Efalizumab: results of a 3-year continuous dosing study for the long-term control of psoriasis

BACKGROUND: Efalizumab, a T-cell-targeted, recombinant, humanized, monoclonal IgG1 antibody, inhibits key T-cell-mediated steps in the pathogenesis of psoriasis. Efalizumab is approved for the treatment of moderate-to-severe chronic plaque psoriasis in adults in more than 50 countries. OBJECTIVES: To evaluate the efficacy and safety of long-term, continuous efalizumab therapy in patients with psoriasis. METHODS: This open-label, multicentre phase III study enrolled 339 patients with moderate-to-severe chronic plaque psoriasis. During the initial 3-month phase, patients received subcutaneous efalizumab 2 mg kg(−1) weekly with randomization to receive concomitant fluocinolone acetonide or placebo ointment during month 3. The second phase was a long-term observational period; patients achieving a ≥ 50% improvement in the Psoriasis Area and Severity Index (PASI) score were eligible to receive efalizumab 1 mg kg(−1) weekly for up to 33 months. The final 3-month treatment period was an optional transition period for patients who completed the 33-month segment before efalizumab became commercially available. RESULTS: After 3 months, 41·3% of patients achieved a ≥ 75% improvement in PASI (PASI-75) and 13·0% achieved a ≥ 90% improvement (PASI-90). Continued improvement was observed: 45·4% and 24·5% achieved PASI-75 and PASI-90, respectively, at the end of the observational phase. The safety profile was stable, with no new or no increase in common events over 36 months of treatment. CONCLUSIONS: This was the longest continuous study using a biologic therapy for psoriasis. Clinical benefit of efalizumab improved over the first 18 months and was maintained during 36 months of continuous therapy. Long-term efalizumab therapy is appropriate for many patients with plaque psoriasis. CONFLICTS OF INTEREST: C.L. with 3M Pharmaceuticals, Abbott, Allergan, Altana, Amgen, Astellas-Biogen, Bristol Myers, Centocor, CombinatoRx, Fujisawa Healthcare, Galderma, Genentech, Merck Serono International SA, Schering Plough, RTL, Vitae and Warner Chilcott; A.M. with 3M Pharmaceuticals, Abbott, Allergan, Allermed, Amgen, Astralis, Berlex, Biogen Idec, Celgene, Centocor, Cephalon, Collagenex Pharmaceuticals, CombinatoRx, Connetics, Corixa, Dermik Laboratories, Doak Dermatologics, Dow, Ferndale Laboratories, Fujisawa Healthcare, Galderma, Genentech, Genzyme, GlaxoSmithKline, Ligand Pharmaceuticals, Medicis, MedImmune, Novartis Pharmaceuticals, Otsuka Pharmaceutical, Protein Design Labs, QLT USA, Regeneration Pharma AG, Roche, Merck Serono International SA, Sinclair, Synta Pharma, Thermosurgery, Vertex, Warner Chilcott, Wyeth, XOMA and Zars; T.H. with Genentech; A.B.G. with Abbott, Actelion, Almirall, Amgen, Beiersdorf, Biogen Idec, Bristol Myers Squibb, Can-Fite, Celera, Celgene, Centocor, DermiPsor, Eisai, Genentech, Immune Control, Incyte, Kemia, Medacorp, Medarex, Novo Nordisk, Pharmacare, Roche, RxClinical, Sankyo, Schering Plough, TEVA, UCB, Warner Chilcott and Wyeth. All income derived from these sources goes to her employer. I.C. and B.X. are employees and stockholders of Genentech.