Psoriasis evidence based treatment

1. SEMINAR PRESENTATION
PSORIASIS: EVIDENCE
BASED TREATMENT
Moderator
Dr. Deepak K. Mathur

2. Guidelines of care for the management and
treatment
of psoriasis with topical therapies
GENERAL PRINCIPLES
• App. 80% of pts affected have mild to moderate
disease
• Majority of these patients can be treated with topical
agents
• Used as monotherapy or adjunctive
• T/t should be tailored to meet individual pts need
• Choice of vehicle can significantly alter use and
penetration of medication and so efficacy

3. • Use can be both intermittent and long-term
• Adherence is a major issue, being generally poor in
majority of pts

4. CORTICOSTEROIDS
Indication: Plaque-type psoriasis
Dosing:
• Can be used as monotherapy 1-2 times daily
• Combined with other topical agents, UV light, and systemic
agents
Duration of dosing:
• Class I steroids: available data for 2-4 weeks of treatment
• Less potent agents: optimal end point unknown
• Gradual reduction in usage recommended following clinical
response;unsupervised continuous use is not recommended
• For clobetasol and halobetasol, maximal weekly use should be
50 g or less

5. Short-term results:
• Highly potent agents have greater efficacy than less potent
agents (Br J Dermatol 2002)
Long-term results:
• Combination with other topicals and variations in dosing
schedules may lessen risk of long-term side effects
Toxicities:
• Local—skin atrophy, telangiectasia, striae, purpura, contact
dermatitis, rosacea
• Systemic—HPA axis suppression may occur with use of
medium- and high-potency topical steroids (JAAD1987);
• This will be lessened by intermittent or localized use

6. • Increased IOP, glaucoma, and cataracts have been
reported with use around eye
• Risks increase when used with excessive frequency or
duration
• Choice of the appropriate potency corticosteroid and
its vehicle should take into consideration
Intralesional corticosteroid therapy -valuable
technique in troublesome, small, resistant lesions on
backs of hands, especially knuckles, intensely pruritic
small plaques or lichenoid lesions

7. Baseline monitoring: None
Pregnancy: Category C
Nursing: Unknown safety
Pediatric use:
• Because of increased skin surface/body mass ratio,
risks to infants and children may be higher for
systemic effects secondary to enhanced absorption
• Growth retardation is also a potential concern

8. VITAMIN D ANALOGUES
Indication: Plaque-type psoriasis
Dosing: Twice daily to affected areas. Calcitriol and
three synthetic analogues, calcipotriol,tacalcitol,
maxacalcitol are used
Efficacy:
• In two large studies of plaque-type psoriasis , 70% to
74% showed marked improvement (JAAD 1995)
• Combination of calcipotriene and betamethasone
ointment: Studies showed better results with no drugrelated serious adverse events (Br J Dermatol 2006 )

9. • Systematic reviews of calcipotriol therapy for psoriasis attest
to its equivalence or superiority to other available topical
therapies apart from potent topical corticosteroids(BMJ 2000)
Contraindications/adverse reactions:
• Irritation in lesional and perilesional skin that is transient
• Reversible elevation of serum calcium—more likely to occur
patients treated with > 100 g/wk
• Causes photosensitivity, but no C/I to combining with UVB
phototherapy; when using combination
• Since calcipotriene is inactivated by UVA, it is important to
apply calcipotriene after and not before UVA exposure
(Arch Dermatol 1995)

10. Pregnancy and nursing: Category C
• No information on excretion in breast milk; pregnant
and nursing mothers were excluded from clinical
studies
Pediatric use: Calcipotriol (50 μg/g) ointment has also
been shown to be effective and safe in children when
administered in amounts up to 45 g/week/m2
(Br J Dermatol 1996)

11. TAZORETENE
Efficacy: 50% or more improvement, seen in 63% and 50% of
patients treated with tazarotene 0.1% gel and 0.05% gel,
respectively, once daily for 12 weeks (JAAD 1997)
• Best used in combination with topical corticosteroids
• Probably best reserved for thick, recalcitrant plaques of
psoriasis
Contraindications/adverse reactions:
• M/c side effect is skin irritation in lesional and perilesional
skin
• Photosensitizing
Pregnancy and nursing: Pregnancy category X

12. TACROLIMUS AND PIMECROLIMUS
Indications: No FDA-approved indications for psoriasis; primary
indications for off-label use are for facial and intertriginous
psoriasis
Efficacy:
• Plaque psoriasis: Not generally effective
• Intertriginous and facial psoriasis: Effective (JAAD 2004)
Contraindications/adverse reactions: burning and itching
Pregnancy and nursing: Category C
• not recommended for nursing mothers
Pediatric use: > 2yr

13. Non-medicated topical
moisturizers
Indications: use of emollients represents an internationally
accepted standard adjunctive therapeutic approach
Dosing: Applied once to 3 times daily
Efficacy: Two controlled studies of aloe vera had
conflicting results(J Eur Acad Dermatol Venereol
2005)
• These agents are thought to function by forming a film
on skin surface to help retain moisture

14. Salicylic acid
Efficacy: Data are limited on salicylic acid used alone
• Used in combination
Contraindications/adverse reactions: Do not combine salicylic
acid with other salicylate drugs
• Systemic absorption, although rare, can occur
• Salicylic acid decreases the efficacy of UVB phototherapy
because of a filtering effect and should not be used before
UVB phototherapy
Pregnancy/nursing: safe choice
Pediatric use: should be avoided in children

15. Anthralin
Indications: Use has been declined these days
Dosing: commonly used as short-contact therapy, starting at 1%
concentration with increasing concentration over time as
tolerated
• study showed that a 2-h short-contact regimen using dithranol
in Lassar’s paste was as effective as a standard 24-h Ingram
regimen
• 2% dithranol in Lassar’s paste applied for 2 h once daily was
therefore recommended as optimal for home use in wellmotivated patients (Br J Dermatol 1985)

16. Efficacy: Limited placebo-controlled trial data, but as
monotherapy, anthralin appears to have lower
efficacy than more potent topical CS or vitamin D
derivatives
Contraindications/adverse reactions: skin irritation and
staining
• have led to the development of combination therapy
and new formulations of dithranol
Pregnancy/nursing: Category C
Pediatric use: Use with caution

17. Coal tar
Indications: use has been declined
Efficacy: effective but less than topical corticosteroids
Contraindications/adverse reactions: poorly tolerated
• S/E include staining of clothes and tar odor, irritant
contact dermatitis, folliculitis, and photosensitivity
• carcinogenic in animals but in humans, there are no
convincing data proving carcinogenicity
Pregnancy/nursing: small risk(Acta Derm Venereol 1999)
Pediatric use: Use with caution

18. • use in psoriasis was popularized by
Goeckerman and, for more than half a century
since, his regimen of daily application of 2–5%
crude coal tar, combined with a tar bath and UV
light, has been a mainstay of in-patient treatment
(Arch Dermatol Syphilol 1931)

19. COMBINATION OF TOPICAL
THERAPIES
Corticosteroids and salicylic acid
• salicylic acid enhance efficacy of corticosteroids by
increasing penetration (Clin Ther 1998)
Corticosteroids and vitamin D analogues
• Combination is more efficacious than either therapy
alone, with fewer S/E (Dermatol Online J 2003)

20. Corticosteroids and tazarotene
• A clinical trial comparing tazarotene gel plus
mometasone cream to mometasone cream alone
showed superior efficacy of the combination (Int J
Dermatol 2001)
• Another potential advantage of using combination
tazarotene and topical corticosteroid is a potential
decrease in steroid-induced atrophy (Int J Dermatol
2001)
Tacrolimus and salicylic acid
• Improved efficacy with the addition of salicylic
acid(Arch Dermatol 2005)

21. COMPARISON STUDIES OF TOPICAL
THERAPIES
Vitamin D analogues
• While vitamin D analogues usually have a slower onset of
action than topical CS, they tend to yield longer disease-free
periods (J Dermatolog Treat 2003)
• A systematic review of efficacy and tolerability of calcipotriol
revealed that it is more effective for mild to moderate chronic
plaque psoriasis than either coal tar or short-contact anthralin
and that only potent topical corticosteroids have comparable
efficacy at 8 weeks of treatment (BMJ 2000)

22. Tazoretene
• In a multicenter study pts treated with tazarotene plus
mometasone achieved significantly greater reductions in BSA
involvement than did patients treated with calcipotriol alone
(Clin Ther 2000)
Tacrolimus and pimecrolimus
• In a 6-week randomized, double-blind study of 5o pts with
intertriginous and facial psoriasis, tacrolimus was more
effective than calcitriol (Br J Dermatol 2007)

23. SYSTEMIC THERAPY

24. GENERAL PRINCIPLES
• Although a minimum BSA , eg, 10%, has been traditionally
used as a prerequisite to starting a systemic therapy for
psoriasis, a subset of patients with limited disease have
debilitating symptoms
• For ex. although severe psoriasis of the palms and soles or
severe scalp psoriasis affects <5 % BSA, significant negative
affect on quality of life of patient makes a systemic approach
to T/t appropriate

25. Methotrexate
Indication: severe, recalcitrant, disabling psoriasis that is not
adequately responsive to other forms of therapy
Dosing: methotrexate is administered as a weekly single oral
dose
• Doses can be increased gradually until an optimal response is
achieved; total dose should not ordinarily exceed 30 mg/wk
• Doses should be reduced to lowest possible amount of drug
needed to achieve adequate control of psoriasis with
concomitant topical therapy
• A test dose of 2.5-5 mg is recommended

26. Folate supplementation
• Although the majority of experts recommend that all patients
treated with MTX receive folate supplementation
• But there are lots of controversies how to give folic acid
• Although a literature review of these data, largely derived
from the RA literature, suggests that low-dose folate
supplementation may reduce the hematologic, GI, and hepatic
side effects of methotrexate without decreasing the efficacy
•
(J Am Acad Dermatol 2005)

27. Absolute contraindications Relative contraindications
•
•
•
•
Pregnancy
Nursing mothers
Alcoholism
Alcoholic liver disease or other
chronic liver disease
• Immunodeficiency syndromes
• Bone-marrow hypoplasia,
leukopenia, thrombocytopenia,
or significant anemia
•
•
•
•
•
Abnormalities in renal function
Abnormalities in liver function
Active infection
Obesity
Diabetes mellitus

28. Toxicity
• Elevated LFT results - Minor elevations of LFT results are common;
if elevation exceeds 2 normal, must check more frequently; if
exceeds 3 normal, consider dose reduction; if exceeds 5 normal,
discontinue
• Anemia, aplastic anemia, leukopenia, thrombocytopenia
• Interstitial pneumonitis
• Ulcerative stomatitis
• Nausea, vomiting, diarrhea
• Malaise or fatigue
• Chills and fever
• Dizziness
• Decreased resistance to infection
• GI ulceration and bleeding
• Photosensitivity (‘‘radiation recall’’)
• Alopecia

29. Drug interactions
• Hepatotoxic drugs: eg, barbiturates
• Acitretin has been used successfully in combination
with MTX despite the potential for hepatotoxicity
from both medications
• Drugs that interfere with renal secretion of MTX : eg,
sulfamethoxazole, NSAIDs, and penicillins
• Folic acid antagonists: eg, trimethoprim

30. Liver biopsy
• Patients at low risk - at baseline, not necessary
• First biopsy: 3.5-4 g; subsequent biopsies to be
considered after 1.5 g
• Patients at high risk including history of diabetes,
obesity, abnormal LFT results, excessive alcohol
ingestion, chronic liver disease, family history of
heritable liver disease
• Consider baseline biopsy or at 6 mo with subsequent
biopsies after 1-1.5 g

31. Baseline monitoring
• History and physical examination
• CBC and platelet counts
• BUN, creatinine, and LFTs
• Liver biopsy is only indicated in patients with a
history of significant liver disease
• Pregnancy test and test for HIV in selected patients
• Consider PPD
• Consider chest radiograph if patient has underlying
pulmonary disease

32. Ongoing monitoring
• CBC and platelet counts at varying intervals (initially every 24 wk for first few months and then every 1-3 mo
• LFTs at monthly intervals, BUN, creatinine every 2-3 mo
• Pregnancy test if indicated
• Consider liver biopsy in patients at high risk
• For those without risk factors, consider liver biopsy in patients
with cumulative doses of more than 3.5-4 gm methotrexate
• For patients without risk factors, consider repeated liver
biopsies after each subsequent 1.5-g dosage
• Aminoterminal peptide of procollagen III is used as a test for
hepatic fibrosis, reducing the need for frequent liver biopsies

33. Pregnancy: category X; men and women considering conception
should be off methotrexate for 3 mo before attempting to
conceive
Nursing: mothers receiving MTX should not breast-feed
Pediatric use: low-dose methotrexate has been used effectively
and safely in children for a variety of dermatologic and
rheumatologic disorders (Pediatr Dermatol 1994)
Psoriatic arthritis: although there are only two small controlled
trials evaluating methotrexate for psoriatic arthritis that are
inadequately powered to assess clinical benefit
• MTX is often used as the primary agent to treat psoriatic
arthritis

34. Cyclosporine
Indication: adult, non immunocompromised patients with severe,
recalcitrant psoriasis
• Severe - extensive or disabling plaque psoriasis
• Recalcitrant - those patients who have failed to respond to at
least one systemic therapy or in patients for whom other
systemic therapies are contraindicated, or cannot be tolerated
• Some guidelines suggest use of cyclosporine in moderate to
severe psoriasis
• Efficacy observed in erythrodermic psoriasis, generalized
pustular psoriasis, and palmoplantar psoriasis

35. Dosing: 2.5-5.0 mg/kg/d in two divided doses/d
• Dose adjustments downward (by 0.5-1.0 mg/kg) when
clearance is achieved or when HT or decreased RFT
results are observed
Duration of dosing
• Optimally used as interventional therapy; may be
repeated at intervals after a rest period
• US approval: 1 y continuous treatment; non-US
approval: 2 y continuous treatment

36. Short-term results
• At 3 and 5 mg/kg/d, 36% and 65%, respectively,
achieved a clear or almost clear result after 8 wk
• After 8-16 wk, 50%-70% of patients achieve PASI 75
(Br J Dermatol 1999)
Long-term results
• Not recommended because of toxicities
• Rapid relapse after abrupt discontinuation of
cyclosporine

37. Contraindications
• Concomitant PUVA or UVB, methotrexate or other
immunosuppressive agents, coal tar, history of[200 PUVA
• treatments or radiation therapy
• Abnormal renal function
• Uncontrolled hypertension
• Malignancy
• Hypersensitivity to cyclosporine
• Avoid live vaccinations
• Caution with major infection and poorly controlled diabetes

38. Toxicity
• Renal impairment
Acute
Chronic
• Hypertension
• Malignancies
• Lymphoproliferative
• Headache, tremor, paresthesia
• Hypertrichosis
• Gingival hyperplasia
• Worsening acne
• Nausea/vomiting/diarrhea
•
•
•
•
•
•
•
•
•
Myalgias
Flu-like symptoms
Lethargy
Hypertriglyceridemia
Hypomagnesemia
Hyperkalemia
Hyperbilirubinemia
Increased risk of infection
May increase risk of cancer

39. Drug interactions
• Inducers/inhibitors of cytochrome P450 3A4
• Cyclosporine may reduce clearance of digoxin, colchicine,
prednisolone, statins (increased risk of rhabdomyolysis)
• Potassium-sparing diuretics cause hyperkalemia
• Thiazide diuretics increase nephrotoxicity
• Killed vaccines may have decreased efficacy
• Live vaccination is contraindicated
• Grapefruit juice

40. Baseline monitoring
• History and physical examination
• Blood pressure 2
• BUN and Cr 2
• Urinalysis
• Consider PPD
• LFTs, CBC count, lipid profile, magnesium, uric acid, and potassium
• Pregnancy test if indicated
Ongoing monitoring
• Every other week during initial 3 mo, thereafter at 1-mo intervals: blood
pressure, BUN, and Cr
• Monthly CBC count, LFTs, lipid profile, magnesium, uric acid, and
potassium
• Pregnancy testing if indicated

41. Pregnancy: category C
• appears not to be teratogenic in patients with transplantation
Nursing: mothers receiving cyclosporine should not breast-feed
Pediatric use: transplantation recipients as young as 1 y have
been treated with no unusual adverse events; although
• safety and efficacy of cyclosporine for children <18 y with
psoriasis has not been established
• may be considered in severe psoriasis
Psoriatic arthritis: effective

42. RETINOIDS(ACITRETIN)
Indication: FDA approved for adults with severe plaque type
psoriasis
• In patients with pustular psoriasis, rapid and impressive
responses seen with acitretin (J Dermatol 1999)
• Because of a lack of significant immunosuppression, acitretin
is generally considered effective and the treatment of choice in
HIV-positive patients with severe psoriasis(Arch Dermatol
1997)
Dosing: 10-50 mg/d given as a single dose

43. Results: monotherapy slow onset of action
• Efficacy rates when used in combination with phototherapy
are higher
• Combination with UVB or PUVA determined that
combination enhances efficacy and limits the treatment
frequency, duration, and cumulative doses(J Am Acad
Dermatol 2001)
• The preferred schedule is acitretin monotherapy for 2 weeks
followed by the addition of phototherapy(Arch Dermatol
1990)
• Anticancer potential of oral retinoids may also add to their
safety(J Am Acad Dermatol 2003)

44. Contraindications
• Potent teratogen
• Severely impaired liver or kidney function
• Chronic abnormally elevated blood lipid values
Drug interactions: concomitant use with MTX and tetracyclines
should be avoided
Baseline monitoring
• History and physical examination
• Lipid profile, CBC count, LFTs, RFT
• Pregnancy test if indicated

45. Ongoing monitoring
• LFTs, lipid profile at 2-wk intervals for the first 8 wk, then
every 6-12 wk
• CBC count, renal function tests every 3 mo
• Pregnancy test if indicated
Pregnancy: category X
Nursing: mothers receiving acitretin should not breast-feed
Pediatric use: safety and efficacy of acitretin in children with
psoriasis is not established

46. SECOND TIER SYSTEMIC
AGENTS
1. Azathioprine – D/t absence of data from controlled trials, it is
best to conclude that there is no good evidence that
azathioprine is an effective treatment for psoriasis
2. Fumaric acid esters- Several welldesigned randomized studies
of fumarates demonstrate mean PASI improvement rates of
between 50% and 80% after 12 to 16 weeks of treatment
(BJD1998)
• S/E – GI, flushing, lymphopenia
3. Hydroxyurea- may be a valuable reserve drug for pts needing
systemic treatment and who are resistant to MTX or develop
side effects ( BJD 1989)
4. Leflunomide – may be used in pt of psoriasis with arthiritis
(Arthritis Rheum 2004)

47. 5. Mycophenolate mofetil - has place in the therapy of severe
psoriasis is probably in combination with ciclosporin as a
ciclosporin sparing agent(Clin Exp Dermatol 2001)
6. Systemic glucocorticosteroids - Systemic steroids should not
be used in the routine care of psoriasis
• They do have a role in the management of persistent,
otherwise uncontrollable erythroderma that is causing
metabolic complications
• Fulminating generalized pustular psoriasis of the von
Zumbusch type if other drugs are contraindicated or
ineffective
• Psoriatic arthropathy is not an indication per se, but steroids
may occasionally be needed, and in high dosage to control
hyperacute polyarthritis (Br J Dermatol 1969)

48. OTHERS
• 6- Thioguanine
• Tacrolimus & Pimecrolimus
• Cytokines
• Protein kinase C inhibitor
• Zidovudine
• Somatostatin
• Liarazole
• Gluten free diet
• Liarazole
• Photodynamic therapy
• Lasers

49. UVB PHOTOTHERAPY
Indication:
• Generalized psoriasis (including guttate and seborrhoeic)
unresponsive to topicals
• little value in psoriatic erythroderma and generalized pustular
psoriasis, and may aggravate these forms of the disease
MOA:
•
•
•
•
locally immunosuppressive
switch from a T-helper (Th) 1 to a Th 2 phenotype
inhibition of both epidermal hyperproliferation and angiogenesis
Selective reduction in T lymphocytes within psoriatic skin via
apoptosis (JAAD 2003)

50. Dosing:
BB: Initial dosing according to skin type (20-60 mJ/cm2) or
MED (50% of MED)
• Subsequent dosage increase by 5-30 mJ/cm2 or #25% of initial
MED
NB: Initial dosing according to skin type (130-400 mJ/cm2) or
MED (50% of MED)
• Subsequent dosage increase by 15-65 mJ/cm2 or #10% of
initial MED
Efficacy : NBUVB is not only more effective than BB but also
lead to rapid clearance of lesions(Acta Derm Venereol 1989)

51. Contraindications: Patients with known LE or XP
Caution should be exercised in:
• Pts with skin types I and II who tend to burn easily
• those with history of arsenic intake or previous treatment with
ionizing radiation therapy
• those with history of melanoma or multiple NMSC
Toxicity: Acute: erythema, pruritus, burning, blister( NBUVB)
Long term:
– Photoaging, lentigines, telangiectasias, cataract
– Theoretical risk of photocarcinogenesis
– However numerous studies have failed to show such an effect in
patients with psoriasis after UVB therapy(Int J Dermatol 2005)
– Advise use of protective goggles and genital shields during treatment

52. Pregnancy: not a contraindication
• NB-UVB therapy has been used successfully in the t/t of
psoriasis in pregnancy and should be considered first-line
therapy in pregnant patients with plaque and guttate psoriasis
who need a systemic t/t (Arch Dermatol 1998)
• Neither BB-UVB nor NB-UVB therapy are known to have any
teratogenic effects (J Am Acad Dermatol 2006)
Pediatric use: shown to be effective and well tolerated in limited
number of studies (Pediatr Dermatol 1996)
• Although there are no studies documenting the long-term
safety of UVB phototherapy
• may be used with caution in individuals aged <18 y

53. UVB COMBINATION THERAPY
Combination UVB with topical therapies
• Emollients increase transmission of UV radiation by altering
optical properties of psoriatic skin lesions and improving
therapeutic efficacy (Arch Dermatol 1979)
• Topical CS results are unclear (Arch Dermatol 1991)
• Calcipotriol conflicting reports(J Invest Dermatol 2003)
• Goeckerman and Ingram regimens - less popular in recent
years
• Combination of tar and UVB does not increase incidence of
NMSC over UVB alone (J Am Acad Dermatol 1983)

54. Combination UVB with traditional systemic therapies
• Methotrexate with UVB therapy has shown potential value
because of the synergistic effects of these two therapies
(J Am Acad Dermatol 1991)
• Retinoids with UVB have been extensively studied and
accelerate the response to phototherapy, reducing the
cumulative dosage of UVB and the dose of acitretin required
to achieve psoriasis clearance (Arch Dermatol 1990)

55. TARGETED PHOTOTHERAPY
• Excimer lasers selectively target affected lesions of psoriasis
while leaving unaffected skin untreated
• Advantage treating only involved skin so less S/E not limited
by the MED, which renders this mode of UV therapy more
efficacious when supra-erythemogenic doses are used
(Lancet 1997)
Efficacy : highly effective, can be used for resistant localised
psoriasis such as scalp and palmoplantar psoriasis
(Arch Dermatol 2000)

56. PUVA
PHOTOCHEMOTHERAPY
MOA – UVA irradiation has effects on epidermal keratinocytes
and Langerhans cells (similar to UVB irradiation)
• But because it readily penetrates into the dermis, there are also
effects on dermal cells including granulocytes and T
lymphocytes (J Investig Dermatol Symp Proc 1999)
• Psoralen intercalates between DNA base pairs and, on
exposure to UVA, forms psoralen DNA cross-links that
prevent DNA replication
• Induces ROS formation that leads to cell membrane and
mitochondrial membrane damage and eventual death of APC

57. Dosing: 8-MOP0.4-0.6 mg/kg, taken 1-2 h before exposure to
UVA
• UV protective eye wear should be worn when outdoors for
12hr postingestion
• Treatment 2-3/wk
Results:
• 89% Clearing with average of 25 treatments in US and 20
treatments in Europe (Lancet 1981)
• 11.6 wk to Clear in US studies compared with 5.3 wk to clear
in European studies (J Invest Dermatol 1977)

58. Toxicity:
Acute:
–
–
–
–
–
–
Nausea and vomiting are common
Dizziness and headache are rare
Erythema: peaks at 48-96 h
Pruritus
Tanning: starts 1 wk after PUVA
Blisters, photo-onycholysis, melanonychia
Chronic:
– Photocarcinogenesis (SCC, BCC, and possible melanoma)
– Increased risk of photocarcinogenesis in Caucasians with skin
types I-III after 200 treatments; this risk not present for nonCaucasians
– Photoaging and lentigines are common, especially in patients of
skin types I-III and are cumulative UVA dose dependent

59. Pregnancy: Category C
Nursing: C/I for period of 24 h after ingesting psoralen
Pediatric use: No studies; may be used with caution in individuals
aged < 18 y (J Pediatr 1996)
Contraindications : same as that for phototherapy plus pregnancy,
lactation and severe liver disease

60. Combination of PUVA with other therapies
• Topical CS – unclear effects
• Combination of topical calcipotriol with PUVA leads to a
decrease in duration of PUVA therapy along with an improved
clinical response (J Dermatolog Treat 2004 )
• Combination of oral retinoids with PUVA is more effective
compared with monotherapy with either acitretin or PUVA
alone144-146 (Br J Dermatol 1989)
• Because patients who have previously received PUVA
treatment have an increased risk for developing SCC when
subsequently treated with cyclosporine, this combination
should be avoided (Lancet 2001)
• PUVA with MTX - safety questioned

61. Topical psoralen plus ultraviolet A
Indications:
• Topical PUVA for adults with psoriasis of palms and soles
• Bath PUVA for adults and children with generalized psoriasis
Dosing:
• Topical -Use 0.1% 8-methoxypsoralen in emollient and treat
2-3 /wk
• Apply 30 min before UVA
• Start at 0.25-0.5 J/cm2, increase by 0.25-0.5 J/cm2
• Bath -50 mg of 8-Methoxypsoralen in 100 L of water, 20-30
min pre-exposure

62. Biological therapies
Biologicals use should be restricted to:
(i) patients with severe disease defi ned by a PASI score of 10 or
more (or BSA of 10% or greater where PASI is not applicable)
and DLQI of greater than 10
(ii) who have failed to respond to, or who have a
contraindication to, or who are intolerant to other systemic
therapies such as ciclosporin and methotr exate (Br J Dermatol
2009)
Although there are few exceptions where biologicals can be
considered earlier

63. • At present, there are 5 biological agents licensed for treatment of
psoriasis vulgaris
(i) etanercept, a fully human soluble p75 TNF-α receptor fusion
protein
(ii) infliximab, a chimeric human-immune antibody to TNF-α
(iii) adalimumab, a fully human recombinant antibody to TNF-α
(iv) ustekinumab, a fully human recombinant antibody to the p40
component of IL-12/IL-23
(v) alefacept, a fusion protein of lymphocyte function associated
antigen-3 and IgG that inhibits T-cell activation

64. • Infliximab is administered by i.v. infusion while the others are
administered by s.c. injection
• For stable disease, particularly if not too severe (e.g. PASI >10
but <20), etanercept or adalimumab are often fi rst options
• For patients requiring rapid disease control, adalimumab or
infliximab may be considered first choice due to early onset of
action.
• For patients with unstable or generalized pustular psoriasis,
limited evidence indicates that infliximab is effective and may
be considered first choice amongst the biologics (Lancet 2007)

65. • Equally, it appears to be the most active agent for severe nail
disease including acropustulosis of Hallopeau
• For patients who do not respond to a TNF-α antagonist (either
primary or secondary failure), a second TNF-α antagonist may
be considered
• Ustekinumab should be reserved for use as a second-line
biological agent (Lancet 2005)

66. General recommendations for TNF inhibitors
• Contraindicated in patients with active, serious infections
• Tuberculosis testing (PPD) should be performed on all patients
who will be treated with TNF inhibitors
• live vaccines; biologically inactive or recombinant vaccines
may be considered, although the immune response of these
vaccines could be compromised
• Because there is an association between anti-TNF therapy and
demyelinating diseases (ie, MS) TNF inhibitors should not be
used in patients with MS or other demyelinating diseases

67. • first-degree relatives of patients with MS have an increased
risk of developing MS, with a sibling relative risk of between
18 and 36, evidence strongly suggesting that TNF inhibitors
should not be used in first-degree relatives of patients with MS
• Caution should be used when considering TNF inhibitor use in
patients with CHF; it is recommended that patients with
NYHA class III or IV CHF avoid all use of TNF inhibitors
• Patients with class I or II CHF undergo echocardiogram
testing; if the EF < 50%, then TNF inhibitor treatment should
potentially be avoided
• Patients should be screened for hepatitis B infection
(Best Pract Res 2006)

68. Dosing
Alefacept: 15 mg every wk given as an i.m. injection for 12 wk,
with a 12-wk follow-up nontreatment period
Adalimumab: 80 mg the first wk, 40 mg the second wk, followed
by 40 mg every other wk given s.c.
Etanercept: 50 mg twice/wk given s.c. for 3 mo followed by 50
mg once/wk
Infliximab: 5 mg/kg dose infusion schedule at wk 0, 2, and 6 and
then every 6-8 wk; dose and interval of infusions may be
adjusted as needed

69. Cost of therapy for 12-weeks
Methotrexate
15 mg/week
Rs 370
Acitretin
1 mg/kg/day
Rs 5040
Cyclosporine
50 mg BD
Rs 8050
PUVA
Rs. 3600
PUVAsol
Rs. 1800
Etanercept
50mg twice weekly
Rs 4 lakh
Infliximab
5 mg/kg 3 doses
Rs 3 lakh

78. THANKS