Modulating T cell responses for the treatment of psoriasis: a focus on efalizumab

Abstract

An improved understanding regarding the pathophysiology of psoriasis, coupled with advances in molecular research, has prompted the development of targeted biologic treatments for patients with plaque psoriasis. T lymphocytes play an important role in initiating the immune system and the inflammatory responses that result in the development and maintenance of psoriatic plaques. Efalizumab (anti-CD11a, Raptiva™; Genentech, Inc.) is a mAb that targets the T cell adhesion molecule, leukocyte function-associated antigen-1 (LFA-1). By binding to CD11a – the α-subunit of LFA-1 – LFA-1 is prevented from binding with its ligand, intercellular adhesion molecule-1 (ICAM-1). This inhibits various T cell processes believed to be important in the pathogenesis of psoriasis, including T cell activation, T cell adhesion to endothelial cells and T cell migration. Clinical trials demonstrate that efalizumab, given subcutaneously once-weekly, provides clinical benefit, including improved quality of life, in patients with moderate-to-severe plaque psoriasis. Efalizumab is associated with an early onset of action, with improvement noted as early as 14 days. Studies with extended treatment suggest that continuing efalizumab therapy is more beneficial in maintaining and improving responses. Relapse of psoriasis is usually seen within 60 – 70 days after discontinuation of therapy, and rebound in ~ 5% of patients (i.e., flare to > 125% of baseline) is noted. Efalizumab is associated with acute adverse events during the first and second injections, which decrease in incidence with each subsequent injection. Data indicate that efalizumab can be safely administered for extended periods of time. Given the efficacy, early onset of clinical benefit, the safety profile and the convenience of once-weekly subcutaneous home dosing, efalizumab offers an interesting new therapeutic option for the treatment of psoriasis and the potential for improved and potentially safer long-term, continuous ‘maintenance’ therapy.