Efalizumab for Patients With Moderate to Severe Plaque Psoriasis

Abstract

Context Because T-cell interactions are involved in the pathophysiology of psoriasis, therapy with a T-cell modulator may have beneficial effects on psoriasis severity and health-related quality of life (HRQL). Objective To assess the efficacy and safety of efalizumab, a T-cell modulator, in patients with plaque psoriasis. Design, Setting, and Patients Phase 3 randomized, double-blind, parallelgroup, placebo-controlled trial involving 556 adult patients with stable, moderate to severe plaque psoriasis and conducted at 30 study centers in the United States and Canada between January and July 2002. Interventions Patients were randomly assigned in a 2:1 ratio to receive 12 weekly doses of subcutaneous efalizumab, 1 mg/kg (n=369), or placebo equivalent (n=187). Main Outcome Measures At least 75% improvement on the Psoriasis Area and Severity Index (PASI-75); improvement on the overall Dermatology Life Quality Index (DLQI), Itching Visual Analog Scale (VAS), and Psoriasis Symptom Assessment (PSA) at week 12 vs baseline. Results Efalizumab-treated patients experienced significantly greater improvement on all end points than placebo-treated patients. Twenty-seven percent of efalizumabtreated patients achieved PASI-75 vs 4% of the placebo group (PϽ.001). Efalizumabtreated patients exhibited significantly greater mean percentage improvement than placebo-treated patients on the overall DLQI (47% vs 14%; PϽ.001), Itching VAS (38% vs −0.2%; PϽ.001), and PSA frequency and severity subscales (48% vs 18% and 47% vs 17%, respectively; PϽ.001 for both) at the first assessment point. Efalizumab was safe and well tolerated, with primarily mild to moderate adverse events. Conclusion In this 12-week study, efalizumab resulted in significant improvements in clinical end points, including physician-assessed and dermatology-specific patientreported HRQL measures, in patients with moderate to severe plaque psoriasis.

AL-57, a ligand-mimetic antibody to integrin LFA-1, reveals chemokine-induced affinity up-regulation in lymphocytes

“…For comparison, we used MHM24, a conventional activation-insensitive mAb to the ␣ L I domain. MHM24 is a mouse mAb to human LFA-1 (33) that was humanized as efalizumab (Raptiva) and is used for the treatment of psoriasis patients (34)(35)(36). To exclude bivalent interactions, mAbs were immobilized on CM-5 sensor chips, and monovalent I domains were injected as analytes.…”

Efficacy and safety of biologics in the treatment of moderate to severe psoriasis: a comprehensive meta-analysis of randomized controlled trials

“…20,674 articles were found, of which 20,592 were excluded, resulting in 82 articles in which 41 clinical trials comparing biologics with placebo (six adalimumab 17,18,19,20,21,22,23,24,25,26,27 , three alefacept 28,29,30,31,32,33,34,35,36,37 , one briakinumab 38,39 , one certolizumab 40 , seven efalizumab 41,42,43,44,45,46,47,48,49,50,51 , eight etanercept 52,53,54,55,56,57,58,59,60,61,62,63,64 , one golimumab 65,66 , eight infliximab …”

Tolerance--Is It Worth It?

“…The third target, efalizumab, is a humanized anti-LFA-1 (CD11a/CD18) monoclonal antibody that was approved for the treatment of psoriasis (Dedrick et al 2002;Stern 2003), and has been effective at reducing the severity of the disease in moderate to severe psoriasis (Gordon et al 2003;Lebwohl et al 2003). The antibody blocks the cell-adhesion molecule LFA-1 from binding to its ligand ICAM-1.…”