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: BACKGROUND: Multiple metrics evaluate the efficacy of psoriasis treatment, but interestingly, the correlation between the mostly widely used clinical trial efficacy end point, the physician-rendered Psoriasis Area Severity Index PASI score and, the most widely used quality of life metric, the Dermatology Life Quality Index DLQI, is not always high. OBJECTIVE: To perform a systematic review to determine PASI to DLQI correlation. METHODS: RCTs of biological agents for the treatment of moderate-to-severe psoriasis were reviewed in accordance with PRISMA guidelines. The mean percentage PASI improvement and change in mean DLQI values were recorded and compared for treatment groups from baseline to 10-16 weeks of therapy. RESULTS: A search of the literature yielded 155 sources, of which 13 RCTs met inclusion and exclusion criteria. Percentage of PASI improvement from baseline correlates with DLQI changes with an r(2) value of 0.80 from baseline through weeks 10-16. When grouped by mean percentage reduction in PASI, agents demonstrating >75% mean reduction in PASI demonstrated a mean DLQI improvement over agents that achieved <75%-50% mean reduction in PASI or <50% mean reduction in PASI [minimal clinically important difference (MCID) 3.2]. In addition, a reduction in mean PASI of at least 75%, predicted a mean movement from DLQI band 3 to DLQI band 1, in all nine treatment arms demonstrating such efficacy. CONCLUSIONS: Mean PASI and DLQI correlate predictably in patients with chronic moderate-to-severe plaque psoriasis undergoing treatment with biological agents. A reduction in PASI of at least 75% can translate to significant quality-of-life improvement in patients treated with these therapies.Journal of the European Academy of Dermatology and Venereology 02/2013; · 2.69 Impact Factor
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ABSTRACT: The recommendations in clinical guidelines are based on clinical trial findings and expert opinion. The influence of drug companies on these two factors is illustrated with two examples. A judicially ordered expert review revealed that the market authorization holder (MAH) of gabapentin manipulated study data. Gabapentin was, therefore, chosen as an example for this article to analyze whether manipulated data serve as a basis for recommendations in German clinical guidelines. A search was carried out for manipulated publications on gabapentin that found their way into guidelines published by the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). To analyze the possible effects of financial ties between guideline authors and drug companies, the S3 guideline on the treatment of psoriasis vulgaris with efalizumab was compared with guidelines whose authors had no conflicts of interest. One of the authors of this article had noted variable prescribing practices for psoriasis among dermatologists while carrying out an economic assessment for a German state Association of Statutory Health Insurance Physicians. The data that had been manipulated by the MAH of gabapentin served as a basis for recommendations to prescribe gabapentin in guidelines that were published by the AWMF. Efalizumab was judged more favorably in the S3 guideline than in a guideline issued by the National Institute of Health and Care Excellence: for example, the evidence for it was judged as good, the use of efalizumab for induction and combination therapy in psoriasis vulgaris was recommended, and efalizumab was said to improve patients' health-related quality of life. Public access to all trial data must be ensured so that independent evaluations are possible. We take the view that the responsibility for creating guidelines should be borne by authors and organizations that do not have any conflicts of interest.Deutsches Ärzteblatt International 09/2013; 110(35-36):575-83. · 3.54 Impact Factor
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ABSTRACT: To perform a systematic review and meta-analysis of randomized controlled trials (RCT’s) reporting efficacy of systematic treatments approved for moderate-to-severe psoriasis by means of the Psoriasis Area And severity Index (PASI). I identified relevant articles by systematic electronic searches (Cochrane Library, Medline,). Efficacy was defined as proportion of participants with > 75% decrease in PASI (PASI-75) at primary efficacy measurement (week8-16). PASI-75 response rates of double-blind placebo-controlled trials were summarized as risk differences (RDs) and pooled using random effect models. Tolerability was assessed from rates of withdrawals and adverse events. Twenty-one RCT’s totaling 7877 patients were analyzed qualitatively. Sixteen double-blind placebo-controlled trials were eligible for meta-analysis. Infliximab was significantly superior to all other interventions (RD 77%, 95% confidence interval (CI) 72-81%). Adalimumab (RD 64%, 95% CI 61-68%) was superior to efalizumab (RD 24%, 95% CI 19-30%). Etanercept 50 mg twice weekly (RD 44%, 95% CI 40-48%) and etanercept 25 mg twice weekly (RD 30%, 95% CI 25-35%). Rates of withdrawals due to adverse events were highest for methotrexate and fumaric acid esters. There are considerable differences in efficacy between systemic biologic therapies which are approved for the treatment of moderate-to-severe psoriasis. Infliximab is most efficacious, followed by adalimumab. Patients receiving infliximab have an excess chance of 77% over placebo to achieve PASI-75 response. Published evidence questions regulatory guidelines that recommend biologics as second-line therapy for moderate-to-severe plaque psoriasis.Journal of Taibah University Medical Sciences. 01/2013;