Efficacy and Safety Observed During 24 Weeks of Efalizumab Therapy in Patients with Moderate to Severe Plaque Psoriasis
Baylor University Medical Center, Dallas, TX, USA. Archives of Dermatology
(Impact Factor: 4.79).
02/2005; 141(1):31-8. DOI: 10.1001/archderm.141.1.31
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.
Available from: Danúbia da Cunha Sá-Caputo
- "The Psoriasis Area and Severity Index (PASI) is one of the most frequently used instruments to evaluate the severity of the disease and its response to different treatments, and its use is based on the extension and severity of the impact on the skin's surface. Relevant aspects of psoriasis that affect the person with this disease are evaluated using a variety of instruments , including the Psoriasis Disability Index (PDI), Dermatology Quality of Life Index (DLQI), the Psoriasis Symptom Assessment, and the Itching Scale. The Physician Global Assessment is a tool to evaluate the psoriatic plaques. "
Available from: Craig I Coleman
- "Five RCTs evaluated the anti-T cell agents, with one alefacept study , and two efalizumab studies [30, 32] reporting results using FDA-approved doses. Seven RCTs evaluated the anti-TNF agents, with three infliximab studies [37, 38, 40], two adalimumab studies [41–43], and one etanercept study  reporting results using FDA-approved doses. "
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The objective of this review was to conduct a systematic review with meta-analysis and Bayesian mixed treatment comparisons (MTC) evaluating the impact of biologics on non-Psoriasis Area and Severity Index (PASI) health outcomes in patients with moderate-to-severe plaque psoriasis.
MEDLINE and Cochrane Central Register of Controlled Trials were searched from 1966 to May 2009. Citations were screened for randomized, controlled trials of biologics versus either placebo or each other in adults with moderate-to-severe plaque psoriasis and reported any of several outcomes. Traditional and Bayesian MTC meta-analyses were conducted for each endpoint using either a random- or fixed-effect model where appropriate.
Thirty-eight studies met eligibility criteria. All biologics showed significant improvement in achieving a good response on the static physician’s global assessment (PGA) versus placebo while, in the MTC, differences were noted between individual drugs. In achieving a good response on the dynamic PGA, all biologics showed significant improvements over placebo, while the MTC showed significant improvements with the anti-interleukins versus anti-T cells. Relative to placebo, antitumor necrosis factor (TNF) agents and anti-interleukins showed significant improvements in the Dermatology Life Quality Index (DLQI). Compared with placebo, the anti-TNF agents showed significant improvements in both 36-item Medical Outcomes Study Short-Form General Health Survey (SF-36) mental and physical component scores, while anti-T cell agents showed no improvements. The MTC showed no differences between any biologics for either the DLQI or SF-36.
Individual biologics and classes showed consistent benefits across non-PASI health outcomes in patients with moderate-to-severe plaque psoriasis while MTC meta-analyses suggested that some differences exist.
Available from: PubMed Central
- "The long-term continuous efalizumab therapy not only sustained the efficacy without increasing cumulative and organ toxicity, but also resulted in additional clinical improvement, as demonstrated in two other clinical trials. In-fact in a phase III randomized double-blind placebo-controlled trial followed by an open-label study, 26.6% and 58.5% of patients, achieving PASI-75 and PASI-50 after 12 weeks therapy with the 1 mg/kg dose, rose to 43% and 66% after 24 weeks of continued treatment, respectively (Menter et al 2005). In a consecutive open-label trial, the PASI improvement was maintained throughout the 30-month treatment period (Gottlieb et al 2006). "
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ABSTRACT: Chronic plaque psoriasis affects more than 2% of world population, has a chronic recurrent behavior, gives a heavy burden to the patients' quality of life, and hence remains a huge medical and social problem. The clinical results of conventional therapies of psoriasis are not satisfactory. According to the current knowledge of the molecular and cellular basis of psoriasis, it is defined as an immune-mediated chronic inflammatory and hyperproliferative skin disease. A new generation of biological drugs, targeting molecules and cells involved into perturbed pro-inflammatory immune response in the psoriatic skin and joints, has been recently designed and applied clinically. These biological agents are bioengineered proteins such as chimeric and humanized antibodies and fusion proteins. In particular, they comprise the antitumor necrosis factor-alpha agents etanercept, infliximab, and adalimumab, with clinical efficacy in both moderate-severe psoriasis and psoriatic arthritis, and the anti-CD11a efalizumab with selective therapeutic action exclusively in the skin. Here, we overview recent findings on the molecular pathways relevant to the inflammatory response in psoriasis and present our clinical experience with the drugs currently employed in the dermatologic manifestations, namely etanercept, infliximab, and efalizumab. The growing body of clinical data on the efficacy and safety of antipsoriasis biological drugs is reviewed as well. Particular focus is given to long-term safety concerns and feasibility of combined therapeutic protocols to ameliorate clinical results.
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