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: 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. 12/2013;
Article: Efalizumab[Show abstract] [Hide abstract]
ABSTRACT: Pharmacologic Properties Efalizumab inhibits the interaction of LFA-1 with its ligand, intercellular adhesion molecule-1, thereby interfering with at least three important events in the T-cell-mediated immunopathology of psoriasis (i.e. initial activation, trafficking, and reactivation of T cells). Therapeutic Efficacy The efficacy of efalizumab as monotherapy has been evaluated in adults with chronic moderate-to-severe plaque psoriasis (e.g. baseline psoriasis area severity index [PASI] score ≥12). A 12-week course of subcutaneous efalizumab 1 mg/kg/week (including an initial conditioning dose of 0.7 mg/kg/week) was superior to placebo in reducing physician-assessed disease severity in five randomized, double-blind, multicenter studies. The proportion of patients who achieved a ≥75% improvement in PASI from baseline (PASI 75) at week 12 (primary endpoint in four studies) ranged from 22% to 38.9% with efalizumab versus 2.4–5% with placebo (p < 0.001). Treatment with efalizumab was also more effective than placebo in improving patient-reported outcomes; these included health-related quality of life (HR-QOL), as assessed using dermatologic-specific and generic instruments, and psoriasis-related cutaneous symptoms. Significant improvements in physician- and patient-assessed endpoints were seen after 2–4 weeks’ therapy. In one large study (n = 793), the efficacy of efalizumab in the majority subgroup of 526 subjectively defined ‘high-need’ patients (i.e. those for whom at least two currently available systemic therapies were unsuitable due to lack of efficacy, intolerance, or contraindication) was similar to that in the total study population. Extending the duration of treatment with efalizumab 1 mg/kg/week from 12 to 24 weeks was associated with further reductions in disease severity as well as maintained improvements in patient HR-QOL and other selfreported outcomes. Similarly, additional or maintained improvements in physician-assessed outcomes were observed when treatment with efalizumab 1 mg/kg/week was continued beyond 12 weeks in the noncomparative CONTROL I and II studies; the latter was a large trial in 1255 evaluable patients who had failed to respond to, had a contraindication to, or were intolerant of, other systemic therapies. Efalizumab therapy was effective in reducing disease severity in subgroups of patients with difficult-to-treat forms of plaque psoriasis affecting the scalp, hands/feet, or nails who were enrolled in these studies. The long-term efficacy of efalizumab has been demonstrated in clinical studies in which the drug has been administered continuously (mostly at a maintenance dosage of 1 mg/kg/week) for up to 3 years. Efalizumab is a suppressive therapy intended for continuous administration. Among patients who achieved a PASI 75 response, 86% experienced psoriasis relapse (after a median time of 67 days), and 14% experienced psoriasis rebound (after a median time of 36 days), following abrupt discontinuation of efalizumab (pooled data). Retreatment with a 12-week course of efalizumab was effective in reducing disease severity in patients who previously discontinued treatment (the response rate in terms of the proportion of patients who achieved a ≥50% improvement in PASI from baseline, or attained a dynamic physician’s global assessment rating of good, excellent, or cleared, was ≈56%). Tolerability Weekly subcutaneous injections of efalizumab were generally well tolerated. The most common adverse events in patients treated with efalizumab 1 mg/kg/week (includes an initial conditioning dose of 0.7 mg/kg) in 12-week, double-blind, placebo-controlled trials were mild-to-moderate, acute flu-like symptoms (e.g. headache, chills, nausea, myalgia, and fever) that began within 2 days following the first two injections. Most of these events were self-limiting or could be managed with acetaminophen (paracetamol) or NSAIDs.American Journal of Clinical Dermatology 10(1). · 2.52 Impact Factor
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ABSTRACT: The advent of biologics in dermatologic treatment armentarium has added refreshing dimensions, for it is a major breakthrough. Several agents are now available for use. It is therefore imperative to succinctly comprehend their pharmacokinetics for their apt use. A concerted endeavor has been made to delve on this subject. The major groups of biologics have been covered and include: Drugs acting against TNF-α, Alefacept, Ustekinumab, Rituximab, IVIG and Omalizumab. The relevant pharmacokinetic characteristics have been detailed. Their respective label (approved) and off-label (unapproved) indications have been defined, highlighting their dosage protocol, availability and mode of administration. The evidence level of each indication has also been discussed to apprise the clinician of their current and prospective uses. Individual anti-TNF drugs are not identical in their actions and often one is superior to the other in a particular disease. Hence, the section on anti-TNF agents mentions the literature on each drug separately, and not as a group. The limitations for their use have also been clearly brought out.Indian Journal of Dermatology 09/2014; 59(5):425-41.