Evaluation
Severity of Disease
The severity of psoriasis is defined by subjective and objective qualitative assessment based on BSA involvement, location, severity, number of lesions, response to topical treatments, associated physical disability, presence or absence of psoriatic arthritis, psychosocial effects, and impact on the quality of life of the patient.
The assessment of severity
may also be done using Psoriasis Area and Severity Index (PASI), Physician’s
Global Assessment (PGA), Patient’s Global Assessment, or Dermatology Life
Quality Index (DLQI).
PASI is more
specific in quantifying the extent and severity of psoriasis by taking into
account not only the BSA but also the intensity of plaque thickness, redness,
and scaling with scores ranging from 0 (no disease) to 72 (maximal disease
severity) but is rarely used in clinical practice. PASI
is the best validated tool which showed good internal consistency, good
intraobserver variation, and acceptable interobserver variation. PGA
measures psoriasis severity and response to treatment based on erythema, induration,
and scaling. DLQI is an important tool for the assessment of psoriasis severity
and the treatment response in clinical trials and is seldom used in clinical
practice. DLQI includes 10 questions addressing
symptoms, mental health, impact on daily life, leisure, work and school,
personal relationships, and the burden of psoriasis treatment.
Based on the guideline released by the American Academy of Dermatology last 2020, the severity of the disease may also be defined by the total BSA involved:
- BSA of <3%: Mild
- BSA of ≥3% but <10%: Moderate
- BSA of ≥10%: Severe
The assessment of the quality
of life is based on the patient’s coping strategies, daily activities, the presence
of distress, and the impact of disease on relationships.
Comorbidities that
affect the severity of psoriasis include psoriatic arthritis, IBD, psychological or psychiatric disorders, uveitis, cardiovascular
diseases, hepatic disease (eg impaired liver function, alcoholic liver
disease), malignancy (eg lymphoma), sleep apnea, chronic obstructive pulmonary
disease, renal disease, lifestyle choices (eg smoking, alcoholism), and metabolic
syndrome.
Principles of Therapy
The goals
of treatment include controlling the signs and symptoms, ensuring long-term effective
therapy to prevent complications, and enhancing and sustaining the patient’s
health-related quality of life. Treatment of psoriasis is composed of induction
and maintenance phases. The induction phase is the initial stage of therapy
aimed at quickly reducing the severity of psoriasis symptoms within the first 12-16
weeks. The maintenance phase follows the induction phase once the symptoms have
been controlled, aiming to sustain the achieved level of improvement and
prevent the relapse of severe symptoms. The choice of therapy in managing
psoriasis should be individualized based on age, the severity of the disease, the
presence of comorbidities, the cost of treatment, the risks and benefits of
treatment, patient preference, and healthcare services access, and is also based
on the shared decision between patients and healthcare providers. A treat-to-target
strategy is recommended wherein treatment is modified if treatment goal is not
achieved. The clinician should be familiar with all the treatment options so
that the right therapy can be chosen for each individual patient as most
patients will undergo multiple simultaneous therapies.
Mild or
mild-moderate disease can usually be treated by topical therapy alone while moderate-severe or severe
disease usually requires phototherapy or systemic therapy including biologic
agents. A treatment regimen can be modified to increase efficacy by increasing
the dose, decreasing dose intervals, adding a topical agent, adding another
systemic agent, or changing the drug. Combination
therapy may be considered when the patient fails to respond to monotherapy. Biologic
therapy is used as monotherapy and may be combined with topical agents (eg
corticosteroids, vitamin D analogues) or other systemic agents to increase
effectiveness or decrease potential adverse effects.
The
choice and frequency of therapy will be influenced by the severity of the
disease, BSA involved, body region involved, effect of psoriasis on the quality
of life, and degree of psychological impairment caused by the disease. Individual factors such as the patient's age and
weight, presence of comorbidities (eg hepatic disease, IBD, hypertension, heart
failure), plans for conception, treatment preference, and the likelihood of
treatment adherence may also affect the choice and frequency of therapy. The goals
of therapy, disease phenotype, activity pattern, presence of psoriatic
arthritis, and outcomes of prior psoriatic treatments should also be
considered. The risk versus benefit ratio must be considered for each treatment
regimen along with the availability and cost of therapy.
Vaccinations
One may consider administration of influenza, hepatitis A and B, tetanus-diphtheria, and pneumococcal vaccines prior to therapy. Once immunosuppressive therapy is initiated, live vaccines and live-attenuated vaccines should be avoided. Avoid live vaccinations in infants until 6 months of age if mothers have received biologic therapy beyond 16 weeks gestation.
Pharmacological therapy
Topical
Therapy
Topical
therapy is considered the first-line treatment for mild plaque psoriasis. It may be used as an adjunctive treatment for resistant localized
lesions in patients receiving phototherapy or systemic agents.
Emollients1
Emollients are considered
the standard adjunctive therapeutic approach to the treatment of psoriasis. They
are used in combination with other topical treatments. One study established
that the combination increases the efficacy of corticosteroids and provides
better control of psoriasis with lower doses of corticosteroids. They soften and
smoothen the stratum corneum, achieved by a trapping mechanism that decreases
the rate of transepidermal water loss. Emollients restore the epidermal barrier
function aiding in moisturizing dry skin, reducing scaliness and itchiness, and
enhancing the penetration of other topical agents. Proper skin hydration
prevents irritation and potential development of new lesions at trauma sites.
Patient preference and the
treatment area will determine the formula used (eg Petrolatum, Liquid paraffin,
Mineral oils, Glycerine). Petrolatum has a more occlusive but less humectant
effect than mineral oil.
1Various emollient products for psoriasis are available. Please
see the latest MIMS for specific formulations and prescribing information.
Calcineurin Inhibitors
Example drugs: Pimecrolimus,
Tacrolimus
Calcineurin inhibitors are indicated
for psoriasis located in the facial and intertriginous areas only. They are not
generally effective in plaque psoriasis. They work by blocking the synthesis of
inflammatory cytokines that have an important role in the pathogenesis of
psoriasis.
Corticosteroids
Corticosteroids are the first-line
treatment for patients with mild or limited psoriasis and for plaque psoriasis.
It is the primary agent for scalp psoriasis. They have anti-inflammatory, antiproliferative,
immunosuppressive, and vasoconstrictive effects.
Tachyphylaxis (development
of tolerance) leading to decreased efficacy and side effects from long-term
treatment may limit their use; hence, it should be used judiciously to obtain
maximum benefits with the minimum side effects.
They are available in
different potencies from mild to very high. Low-to-mid potency may be used on
the face, intertriginous areas, and sites that are susceptible to atopy. It
should not be used at any site for >8 weeks. Combination with vitamin D is recommended
as the initial treatment for adults with trunk and/or limb psoriasis. Mid-potency
steroids are recommended as the initial treatment for the scalp, face, flexures,
and genital psoriasis.
For high to very high-potency
corticosteroids, the highest-potency agents were found to be the most effective
followed by vitamin D analogues. They are used as short-term therapy for rapid control. Potent to very potent topical corticosteroids
are not advisable for use on the face, flexures, and genitals, over 4 weeks, and
in children <1 year old. Very high-potency corticosteroids may be used on
areas with thick chronic plaques.
The choice
of product will depend on the site of the lesion to be treated, the age of the patient,
patient preference, the severity or thickness of lesions, and steroid potency
and formulation. For the scalp, lotions, sprays, solutions, foams and gels are
preferred since they can be rubbed on the scalp. Low potency is recommended for
the face, and potent steroids should be avoided. For the body folds, cream or
gel of low potency is recommended. For the palms
and soles, very potent steroids are typically necessary, however, they are only
mildly effective. Ointment is preferred. Topical corticosteroids are used
concomitantly with moisturizers.
Use corticosteroids
as an adjunct with agents that are better tolerated and increase the potency of
corticosteroids during flare-ups and taper down when in remission. They are commonly
used in combination with vitamin D analogues, tar, topical retinoid, ultraviolet
(UV) light, or systemic agents. A flare-up of
psoriasis may occur upon discontinuation; hence, corticosteroid therapy should
be reduced slowly. Advise regular skin examination for all patients having
long-term treatment to assess atrophy.
Dithranol (Anthralin)
Dithranol is recommended
for the treatment of mild-moderate psoriasis for short contact and is an effective treatment for
large plaque psoriasis. It is commonly used as short-contact therapy (20 to 30
minutes) in an outpatient setting. It works by slowing down the proliferation
of stem cells and preventing T-lymphocyte activation so that normal
keratinization may occur.
It has lower efficacy than
more potent topical corticosteroids or vitamin D analogues. It is not suitable for large areas of small
lesions, flexure areas, or the face, and it may be used on the trunk and limbs
only when treatment with other topicals has failed. Staining and irritating
properties may limit its use.
Keratolytics
Salicylic acid is the most
commonly used keratolytic that is recommended for mild-moderate psoriasis.
Keratolytics remove hyperkeratosis, break down, peel off excess scales,
and soften the psoriatic plaques. They may be used alone or in combination with
other forms of therapy (eg corticosteroids and topical immunomodulators). The
combination is more effective because of increased skin penetration. Salicylic
acid in combination with topical steroids may be considered for the treatment
of moderate-severe psoriasis involving ≤20% of BSA, including palmar-plantar
psoriasis. It should not be used together with other oral salicylates or before
UVB phototherapy.
Retinoid
Tazarotene
is a topical retinoid that is effective in psoriasis. It may be used for the
treatment of mild-moderate psoriasis involving ≤10% of BSA, including
palmar-plantar psoriasis and nail psoriasis. It works by mediating cell
differentiation and proliferation.
It has similar efficacy to
topical corticosteroids, and it can achieve remission of psoriatic plaques. It
may be combined with topical corticosteroids to enhance therapeutic effects,
reduce the local irritation produced by retinoids, and reduce the treatment
duration.
Retinoids have a slow onset of action and when used as monotherapy, skin
irritation (retinoid dermatitis) may limit use. They are considered teratogenic
and therefore, should not be used in pregnant women or those planning to become
pregnant.
Roflumilast
Roflumilast
is a phosphodiesterase-4 (PDE4) inhibitor indicated for topical treatment of
plaque psoriasis, including intertriginous areas, in patients ≥12 years old. PDE4 inhibition affects the migration and actions of
pro-inflammatory cells including neutrophils and other leukocytes,
T-lymphocytes, monocytes, macrophages, and fibroblasts.
Tapinarof
Tapinarof is
an aryl hydrocarbon receptor-modulating agent indicated for the topical
treatment of plaque psoriasis in adults. It improves psoriasis via modulation
of T helper type 17 (Th17) cytokines (eg IL-17A and IL-17F), normalization of
the skin barrier, and antioxidant activity.
Tars2
Tars are effective for use
in chronic plaques in mild-moderate psoriasis. They reduce keratinocyte
proliferation by suppressing DNA synthesis, suppressing inflammation, and may
affect immunological function.
Tars may be used if vitamin
D analogues and corticosteroids are ineffective or not tolerated. They may also
be used alone as a tar bath or applied directly to psoriatic plaques and should
be avoided on the face and flexures.
They are most popularly
used as scalp treatment with corticosteroids or combined with UVB (Goeckerman
treatment). They may cause sterile folliculitis and have low patient tolerance
as most products are messy and odorous.
2Many tar preparations in combination with other psoriasis
medications are available. Please see the latest MIMS for specific formulations
and prescribing information.
Vitamin D Analogues
Examples: Calcipotriene (Calcipotriol), Calcitriol,
Maxacalcitol, Tacalcitol
Vitamin D analogues are indicated
in chronic plaque psoriasis, especially for long therapy and for patients with
mild-moderate scalp psoriasis. The combination of Calcipotriene and Betamethasone is recommended for 4-12
weeks for patients with mild-moderate scalp psoriasis and may be considered for
up to 52 weeks to prevent relapse. Tacalcitol or Calcipotriene combined with steroids
may be considered in patients with facial psoriasis. Calcipotriene or Calcitriol may be used alone or with topical
corticosteroids for intertriginous psoriasis. Calcitriol appears to be less
irritating on sensitive (eg skin folds) or intertriginous areas of the skin
compared with Calcipotriene. They inhibit keratinocyte proliferation and
enhance keratinocyte differentiation after binding to vitamin D receptors. Studies showed more improvement in psoriasis when used in
combination with topical corticosteroids than when either agent is used alone.
Other Topical Treatments
(Alternative Medicine)
Examples: Aloe vera, St John's wort, vegetable oils (VGO),
virgin coconut oil (VCO)
The above examples may be considered in patients with mild psoriasis
without contraindications. St John's wort should be used with caution in
patients undergoing phototherapy. Vegetable oils have a more pro-inflammatory
effect than virgin coconut oil. When
compared to vegetable oils, virgin coconut oil has a more occlusive and
humectant effect, diffuses more, has faster penetration on dry, thick, scaly
skin for cell repair, and has more anti-inflammatory effect.
Systemic Non-biologic Therapy
Systemic
non-biologic therapy is a recommended treatment for patients with moderate-severe
psoriasis. It is administered in intermittent or rotational regimens to prevent
cumulative toxicity. It is suitable for patients with good response and without
fast relapses. Treatment may be discontinued abruptly or tapered off when the
treatment goal has been achieved for a period of ≥6 months, when severe adverse
effects occur, upon the patient's request or when clinically indicated. Treatment
interruption may lead to recurrence or relapse and re-introduction of therapy
may be considered if PSA ≥5 and/or DLQI ≥5.
Indications
for systemic non-biological therapy include the following:
- Symptoms cannot be controlled by topical medications or
- Total well-being (psychological, physical, social) greatly affected or
- ≥1 of the following:
- Diagnosed moderate-severe or severe psoriasis or
- Localized, affected part significantly impaired or distressed or
- Failure of phototherapy (treatment failure or relapse >50% of baseline within 3 months)
Apremilast
Apremilast is a small
phophodiesterase-4 inhibitor that can inhibit inflammatory response by
regulating pro-inflammatory cytokines.
It is indicated in adult
patients with moderate-severe plaque psoriasis, especially for scalp and
palmar-plantar psoriasis, who are candidates for phototherapy or systemic therapy. It may
be used during induction therapy and for long-term therapy. It may also be
considered if an oral treatment is preferred, and the patient has inadequate
response, intolerance, or contraindications to conventional systemic agents.
Studies demonstrated a 75%
reduction in PASI score at week 16 as compared to the placebo.
Ciclosporin (Cyclosporine)
Ciclosporin inhibits T-cell
activation and is a potent immunosuppressant that binds cyclophilin which
inhibits calcineurin and blocks proinflammatory signaling.
It is reserved for
intermittent control and should not be given for >12 weeks unless clinically
indicated. It is effective for moderate-severe plaque-type psoriasis, severe
recalcitrant psoriasis, and erythrodermic, generalized pustular, and/or
palmoplantar psoriasis.
It is considered a first
line in treatment of patients with indications for systemic non-biologic
therapy and who need fast control of their disease, who have palmoplantar
pustulosis, need systemic therapy but have plans to have children in the future,
and had treatment failure after Methotrexate therapy or have disease flare-up
while on preexisting systemic therapy.
Combination
with topical Calcipotriene and Betamethasone is recommended for the treatment
of moderate-severe psoriasis. Ciclosporin has been used with topical vitamin D
analogue or Methotrexate which lowers the effective dose of both agents. It should
only be used by experienced practitioners and in patients who have failed
topical treatment, phototherapy, and other systemic treatments.
If possible, rotate its use
with other treatments or use it during severe inflammatory flare-ups. It should
only be used for <1 year since long-term use (>2 years) can lead to
nephrotoxicity and possible malignancies (eg squamous cell carcinoma and non-melanoma
skin cancers). Cyclosporine must not be
used concurrently with phototherapy (eg narrowband ultraviolet B [NB UVB] and Psoralen
plus ultraviolet A [PUVA]) and in patients with previous history of PUVA
exposure.
Corticosteroids
Systemic corticosteroids
are generally not recommended as they can lead to generalized pustular
psoriasis and rebound exacerbations. It should only be used if absolutely
needed. Intralesional steroids may be considered for unresponsive lesions and
areas with very thick lesions on glabrous skin, scalp, nails, palms, and soles.
Deucravacitinib
Deucravacitinib
is an oral tyrosine kinase 2 inhibitor indicated for the treatment of adults
with moderate to severe plaque psoriasis who are candidates for phototherapy or
systemic therapy. It is not recommended for use in combination with other
potent immunosuppressants.
Dimethyl fumarate
Dimethyl fumarate possesses
immunomodulatory, antiangiogenesis, and antioxidant effects. It is a recommended
option in adults with moderate-severe plaque psoriasis who are intolerant,
unresponsive, or with contraindications to other systemic agents (eg
Ciclosporin, Methotrexate) and PUVA.
Studies reported a significant
reduction in PASI score and improvement in quality of life as compared to the
placebo. Side effects like gastrointestinal disturbance and flushing may limit
use.
Hydroxyurea
Hydroxyurea inhibits DNA
replication and is an antimetabolite that can be effective as monotherapy,
though less effective than other systemic agents. It is a treatment option for
patients who fail topical therapies, UVB, or who cannot tolerate PUVA,
Methotrexate, or other systemic therapies.
Nearly half of the patients
who show improvement with Hydroxyurea develop bone marrow toxicity with
leukopenia or thrombocytopenia. It should be avoided in pregnant and breastfeeding
women.
Methotrexate
Methotrexate is an inhibitor
of folate biosynthesis and thereby impairing DNA replication and has cytostatic
and anti-inflammatory properties. It is an antimetabolite that may be used in
patients who have failed topical therapies and photochemotherapy.
It is the most frequently
used agent in moderate-severe, recalcitrant, and disabling psoriasis (psoriasis
covering >10% BSA). It is the first-line conventional systemic therapy for moderate-severe
psoriasis. It is highly effective, especially for the long-term
treatment of severe forms of psoriasis including psoriatic erythroderma and
pustular psoriasis. It is recommended to give subcutaneous dosing to patients
on oral treatment with a suboptimal response and consider it as the initial
route of administration in patients with high need.
Combination with topical
Calcipotriene is recommended for the treatment of moderate-severe psoriasis. Combination
with NB UVB may be considered for patients with generalized plaque psoriasis.
Methotrexate may be taken with
Folate supplements to reduce its toxicity. Side effects like bone marrow
depression, hepatotoxicity, or pneumonitis may limit its use; therefore,
monitoring of liver function tests, CBC, and renal profile is recommended. It
should be avoided in pregnant and breastfeeding women.
Mycophenolic acid
Mycophenolic acid is an antimetabolite initially developed for organ
transplantation that interferes with T-cell proliferation. Some reports show
beneficial effects in psoriasis patients. Many patients achieve long remissions,
but it may take up to 12 weeks to see maximal effects. As an immunosuppressant,
there is a small risk of developing lymphoproliferative disease and
non-cutaneous malignancies. In patients receiving this drug with other
immunosuppressants, pure red cell aplasia has been reported. It is avoided in
pregnant and breastfeeding women.
Retinoid
Retinoid modulates
epidermal differentiation and proliferation and possesses anti-inflammatory and
immunomodulatory properties.
Acitretin is the oral
retinoid of choice. It is an effective systemic agent that is not
immunosuppressive. It may be used as monotherapy for pustular, erythrodermic,
and moderate-severe plaque psoriasis. Its beneficial effect occurs much more
slowly when used for plaque and guttate psoriasis but improves dramatically
when combined with PUVA and UVB (lower doses of agents are required). It may be
combined with Calcipotriene, UVB, PUVA, and biologic agents.
Retinoids are highly teratogenic and tend to persist in body tissues;
hence, female patients should not become pregnant for 3 years after treatment
has been discontinued. It should likewise be avoided in patients taking
excessive amounts of vitamin A and in breastfeeding women. Mucocutaneous side
effects and dyslipidemia may also occur.
Sulfasalazine
Sulfasalazine is useful in moderate-severe plaque-type psoriasis. Its effects
are less than other systemic agents. Side effects are common but are not severe
and are typically reversible.
Tofacitinib
Tofacitinib interrupts the
Janus kinase/signal transducers and transcription signaling pathway activators
for cytokine activation. It may be considered for the treatment of
moderate-severe psoriasis. Multiple phase III clinical trials showed a 75%
reduction in PASI score at week 16 as compared to the placebo, with treatment
benefits experienced up to 2 years.
Nasopharyngitis was the most common side effect, while serious
infections (cellulitis, herpes zoster, urinary tract infection, pneumonia),
malignancies (lymphoma, lung cancer, breast cancer), lymphocytopenia, and dyslipidemia
were also reported.
Other Systemic Treatments
(Alternative Medicine)
Examples: Fish oil (omega-3 oil), curcumin
Fish oil may be considered an adjunctive treatment option to topical,
oral, and phototherapy in chronic plaque psoriasis. Oral curcumin supplements
may be used as an adjunctive treatment for psoriasis patients with varying
severity.
Biologic Therapy
Biologic therapy is considered for patients who have moderate to severe disease. Severe
disease is defined as having a PASI score of ≥10 and a DLQI of >10. Very
severe disease is quantified as having a total PASI score of ≥20 and DLQI of
>18.
In
addition to the severity of the disease, the patient should also have one of
the following clinical conditions:
- At high risk or has developed clinically significant drug-related toxicity and alternative standard therapy cannot be utilized
- Has contraindications to, intolerance or inaccessibility to, and/or failure to respond to phototherapy and standard systemic therapy (eg Methotrexate and Ciclosporin)
- Severe, unstable, life-threatening disease or severe localized psoriasis with significant impairment of function and/or high levels of distress
- Psoriatic arthritis making the patient eligible for anti-tumor necrosis factor (anti-TNF) agent therapy
Biologic therapy may be offered as first-line therapy to adults who meet the
criteria for biological therapy. A tumor necrosis factor (TNF) inhibitor or an
interleukin (IL)-17 antagonist (except Brodalumab) may be offered as a first-line
therapy to patients with both psoriasis and psoriatic arthritis. Biologic therapy must be
administered continuously without interruption to prevent recurrence.
Changing to an alternative
therapy, including another biologic agent, can be considered if the patient
does not meet the minimum response criteria, is initially responsive but loses
response, or if biologic therapy becomes intolerable or contraindicated. One
may consider dose escalation or interval reduction if with an inadequate
response to the first biologic therapy due to insufficient drug exposure.
It is important to assess patients for cancer risk and infection prior
to and during biologic therapy and monitor for adverse effects during and after
biologic therapy.
Anti-TNF-alpha
Adalimumab
Adalimumab is a human
anti-TNF-alpha monoclonal antibody that is indicated in patients with
moderate-severe chronic plaque psoriasis who are candidates for phototherapy or
systemic therapy. It is the recommended monotherapy for patients with moderate
to severe plaque psoriasis affecting the nails, palms, and soles (palmoplantar
psoriasis), and it may be a treatment option for those affecting the scalp. It
may also be considered in patients with erythrodermic or pustular psoriasis and
chronic plaque psoriasis. It is considered appropriate for long-term continuous
use. Studies showed that 80% of patients achieved 75% improvement in the PASI
score at week 12.
In order
to increase the efficacy of treatment of moderate to severe plaque psoriasis, a
combination with Methotrexate, topical agents (eg corticosteroids with or
without vitamin D analogues), or narrowband UV phototherapy may be considered. A
combination with Acitretin, Apremilast, or Ciclosporin may also be considered. Lastly,
rebound does not usually occur when discontinued but it may lose efficacy after
reinitiation.
Certolizumab pegol
Certolizumab pegol is a
recombinant, pegylated, humanized Fab fragment of an anti-TNF-alpha monoclonal
antibody that is indicated in adult patients with moderate-severe plaque
psoriasis. Three-year efficacy data pooled from CIMPASI-1 and CIMPASI-2 phase 3
clinical trials (after initial 48-week endpoint) showed a sustained and durable
response in patients dosed at 200 mg or 400 mg every 2 weeks demonstrating
long-term therapeutic benefits. It may be used as a first-line biologic agent
in women planning a pregnancy or when systemic therapy is needed during pregnancy.
In the CRIB study, no minimal placental transfer from mother to infant was
noted, suggesting lack of fetal exposure, thus supporting continuation of
treatment during pregnancy when needed. No to minimal Certolizumab pegol was
detected in breastmilk as demonstrated in the CRADLE study, thus treatment may
be continued during breastfeeding. While the risk of harm to pregnancy or
unborn infant from exposure to Certolizumab pegol cannot be completely ruled
out, evidence gathered through pharmacovigilance reporting suggests that
maternal exposure during the first trimester does not appear to increase the
risk of adverse neonatal outcomes or major congenital malformations.
Etanercept
Etanercept is indicated in
patients with moderate-severe plaque psoriasis. It is a recommended monotherapy
for patients with moderate-severe plaque psoriasis affecting the scalp or nails
and may be a treatment option in patients with inverse, erythrodermic, or
pustular psoriasis. The response is maintained for up to 24 weeks in patients
with severe chronic plaque psoriasis. Disease clearance may be improved when
combined with Methotrexate or NB UVB phototherapy.
Etanercept is considered in
patients who are unresponsive, intolerant, or have contraindications to other
systemic therapies, or where a short half-life is essential. It is a human
recombinant TNF receptor p75 fusion protein that inhibits TNF. Combination with
Acitretin, topical agents (eg corticosteroids with or without vitamin D
analogues), Apremilast, or Ciclosporin may be a treatment option to increase
efficacy in the treatment of moderate-severe plaque psoriasis.
Infliximab
Infliximab
is indicated in patients with moderate-severe plaque psoriasis. It may be a
treatment option for patients with moderate-severe plaque psoriasis affecting
the nails, palms, soles (palmoplantar psoriasis), and scalp. It may also be
considered in erythrodermic, inverse, or pustular psoriasis.
Infliximab is considered
for patients with very severe disease or when other biologic agents cannot be
used or have failed, or where weight-based dosing is important. Infliximab is a
human murine chimeric monoclonal antibody that inhibits TNF. It has high
binding affinity and specificity for TNF-alpha. It has a rapid clinical
response and is highly effective in initial exposure and in severe acute
flares.
Combination
with Methotrexate or topical agents (eg corticosteroids with or without vitamin
D analogues) may be a treatment option to increase efficacy in the treatment of
moderate-severe plaque psoriasis. Combination with Acitretin or Apremilast may
be considered to increase efficacy in the treatment of moderate-severe plaque
psoriasis. It has variable efficacy after restarting or beyond the first year
of continuous use.
IL-12/23 Inhibitor
Ustekinumab
Ustekinumab is indicated in
patients with moderate-severe plaque-type psoriasis. It may be a treatment
option for patients with moderate-severe plaque psoriasis affecting nails,
palms, and soles (palmoplantar psoriasis). It may be considered in patients
with moderate-severe plaque psoriasis affecting the scalp or with erythrodermic
or pustular psoriasis. It is considered in patients who are unresponsive,
intolerant, or have contraindications to other systemic therapies. It is a
human monoclonal antibody that targets IL-12 and IL-23 on the p40 subunit. It
may be combined with Acitretin, Methotrexate, or narrowband UV phototherapy to
increase efficacy in the treatment of moderate-severe plaque psoriasis in
adults. Combination with topical agents (eg corticosteroids with or without
vitamin D analogues), Apremilast or Ciclosporin may be considered to increase
the efficacy in the treatment of moderate-severe plaque psoriasis.
IL-17 Inhibitors
Bimekizumab
Bimekizumab
is a humanized IgG1-kappa monoclonal antibody with 2 identical antigen binding
regions that bind and neutralize IL-17A, IL-17F, and IL-17A/F cytokines. It is
indicated in patients with moderate-severe chronic plaque psoriasis.
Furthermore, it has been found to have superior efficacy compared to
Adalimumab, Secukinumab, Ustekinumab, and placebo for moderate-severe plaque
psoriasis in the BE SURE, BE RADIANT, and BE VIVID phase 3 trials,
respectively. Bimekizumab given every 4 or 8 weeks showed rapid response and
complete skin clearance at 16 weeks which was maintained through week 52 in the
BE VIVID phase 3 trial and up to week 56 in the BE SURE and BE READY phase 3
trials with both dosing schedules. The BE RIGHT open-label extension of the BE
VIVID, BE SURE, and BE READY phase 3 trials showed durability of results
through maintained efficacy response of up to 4 years.
Brodalumab
Brodalumab is indicated in patients
with moderate-severe plaque psoriasis. It may be a treatment option in adult
patients with generalized pustular psoriasis. It is a human monoclonal antibody
that binds to IL-17 receptor A (IL-17RA) and blocks the biologic activities of
IL-17A, IL-17F, IL-17A/F, and IL-17E.
Ixekizumab
Ixekizumab is indicated in
patients with moderate-severe plaque psoriasis. It may be a treatment option
for patients with moderate-severe plaque psoriasis affecting the nails or scalp
and those with erythrodermic or pustular psoriasis. It is a humanized IgG4
monoclonal antibody with neutralizing activity against IL-17A.
Secukinumab
Secukinumab is indicated in
patients with moderate-severe plaque psoriasis. It is a recommended monotherapy
in patients with moderate-severe plaque psoriasis affecting the nails or those
with moderate-severe palmoplantar plaque psoriasis. It may be a treatment
option in patients with moderate-severe plaque psoriasis affecting the head,
neck, and scalp or in patients with moderate-severe palmoplantar pustulosis. It
may also be considered an option in patients with erythrodermic psoriasis. Secukinumab
is a recombinant human monoclonal antibody that binds IL-17A.
IL-23 Inhibitors
Guselkumab
Guselkumab is indicated in
adult patients with moderate-severe plaque psoriasis. It is the recommended
monotherapy in adult patients with nail, scalp, and plaque-type palmoplantar
psoriasis. Guselkumab is a human IgG1 lambda monoclonal antibody that blocks
p19 subunit of IL-23. It has been found to have a better response in patients with
an inadequate response to treatment with Ustekinumab.
Risankizumab
Risankizumab is indicated
in patients with moderate-severe plaque psoriasis. It is a humanized IgG1
monoclonal antibody that selectively binds to the human IL-23 cytokine's p19
subunit and inhibits its interaction with the IL-23 receptor.
Tildrakizumab
Tildrakizumab is indicated
in patients with moderate-severe plaque psoriasis. It is a humanized IgG1 kappa
monoclonal antibody that selectively blocks IL-23 by binding to the p19 subunit.
Other Biologic Therapies
Alefacept
Alefacept
was previously indicated in adult patients with moderate-severe plaque
psoriasis candidates for phototherapy or systemic therapy but is no longer
marketed.
Efalizumab
Efalizumab was previously
indicated in patients with moderate-severe chronic plaque psoriasis but is no
longer marketed due to reports of progressive multifocal leukoencephalopathy.
Itolizumab
Itolizumab is indicated in
patients with active moderate to severe chronic plaque psoriasis who are
candidates for systemic therapy. Clinical trials have shown favorable clinical
effects and safety profile with monotherapy in patients with moderate to severe
plaque psoriasis who failed to respond to conventional systemic therapies. It
is a monoclonal antibody against T cell costimulatory CD6, it has
immunomodulatory and anti-inflammatory effects.
Spesolimab
Spesolimab
is indicated for the treatment of generalized pustular psoriasis flares in
adults. It is a humanized IgG1 monoclinal antibody that binds to IL-36 receptor
thereby inhibiting IL-36 signaling and preventing proinflammatory and
profibrotic pathway activation.
Nonpharmacological
Patient Education
Patient and family education is the key to successful management. The patient should understand that psoriasis isa chronic disease and treatment will only control the symptoms but not cure it. Assure the patient that psoriasis is quite common and not contagious.
Discuss various therapeutic options, risks and benefits, side effects, and expected results. Emphasize theimportance of adherence to treatment. Discuss the possible exacerbating factors such as medications (eg beta-blockers, Lithium, and antimalarials) and bacterial or viral infections.
Encourage a healthy lifestyle including regular exercise, maintenance of ideal body weight (BMI of 18.5-24.9kg/m2), non-to-mild alcohol consumption, smoking cessation, and gluten-free diet (may benefit patients with psoriasis with confirmed celiac disease).
Patients with any type of psoriasis should be informed of a potentially increased risk of coronary artery disease. Advise patients to follow up yearly, especially for the first 10 years from the initial diagnosis.
Alternative
Treatments
Stress
reduction techniques (ie meditation), cognitive behavioral therapy, and guided
imagery as adjunctive therapy may help improve psoriasis severity. Hypnosis as
a therapeutic adjunct for mild-moderate psoriasis may be considered in highly
hypnotizable patients who are willing to undergo this process. For patients
with mild-moderate or chronic plaque psoriasis who are interested in
acupuncture, this may be considered as an adjunctive treatment depending on
availability and patient preference.
Phototherapy or Photochemotherapy
Phototherapy is generally used in
patients with moderate-severe psoriasis, with psoriasis in vulnerable areas that
are unresponsive to topical therapy or other mitigating symptoms are present or
in patients who do not wish to receive conventional systemic or biologic
therapy. Phototherapy
is safe and efficacious without the potent adverse effects of systemic and immunosuppressive therapies. The
choice of phototherapy modality is based on the availability, efficacy, safety,
and ease of therapy. It is usually given 3 times a week during the treatment
phase then tapered to the lowest frequency needed to maintain symptom
improvement. Review the patient’s medical history and review systems to verify
that the patient does not have photosensitive diseases or medications (eg
history of ionizing radiation). Phototherapy is contraindicated in patients
with a history of melanoma or extensive non-melanoma skin cancer.
Lubricants
and emollients are needed for the efficacy of phototherapy. If possible, sunblock should be applied to
unaffected skin. Advise patients to protect the breast, ocular, and genital
areas during phototherapy sessions. Absolute
contraindications to phototherapy or photochemotherapy include
photogenodermatoses (eg Bloom syndrome, Cockayne syndrome, Rothmund-Thomson
syndrome, trichothiodystrophy, xeroderma pigmentosum), disorders with genetic
predisposition to skin cancers (eg albinism, Gorlin syndrome), concomitant oral
immunosuppressive medications (eg Azathioprine, Ciclosporin, Mycophenolate
mofetil, Tacrolimus), and being medically unfit and unable to stand safely (eg severe
cardiovascular disease or respiratory disease, poorly controlled epilepsy).
Broadband Ultraviolet B (BB UVB)
BB UVB is typically used in failed topical treatment, chronic stable plaque psoriasis, or guttate psoriasis. It is considered inferior in efficacy to topical PUVA monotherapy, and to narrowband UVB and oral PUVA monotherapy for generalized plaque psoriasis in adults.
The most effective spectrum of UVB phototherapy in psoriasis is 290-320 nm. It takes an average of 20 to 25 treatments to induce clearance and is given 3 to 5 days per week.
Clear emollients (eg petrolatum or mineral oil) improve the optical properties of the skin and should be applied prior to UVB treatment. UVB plus topical or systemic treatments can achieve more effective results and have a faster onset. It may also be combined with topical vitamin D analogues (after UV exposure), topical coal tar, PUVA, topical retinoid, low cumulative dose of systemic Methotrexate, or low dose of oral retinoids (eg Acitretin for generalized plaque psoriasis in adults).
The short-term adverse reactions include erythema, itching, burning, and stinging, while the long-term adverse effects include photoaging and dermatoheliosis.
Narrowband Ultraviolet B (NB UVB)
NB UVB consists
of utilizing a UV light spectrum of around 311 nm. It is recommended for
patients with >50% baseline disease severity 3 months after treatment, in
patients at high risk for skin cancer, and as monotherapy for plaque psoriasis
in adults and guttate psoriasis irrespective of age. It is recommended for patients with an inadequate response to
topical therapy or when topical therapy is not suitable before considering
systemic immunosuppression or immunomodulation therapies including PUVA. It is recommended
as a short-term rescue therapy to manage flares in patients undergoing systemic
therapy (eg Acitretin, Apremilast, biologic agents, Fumaric acid ester agents,
Methotrexate).
It is considered superior to BB UVB but not as effective as PUVA. It is recommended over BB UVB monotherapy for generalized plaque psoriasis in adults. Though less effective than PUVA, NB UVB appears to be safer, more convenient, and less costly than PUVA.
It takes an average of 15-30 treatments to induce clearance and is given 2-3 times per week. It is more effective than BB UVB with clearance within 2 weeks of treatment.
It may be combined with oral retinoids or Apremilast in patients with generalized plaque psoriasis who had an inadequate response to monotherapy. Concomitant topical treatment with corticosteroids, retinoids, and vitamin D analogues can be used safely.
The short-term adverse reaction includes burning while the long-term adverse effect is an increased risk for skin cancer.
Oral Psoralen Plus UVA (PUVA)
Oral PUVA is recommended for adult psoriasis. Psoralen is usually taken orally 90-120 minutes prior to administration of UVA radiation.
Short-term monotherapy is more effective than NB UVB for adult psoriasis. It is highly effective in the treatment of moderate-severe plaque, guttate-pattern psoriasis that cannot be controlled by topical therapy and with the potential for long remissions.
Up to 90% of patients achieve improvement or clearing of plaques after 20-30 treatments and it is given 2-3 times per week.
Patients must wear protective eye gear and sunscreens must be used throughout the day due to the photosensitizing effect of psoralens.
PUVA with topical or systemic treatments can achieve more effective results and have a faster onset. It may be combined with a low dose of oral retinoids, systemic Methotrexate (only for very severe psoriasis), vitamin D analogues, topical retinoids, topical steroids, or UVB.
The short-term adverse reactions include erythema, irregular pigmentation, xerosis, pruritus, and nausea or vomiting while the long-term adverse effects include cutaneous malignancies (eg squamous cell carcinoma and possible melanoma) which are usually dependent on the cumulative dose, increased risk of photodamage, and lentigines. Lifetime exposure should be limited to 200 PUVA sessions to minimize the risk of cancers.
Soak or Bath PUVA
Soak or bath PUVA is recommended in adults with moderate-severe plaque psoriasis.
Soak PUVA is used in patients with localized palmoplantar psoriasis prior to UVA exposure.
Bath PUVA is safe and effective for the treatment of patients with generalized stable plaque psoriasis. It has a lower UVA cumulative dose and fewer adverse effects and drug interactions when compared to oral PUVA, hence, it may be preferred by some patients over oral PUVA. It may be an alternative in patients with generalized psoriasis who cannot tolerate oral psoralens.
Topical PUVA
phototherapy is superior to localized NB UVB in adults with localized plaque
psoriasis, especially palmoplantar psoriasis and palmoplantar pustular
psoriasis.
Psoriasis_Management308-nm Excimer Laser and Excimer Light
Three hundred and eight nanometer excimer laser and excimer light are recommended for localized mild-moderate plaque psoriasis involving <10% BSA, including palmoplantar psoriasis. They may also be used in patients with extensive disease or for individual lesions. The excimer laser is more effective than excimer light for adults with localized plaque psoriasis and is recommended for adults with scalp psoriasis.
An average of 10 to 12 treatments are needed to induce clearance and are given 2 to 3 times per week. Patients may be in remission for up to 2 years. The excimer laser may be combined with topical corticosteroids in adult patients with plaque psoriasis.
They specifically target the affected skin and spare the uninvolved skin using a reduced cumulative dose thereby decreasing the long-term risk of malignancy. Common side effects with lower doses are erythema and hyperpigmentation while erosions, blistering, and crusting may occur with higher doses.
Other Phototherapy Modalities
Pulsed dye laser may be considered for patients with nail psoriasis. Evidence is sufficient to support the use of climatotherapy and Goeckerman therapy for psoriasis treatment.
