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: BackgroundTNF-α inhibitors, including infliximab (IFX), can improve disease control of plaque-type psoriasis.Objectives The Real-World Assessment of Long-Term Infliximab Therapy for Psoriasis (REALITY) study evaluated efficacy and safety of maintenance IFX in typical clinical settings.Methods In this prospective, observational, open-label, multicentre study in patients with plaque-type psoriasis, IFX 5 mg/kg was infused at weeks 0, 2, and 6, and every 8 weeks thereafter during a 50-week Treatment Phase. The primary outcome was ≥75% Psoriasis Area and Severity Index (PASI 75) improvement from baseline to week 50. Patients with ≥25% PASI improvement from baseline to the end of the Treatment Phase were potentially eligible to enter a 48-week Extended Treatment Phase. Response maintenance and other efficacy measures were evaluated. Adverse events (AEs) were collected.Results660 patients enrolled. Of 521 efficacy-evaluable Treatment Phase patients (66% male, mean age 46.5 years, mean PASI 18.1), 56.8% achieved PASI 75 at the end of the Treatment Phase. Response was maintained at week 50 by 64.7% (205/317) of patients who achieved PASI 75 at week 14. During Extended Treatment, 66.3% (112/169) of patients attained PASI 75 at week 98; response was maintained at week 98 by 71.6% (101/141) of those who achieved PASI 75 at week 50. IFX was generally well tolerated. During Treatment, 7.6% (50/659) of patients had SAEs. During Extended Treatment, 4.2% (8/193) of patients had SAEs.ConclusionsPASI 75 response was achieved by 56.8% and 66.3% of patients at weeks 50 and 98, respectively. The AE pattern was consistent with previous reports.This article is protected by copyright. All rights reserved.British Journal of Dermatology 03/2014; 171(3). DOI:10.1111/bjd.13004 · 4.10 Impact Factor
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ABSTRACT: Background Multiple biological therapies are approved for the treatment of moderate-to-severe psoriasis.Objectives To assess the short-term efficacy of biological treatments for moderate-to-severe psoriasis via a network meta-analysis that adjusts for reference arm response rates.Methods Fifteen randomized trials of biological treatments for moderate-to-severe psoriasis were identified. Rates of response, assessed as 50%, 75% and 90% reductions in the Psoriasis Area and Severity Index (PASI), were compared using a network meta-analysis. To account for variation across trials, the model was adjusted for placebo responses, the relevance of which was assessed by testing its statistical significance, impact on model fit, and extent to which lack of adjustment confounded the efficacy estimates for biologics.ResultsPsoriasis Area and Severity Index 75 response rates for placebo arms ranged from 1·8% to 18·9%. The probability of achieving a PASI 75 response was 80·5% [95% credible interval (CrI) 74·8-85·7] with infliximab 5 mg kg−1; 72·5% (95% CI 66·1-78·3) with ustekinumab 90 mg; 67·5% (95% CI 60·7-73·9) with ustekinumab 45 mg; 66·2% (95% CI 57·3-73·3) with adalimumab 40 mg; 51·9% (95% CI 45·7-58·4) with etaner-cept 50 mg; and 38·0% (95% CI 31·6-45·1) with etanercept 25 mg. Infliximab had the highest PASI 75 response. Adalimumab and both ustekinumab doses had significantly higher PASI 75 responses than both etanercept doses. There were no significant differences among adalimumab and ustekinumab doses.ConclusionsA model adjusted for reference arm response rates was found to fit clinical trial data significantly better than unadjusted models.British Journal of Dermatology 10/2014; 172(2). DOI:10.1111/bjd.13437 · 4.10 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. DOI:10.4103/0019-5154.139859