Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis
ABSTRACT To assess the efficacy and safety of a 24-week course of efalizumab.
Phase 3, randomized, double-blind, parallel-group, placebo-controlled 12-week study followed by a 12-week open-label study.
Outpatient dermatology clinics. Patients A total of 556 patients with moderate to severe chronic plaque psoriasis who were seeing an outpatient dermatologist were included in the study. Intervention For weeks 1 to 12, the 556 patients were randomized to receive 1 mg/kg of efalizumab weekly or placebo subcutaneously. For weeks 13 to 24, 516 of these patients received 1 mg/kg of efalizumab weekly.
Proportion of patients with a 75% or greater improvement in Psoriasis Area and Severity Index (PASI-75), a 50% or greater improvement in PASI (PASI-50), static Physician's Global Assessment (sPGA) rating of minimal or clear, and improvements in Dermatology Life Quality Index (DLQI), itching scale, and Psoriasis Symptom Assessment (PSA) frequency and severity scores at weeks 12 and 24. Safety was evaluated by reviewing adverse events, laboratory parameters, vital signs, and anti-efalizumab antibodies.
At week 12, 26.6% of efalizumab-treated patients achieved PASI-75 and 58.5% achieved PASI-50. After 24 weeks of continuous efalizumab therapy, PASI responses increased: 43.8% of patients achieved PASI-75 and 66.6% achieved PASI-50. The percentage of patients who achieved an sPGA rating of minimal or clear increased from 25.7% to 35.9%. The mean percentage of improvement in all patient-reported outcomes (DLQI, itching scale, and PSA frequency and severity scores) at week 12 was maintained at week 24 (DLQI, 49.2%; itching scale, 42.2%; PSA frequency, 47.6%; PSA severity, 47.3%). There was a decline in overall reported adverse events from weeks 1 to 12 (80.4%) to weeks 13 to 24 (63.2%) without evidence of cumulative toxic effects. Conclusion Extending efalizumab treatment from 12 to 24 weeks leads to improved efficacy and maintenance of quality of life with no evidence of cumulative toxic effects noted in patients with moderate to severe chronic plaque psoriasis.
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ABSTRACT: Efalizumab is an mAb directed against CD11a, a molecule involved in T-cell activation and extravasation from blood into tissue. Ten patients with severe atopic dermatitis were treated with efalizumab for 84 days, and peripheral blood mononuclear cells were analyzed for expression of activation and adhesion markers. Efalizumab treatment led to decreases in CD11a mean fluorescence intensity (MFI) on naive, central memory, and effector memory CD4+ and CD8+ T cell subsets. MFI for CD18 was decreased in both CD4+ and CD8+ T cells. Percentages of cells positive for cutaneous lymphocyte antigen (CLA) were increased fourfold in all CD4+ and CD8+ T cell subsets. Increases in the percentages of CD4+ and CD8+ T cells expressing beta7 and CD49d were also observed. No significant changes were observed in the percentages of CD4+ and CD8+ T cells that produced either IFN-gamma or IL-4. In summary, efalizumab treatment resulted in (i) decreases in CD11a and CD18 expression in all circulating T-cell subsets and (ii) increases in the percentages of blood T cells expressing tissue homing markers (CLA, beta7, CD49d). These data suggest that blockade of T-cell extravasation into tissue is the major pathway by which efalizumab leads to improvement in cutaneous inflammation.Journal of Investigative Dermatology 06/2008; 128(5):1173-81. DOI:10.1038/sj.jid.5701169 · 6.37 Impact Factor
Article: Biologicals in psoriasis[Show abstract] [Hide abstract]
ABSTRACT: During the recent years, a new class of therapeutic agents has been introduced for the treatment of psoriasis and psoriatic arthritis. These agents target different inflammatory mediators involved in the pathogenesis of disease. The focus of this article is on the mechanism of action, side effect profile and dosing of the agents currently in use today for the treatment of psoriasis
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ABSTRACT: Özet Psoriasis, s›k görülen, çou kez yaflam boyunca süren ve genellikle tedaviyle yok edilemeyen bir hastal›kt›r. Bu durum, hastalar›n yaflam boyunca tedavi edilmesini ve özellikle fliddetli hastal›¤› olan hastalarda, önemli yan etkileri olan ilaçlar›n uzun süreli kulla- n›lmas›n› gerektirir. Bu derlemenin amac›, dermatoji uzman›na, orta ve fliddetli psoriasisi olan bir hastayla karfl›laflt›¤›nda hangi yön- temi seçmesi gerektiiyle ilgili rehberlik edebilmektir. Bu balamda fototerapi, geleneksel ve biyolojik tedavi ajanlar›, avantaj ve dezavantajlar›, izlemde dikkat edilmesi gereken yönleriyle tart›fl›lacakt›r. (Türk Dermatoloji Dergisi 2007; 1: 8-14) Anahtar kelimeler: Psoriasis, tedavi, metotreksat, fototerapi, siklosporin, asitretin, biyolojik ajan Summary Psoriasis is a chronic disease with no cure. Patients with moderate to severe psoriasis require lifelong treatment with systemic mo- dalities, which have severe side effects. This review aims to guide the dermatologist in the selection of the appropriate modality for treating patients with moderate to severe psoriasis. Phototherapy, traditional medications and biologics are discussed, with a spe- cial emphasis on the advantages and disadvantages of each modality. (Turkish Journal of Dermatology 2007; 1: 8-14)