoriasis, those with psoriatic arthritis and/or nail
disease, and in those refractory to topical or UV therapy
b. Most widely used systemic agent for over 40 years; logical first choice systemic agent
because it is most cost effective systemic drug with the longest safety follow-up data
c. Has antiproliferative effects on DNA synthesis in epidermal cells; more recent evidence
points to immunosuppressive effects on activated T cells, and is a folic acid antagonist
d. Most commonly used when long term systemic therapy is needed
e. Effective at reducing symptoms of psoriasis but may be less effective than cyclosporine
and biologics
d) Preference/Pearls
a. Reserved for use in severe, intractable, and disabling psoriatic symptoms and/or psoriatic
arthritis
b. Reported as being slightly less effective than cyclosporine for psoriasis, but with fewer
adverse events that require discontinuing therapy
c. Cheaper alternative to biologics
e) Simplicity/Dosing
a. Initiate at 7.5-15 mg per week and increase incrementally by 2.5mg q2-4 weeks until
response is evident; max dose is about 25 mg per week
b. Can be given orally, SQ, IM, or IV; and can be used long term
 c. Administer with folic acid 1-5 mg per day to avoid stomatitis, nausea, and macrocytic
anemia. Folic acid does not appear to protect against pulmonary toxicity, and it is
uncertain whether it protects against hepatotoxicity
d. Concurrent use of other meds that interfere with folic acid metabolism (sulfa a major one)
can increase the toxicity of MTX. (There are NUMEROUS drug interactions)
 For patients with one or more risk factors for hepatotoxicity, use of a different systemic drug
should be considered.

******Hepatotoxicity and need for liver biopsy******

Risk factors for hepatotoxicity from MTX include:
History of moderate alcohol consumption Diabetes
Persistently elevated LFTs Obesity
History of liver disease, such as chronic hepatitis B or C Hyperlipidemia
Family history of inherited liver disease (eg, hemochromatosis) Absence of folate supplementation
History of significant exposure to hepatotoxic drugs (other than during MTX therapy
MTX) or chemicals

Patients WITHOUT risk factors for hepatotoxicity:
 Have LFTs drawn Q1-3 months
 If 5/9 LFT levels are ↑ over the course of 12
months, OR if albumin level is ↓ in the
context of normal nutritional status, liver
biopsy should be performed
 Also consider liver biopsy after a
cumulative dose of 3.5-4 g of MTX has
been administered; other options include
continuing to monitor without liver biopsy,
or simply switch to another agent
Patients WITH risk factor(s) for hepatotoxicity:
 Use other agent if not contraindicated
 If decision is made to proceed with MTX,
perform liver biopsy within 2-6 months of
initiating therapy
 Repeat liver biopsies after every 1-1.5 g
of cumulative MTX dose

Cyclosporine
a) Safety
a. Nephrotoxic (preferable to keep dose < 5mg/kg/day)- must monitor SCr regularly during
therapy
b. HTN – must monitor BP on regular basis during therapy
c. Do not use concurrently with UV phototherapy
d. Cutaneous squamous cell carcinoma and lymphoproliferative disorders (especially if use
exceeds 2 year period)
e. Avoid in patients receiving immunosuppressive agents or coal tar
f. Avoid use in patients with renal insufficiency, poorly controlled HTN, malignancy, major
infection, or poorly controlled diabetes
g. Hypertriglyceridemia (TGs >750 mg/dL)
h. Hypomagnesemia, hyperkalemia
i. Increased LFTs
b) Tolerability
a. GI intolerance, headaches
b. Paresthesias
 c. Hypertrichosis
d. Gingival hyperplasia
e. Flu-like symptoms
c) Efficacy
a. Used for severe cutaneous psoriasis and psoriatic arthritis
b. Improvement usually seen within 4 weeks with significant clearing in 8 weeks
c. Because of significant ADRs, typically is used on short term basis for quick control
d. Considered more efficacious than MTX and has more rapid onset, but the number and
degree of serious adverse events limits its use----generally used on short term basis for
quick control, or as bridge therapy during the induction of other maintenance agents that
take longer to see a response.
e. Efficacy is dose dependent, but doses beyond 5mg/kg/day are not recommended due to
the shift of risk>>>>benefit
d) Preference/Pearls
a. Reserved for patients who do not respond to at least one other systemic agent and cannot
use or tolerate biologics
b. Most commonly used as a short term course for severe flares as rescue or bridge therapy
due to its quick onset
c. NUMEROUS drug interactions
e) Simplicity/Dosing
a. Twice daily dosing for no longer than 1 year of continuous treatment
b. Initiate at 2.5 mg/kg/day. If inadequate response after 4 weeks, increase by 0.5-1
mg/kg/day at 2-4 week intervals to max dose of 5 mg/kg/day. If an adequate response has
not been achieved after 3 months of therapy at highest dose, discontinue therapy.
c. If good response is seen, lower dose by 0.5-1 mg/kg/day at 2 week intervals to the lowest
possible dose that maintains control.
d. Maintenance therapy with cyclosporine can be continued for up to 1 year, but intermittent
short term therapy (12-16 weeks) is the most frequently used regimen; when relapse
occurs, cyclosporine is reinstituted at the previously established effective dose

Acitretin (Soriatane®)
a) Safety
a. Pregnancy category X
i. Contraindicated in women who are pregnant or who intend to become pregnant
within 3 years of stopping drug.
ii. Women who want to use drug must commit to 2 forms of contraception 1 month
prior to starting drug and for 3 years after stopping the drug
iii. Must sign informed consent of fetal risks prior to starting therapy
iv. Boxed warning: female patients should abstain from ethanol during therapy and
for 2 months after stopping drug (combo with acitretin forms teratogenic
metabolite that would increase the duration of teratogenic potential)
v. Boxed warning: cannot donate blood during therapy or for 3 years following
completion of therapy
vi. Acitretin avg t1/2 is 50 hrs; metabolites cis-acitretin is approx.. 63 hrs, and
etretinate is 120 days; etretinate metabolite stored in adipose tissue and is
detectable up to 3 years after stopping drug.
b) Tolerability---adverse effects are dose dependent
a. Hypervitaminosis A (dry lips, chelitis, dry mouth, dry nose and eyes, conjunctivitis, dry
skin, pruritus, scaling, and hair loss)
b. Hepatotoxicity
c. Skeletal changes---therefore not approved for use in children
 d. Chronic elevations in triglycerides may increase risk of atherosclerosis---treatment with
fibrates is often necessary
e. “Unstable psoriasis”- like reaction (“retinoid dermatitis”)
c) Efficacy
a. Indicated for severe psoriasis
b. MOA not completely understood but decreases abnormal differentiation of keratinocytes
c. Most useful for pustular, palmar-plantar, and erythrodermic forms of psoriasis
d. Considered less effective than other traditionally used systemic agents when used as
monotherapy in plaque psoriasis, and is therefore considered more of an adjunct for this
indication

d) Preference/Pearls
a. Because of the lack of associated immunosuppression, it has particular value in patients
with known infection, active malignancy, or HIV
b. Has advantage of displaying little cumulative toxicity after use for extended periods of
time
c. Combo of acitretin and UVB or PUVA is highly effective and provides faster and more
complete clearance of lesions, while also allowing lower doses to be used of both agents
limited adverse effects
d. Also can be combined with cyclosporine and MTX for better efficacy
e) Simplicity/Dosing
a. Efficacy is dose dependent, and optimal treatment dose is 50 mg per day
b. Generally start with 25 mg po every other day then increase to 50 mg po QD WITH the
main meal to enhance absorption
c. Must monitor:
 Lipid profile (baseline and at 1- to 2-week intervals for 4-8 weeks)
 liver function tests (baseline, and at 1- to 2-week intervals until stable, then as
clinically indicated)
 blood glucose in patients with diabetes
 bone abnormalities (with long-term use)

Second-tier systemic agents – used less commonly, and considered for patients who do not respond to or
cannot tolerate commonly used systemic agents, and who cannot afford or be treated with biologics
 Azathioprine
 Hydroxyurea
 Leflunomide
 Mycophenolate mofetil
 Sulfasalazine
 Tacrolimus
 6-thioguanine

Biologic Therapy
1. Biologics are routinely used for moderate-severe psoriasis when one or more traditional systemic
agents fail to produce an adequate response, are not tolerated because of adverse effects, or are
unsuitable because of the presence of comorbidities
2. Treatment decisions are very complex, and patients who have failed one or more biologics may
still gain benefit from a different agent.
 3. Some biologics may be more efficacious than some older systemic therapies
4. Most of these agents are very expensive as well as the lab monitoring required, and cost
effectiveness is a major consideration in choosing to use biologics.
5. There is a concern that all TNF-α inhibitors have the potential to activate latent infections such as
TB and increased rates of infection have been seen in patients with RA.
6. TNF-α inhibitors have also been associated with an increased risk of malignancies, including
lymphoma and leukemia, opportunistic invasive fungal infections, and new onset psoriasis (in
people without psoriasis using the agents for other reasons). These conditions have resulted in a
black box warning for all TNF-α blockers.

Interleukin-12/ 23 Inhibitor [ustekinumab (Stelara™)]

a) Safety
a. Increased risk for infection and malignancy, including skin cancers due to MOA,
however 4 years of trials do not show an increased risk compared to expected rates in
general population
b. Rare reports of major adverse cardiovascular events in early phase 2 and 3 trials, however
pooled data from these trials with 5 years of follow-up do not show an increased risk
c. Pregnancy Category B
b) Tolerability
a. Occasional injection site reactions
b. Well-tolerated; safety data up to 4 years of use
c) Efficacy
a. PASI-75 in 67% of patients at 12 wk; of these patients, PASI-75 maintained at 52 wks for
87% of patients
b. Efficacy persists over time
c. In a head-to-head comparative trial with etanercept, ustekinumab had superior efficacy
for plaque psoriasis with similar adverse effects
d. Inferior efficacy (and even flares) for PsA versus the TNF-α blockers (according to phase
II trials—not head to head comparisons)….phase III studies for PsA are ongoing
e. Increased body weight is associated with decreased efficacy
f. MOA: Human monoclonal antibody that binds to and interferes with the proinflammatory
cytokines, interleukin (IL)-12 and IL-23. Biological effects of IL-12 and IL-23 include
natural killer (NK) cell activation, CD4+ T-cell differentiation and activation.
Ustekinumab also interferes with the expression of monocyte chemotactic protein-1
(MCP-1), tumor necrosis factor-alpha (TNF-α), interferon-inducible protein-10 (IP-10),
and interleukin-8 (IL-8). Significant clinical improvement in psoriasis patients is seen in
association with reduction of these proinflammatory signalers.
d) Preferences/Pearls
a. Place and read PPD before initiation
b. All immunizations should be UTD prior to therapy
c. Live vaccines should not be given concurrently. BCG vaccines should not be given 1
year prior to, during, or 1 year following treatment
d. Monitor CBC, LFTs, and hepatitis profiles at baseline with yearly PPD and periodic CBC
and LFTs
e) Simplicity/Dosing
a. ≤100 kg: 45 mg SQ at baseline, 4 wk, and then every 12 weeks thereafter
b. >100 kg: 90 mg SQ at baseline, 4 wk, and then every 12 weeks thereafter
Tumor Necrosis Factor (TNF-α) Inhibitors [etanercept (Enbrel®); infliximab (Remicade®);
Adalimumab (Humira®); golimumab (Simponi ®)
a) Safety
a. Increased risk of serious bacterial &/or fungal infections; contraindicated in those with
active, serious infections
b. Associated with reactivation of latent infections (TB, Hep B in carriers)
c. May increase risk of malignancy, including melanoma, leukemia, and lymphomas
d. Linked with new or worsening heart failure and possibly death in patients with heart
failure; do not use in patients with NYHA class III or IV CHF. Patients with NYHA class
I or II CHF should undergo cardiac ECHO; if EF<50% avoid TNF-α blockers.
e. Should not be used in patients with demyelinating diseases (MS) or in patients who are
first-degree relatives of those with MS
f. All are pregnancy category B
b) Tolerability
a. Headache, fevers, chills, fatigue
b. Abdominal pain, diarrhea
c. Injection site reactions; infusion related reactions
d. Upper respiratory tract infections, pharyngitis
e. Anaphylaxis and hypersensitivity reactions (urticaria, dyspnea, hypotension)
f. Anemias
c) Efficacy
a. Considered the biologic class of choice for PsA due to extensive safety and efficacy data;
all are considered equally efficacious for this indication
b. For cutaneous psoriasis phase III trials suggest efficacy is greatest with:
i. infliximab > adalimumab > etanercept > golimumab
c. However, over the course of a year, a loss of efficacy tends to be noted likely related to
development of antibodies, necessitating addition of MTX, phototherapy, or switching to
a different biologic
d. All TNF-α blockers have been combined with MTX to lessen the likelihood of
developing resistance to therapy
d) Preferences/Pearls
a. Immunizations should be UTD prior to initiation
b. Place and read PPD before administering
c. Do not use with live vaccines, biologically inactive or recombinant vaccines may be
considered although the immune response of these vaccines could be compromised
d. Perform yearly PPD, periodic monitoring of CBC, LFT

Etanercept (Enbrel®) Pearls

 Different from infliximab and adalimumab in that it is humanized, which minimizes the risk of
immunogenicity (lower incidence of infections)
 Only biologic to be studied for psoriasis in children 4-17 yo with data demonstrating efficacy;
although still not FDA approved for use in children for psoriasis indication.
 Has long term safety data in trial of up to 96 weeks of use.
 Dosing:
o Initial: 50 mg SQ twice weekly, 3-4 days apart (starting doses of 25 or 50 mg once
weekly have also been used successfully); maintain initial dose for 3 months
o Maintenance: 50 mg SQ weekly
Infliximab (Remicade®) Pearls
 Clears cutaneous psoriasis in the highest proportion of patients and with the greatest rapidity
 Superior to MTX in head to head trial (RESTORE1 Trial)
 Most patients achieve PASI 75 at week 10 (after 3 doses)
 Dosage: 5 mg/kg IV infusion over 2-3 hours @ week 0, 2, and 6 then every 8 weeks----$$$
 Great agent for maintenance treatment; two trials indicate sustained improvement 46 and 50
weeks out after induction when therapy is continued. Continuous treatment is preferred over
intermittent “prn” therapy due to lower incidence of serious infusion related reactions in the
continuous treatment arm (i.e. Continuous therapy= 5mg/kg q8 weeks after induction;
Intermittent treatment= reinduction with up to four 5mg/kg infusions of infliximab over 14
weeks).
 HOWEVER, RA and IBD studies indicate the development of infliximab-antibodies, which may
contribute to the loss of response to infliximab in some patients; impact of anti-infliximab
antibodies on treatment efficacy in psoriasis is unclear.
 No need to adjust in renal or hepatic impairment

Adalimumab (Humira®) Pearls

 Dose: 80 mg SQ x1 then 40 mg SQ every other week beginning one week after the initial dose
 Superior to MTX in head-to-head trial
 A small percentage of patients will lose efficacy after 12 weeks even with continued use

Golimumab (Simponi ®) Pearls

 Has indication for PsA; not cutaneous psoriasis due to lack of efficacy data in clinical trials
(PASI-75 achieved in only 40% of patients after 14 wks---looked at as a secondary outcome of
PsA clinical trials)
 Dosing: 50 mg SQ every 4 weeks

Drug Selection
 Limited plaque psoriasis (mild-moderate): responds well to topical steroids and emollients.
Alternatives are tar, tropical retinoids and calcipotriene or a combination of these.

 Severe disease: phototherapy or systemic therapy or biologics

 Facial or intertriginous areas: , class VI and VII topical steroids used sparingly or topical
tacrolimus or pimecrolimus may be used as alternatives or as corticosteroid sparing agents,
though improvement may not be as rapid. Also can use calcipotriene. Localized phototherapy is
another option for recalcitrant disease.

 Guttate: responds to UVB phototherapy +/- medium potency topical steroids

 Localized pustular: difficult to treat; systemic retinoids are first line; may also use topical potent
steroids or topical PUVA
 Erythrodermic: topical potent steroids, oral retinoid, MTX, or cyclosporine, or biologics with
rapid onset (infliximab)

 Nail psoriasis: VERY difficult to treat; potent class I or II topical steroids with calcipotriene, or
intralesional steroids. Systemic therapy, phototherapy and biologics are more effective than
topical therapy. Improvement is VERY slow as it takes 8-12 months to generate a new nail

PLAQUE PSORIASIS

Limited Disease
(Mild-moderate) Extensive Disease
(Moderate- severe)

First Line: First Line:

 Topical steroids &/or  Phototherapy first if possible
vitamin D analogs
 Emollients
If not possible or no effect:
Alternatives:  Systemic therapy or biologic
 Topical Tar
 Topical Tazarotene

Facial or Intertriginous: PSORIATIC ARTHRITIS

 Topical Calcipotriene
 Class VI-VII topical
steroids
 Topical calcineurin
inhibitors

Moderate to Severe
Mild

If no effect or recalcitrant
disease:
 Phototherapy is first 1st line: MTX +/- TNF-α blockers
line  NSAIDS
2nd line: ustekinumab +/- MTX
If no response after 2-3
months, consider MTX