This study highlights data from two existing clinical trials to capture PASI 50 and PASI 75 responder rates which represent a common metric used in current psoriasis clinical trials. A review of pharmacokinetics, safety and a discussion of relapse rate establish acitretin as an efficacious, convenient, oral treatment for initial and maintenance therapy of severe psoriasis.
Mechanism of action The efficacy of acitretin in psoriasis is mainly explained by the fact that this compound acts on a pathological epidermis to reduce proliferation and stimulate differentiation.
It also decreases inflammation in the epidermis and dermis by interfering with various cytokines.
However, in contrast to other systemic psoriasis protein intake drugs, psoriasis protein intake is neither cytotoxic nor immunosuppressive. The cellular mechanisms underlying the pharmacological effects of acitretin are not well characterized.
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- Start Page Psoriasis kezelése Psoriasis kezelése A psoriasis kezelési lehetõségei.
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- Efficacy of Acitretin in Severe Psoriasis
Acitretin appears to interfere with the intracellular metabolism of natural retinoids. Pharmacokinetics Acitretin exists in the form of 10mg and 25mg capsules, administered once daily during a meal, since the concomitant intake with food increases the bioavailability of the drug.
After treatment discontinuation, the terminal elimination half-life of acitretin is approximately 50 hours and that of its cis isomer around 90 hours. However, measurable levels of etretinate, have been detected in plasma samples of some patients taking acitretin.
Experimental data indicate that etretinate is formed when acitretin is taken concomitantly with ethanol. This has been confirmed in a clinical study.
The maintenance dose should be based on clinical efficacy and tolerability. The best clinical responses are obtained in localized or generalized Zumbusch type pustular psoriasis and in erythrodermic psoriasis.
Acitretin markedly improves plaque-type psoriasis and complete remission is obtained in around one-third of patients. In some patients, an initial worsening of the disease may be observed with an increase in erythema and in the extent of lesions.
After weeks initial therapy, efficacy can be safely maintained in a long term treatment with acitretin. In study A3, a multicenter Canadian trial, a total of 63 patients 42 men, 21 women with severe psoriasis were enrolled.
PGA evaluations found Study B4 was a multicenter, double-blind trial comparing acitretin and etretinate that was conducted in the four European Nordic countries.
A total of patients received acitretin median daily dose: 40 mg and 41 patients received etretinate median daily dose: Relapse rate The differences in the duration of response between various psoriasis therapies is not well established, since the definitions of relapse used in various clinical studies differ.
In a double-blind study comparing acitretin with etretinate, patients were followed for 6-months after a week treatment course. Contraindications There is an extremely high risk that major fetal abnormalities will occur if pregnancy occurs during treatment with acitretin. Effective contraceptive measures must be used for at least one month before starting treatment, during treatment and for at least 3 years after discontinuation of treatment.
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- Psoriasis kezelése
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This post-therapy contraception period is based on the potential formation of etretinate in presence of alcohol see pharmacology. Adverse events Mucocutaneous reactions Psoriasis protein intake dose-related effects on the skin and mucous membranes are almost always observed during treatment with acitretin.
Dry lips or cheilitis is the earliest and most frequent sign appearing after treatment starts.
Other reactions frequently observed include xerosis of the skin, pruritus, peeling of the palms and soles, epistaxis, conjunctivitis and hair loss. All these reactions are dosedependant and rapidly reversible after drug discontinuation.
Efficacy of Acitretin in Severe Psoriasis
Systemic toxic effects The most common clinical adverse effects include headache, pikkelysömör kezelésének súlyosbodása, myalgia, and fatigue. Skeletal changes after long-term use have been attributed to retinoids. However, a prospective study has failed to document new spurs or other bone changes. Due to its long-term safety, acitretin can be used both as an initial and a maintenance treatment.
References Brindley CJ. Overview of recent clinical pharmacokinetic studies with acitretin Roetretin. Dermatologica 2 Acitretin is converted to etretinate only during concomitant alcohol intake. Br J Dermatol 6 : Dec. A 12 month treatment of severe psoriasis with acitretin: results of a Canadian open multicenter study.
J Am Acad Dermatol 24 4 Apr. A double-blind comparison of acitretin and etretinate in the treatment of severe psoriasis. Results of a Nordic multicentre study.
Acta Derm Venereol 69 1 Relapse rate of severe generalized psoriasis after treatment with acitretin or etretinate. Results the first randomized double-blind multicenter half-year follow-up study. Eur J Dermatol Prolonged treatment with oral retinoids in adults: no influence on the frequency and severity of spinal abnormalities. Br J Dermatol 1 Jan. STL Achives.