This is a Phase IIIb/IV, open label, multicentre study of efalizumab (anti cluster of differentiation [CD] 11a recombinant human monoclonal antibody) in participants with moderate to severe plaque psoriasis who have failed to respond to, have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate, and psoralen and ultraviolet A phototherapy (PUVA).

Inclusion Criteria:

• Moderate to severe plaque psoriasis participants who have failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including cyclosporine, methotrexate and PUVA
• Age at least 18 years
• For women of childbearing potential and for men whose partner can become pregnant, use of an acceptable method of contraception to prevent pregnancy and agreement to continue to practice an acceptable method of contraception for the duration of their participation in the study and up to 3 months after the last dose of efalizumab
• Have given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care
• Discontinuation of any systemic psoriasis treatment prior to commencement of the study drug. No washout period is required for these agents prior to starting study and receiving first dose of study drug (efalizumab)
• Discontinuation of all biologic agents (other than efalizumab) 3 months prior to receiving first dose of study drug (efalizumab)
• Discontinuation of any investigational drug or treatment 3 months prior to Study Day 0 or as per washout requirements from previous protocol
• No primary vaccinations (e.g., tetanus, booster, influenza vaccine) at least 14 days prior to first dose of study drug
• The participant must be willing and able to comply with the protocol requirements for the duration of the study

Exclusion Criteria:

• Guttate, erythrodermic, or pustular psoriasis as sole or predominant form of psoriasis
• Participants who have previously been on efalizumab treatment who withdrew due to lack of efficacy or an adverse event. If withdrawal was due to another non-drug reason (vaccination, or infection) then the patient can be included in this study
• History of severe allergic or anaphylactic reactions to humanised monoclonal antibodies
• History of or ongoing uncontrolled bacterial, viral, fungal, or atypical mycobacterial infection
• History of opportunistic infections (eg, systemic fungal infections, parasites)
• Seropositivity for human immunodeficiency virus (HIV). Participants will undergo mandatory testing at screening. Participants who are positive for HIV will be excluded
• Pregnancy or breast feeding
• White Blood Cell (WBC) count less than (<) 4*10^9 per liter or greater than (>) 14*10^9 per liter
• Participants with a history of clinically significant thrombocytopenia, bleeding disorders or a platelet count <100*10^9 per liter
• Seropositivity for hepatitis B or C virus. Participants will undergo testing at screening. Participants who are positive for hepatitis B antigen or hepatitis C antibody will be excluded
• History of active tuberculosis (TB) or currently undergoing treatment for TB within one year prior to Study Day 0. Chest X-ray (within 3 months prior to Study Day 0) is required for high-risk participants. Participants with a positive chest X-ray will be excluded
• Presence of malignancy within the past 5 years, including lymphoproliferative disorders. Participants with a history of fully resolved basal cell or squamous cell skin cancer may be enrolled
• Hospital admission for cardiac disease, stroke, or pulmonary disease within the last year
• Any medical condition that, in the judgment of the investigator, would jeopardize the participant's safety following exposure to study drug