Published on February 19, 2014
SEMINAR PRESENTATION PSORIASIS: EVIDENCE BASED TREATMENT Moderator Dr. Deepak K. Mathur
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
• Use can be both intermittent and long-term • Adherence is a major issue, being generally poor in majority of pts
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
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
• 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
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
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 )
• 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)
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)
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
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
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
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
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)
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
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
• 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)
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)
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)
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)
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)
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
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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
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
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)
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)
OTHERS • 6- Thioguanine • Tacrolimus & Pimecrolimus • Cytokines • Protein kinase C inhibitor • Zidovudine • Somatostatin • Liarazole • Gluten free diet • Liarazole • Photodynamic therapy • Lasers
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)
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)
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
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
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)
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)
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)
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
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)
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
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
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
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
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
• 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
• 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)
• 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)
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
• 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)
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
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
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