A Study of the Safety and Efficacy of Ustekinumab in Patients With Psoriatic Arthritis With and Without Prior Exposure to Anti-TNF Agents

This study is a randomized (patients are assigned different treatments based on chance),
double-blind (neither the patient nor the physician knows whether drug or placebo is being
taken, or at what dosage), parallel-group, multicenter study to evaluate the effectiveness
and safety of ustekinumab compared to placebo in the treatment of patients with active
psoriatic arthritis who have or are currently receiving treatment with a disease-modifying
antirheumatic drug (DMARD) and/or a nonsteroidal anti-inflammatory drug (NSAID), including
those who have previously received anti-tumor necrosis factor (anti-TNF) agents [(examples
are infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira)]. The primary
effectiveness endpoint will be measured by the reduction in signs and symptoms of arthritis,
as defined by 20% improvement from baseline in American College of Rheumatology (ACR)
measurements of arthritis at Week 24. The study will additionally look at higher levels of
joint improvement (ie, 50% or 70% improvement from baseline) and improvement in activity and
quality of life, as well as the impact of ustekinumab on psoriatic skin lesions. Safety
assessments will be performed throughout the study and include obtaining and evaluating
laboratory tests, vital signs (eg, blood pressure) and the occurrence and severity of
adverse events (side effects). Patients will be assigned to one of three treatment groups.
Patients will receive either 45 mg ustekinumab, 90 mg ustekinumab, or placebo at Weeks 0, 4
and every 12 weeks until Week 40. Patients who do not have >=5% improvement in their disease
(tender and swollen joints) at Week 16 may be eligible to receive an increase or change to
their ustekinumab dosage. Ustekinumab 45 mg, 90 mg, or placebo subcutaneous injections at
Weeks 0 and 4 followed by every-12-week dosing with the last dose at Week 40. Early escape
possibility at Week 16. Patients randomized to placebo will crossover to receive ustekinumab
at Weeks 24 and 28 followed by every-12-week dosing with the last dose at Week 40. Expected
duration of exposure to study agent including follow up for safety is 60 weeks.

Inclusion Criteria:

- Have had a documented diagnosis of psoriatic arthritis (PsA) at least 6 months

- Have a diagnosis of active PsA at the time of entry into the study with at least 5
tender and 5 swollen joints at baseline

- May have previously received at least 8 weeks of etanercept, adalimumab, golimumab or
certolizumab pegol or at least 14 weeks of infliximab or proven inability to tolerate
anti-TNF therapy for 8-14 weeks

- If the patient is using methotrexate, they should have started treatment at a dose
not to exceed 25 mg/week at least 3 months prior to the beginning of the study and
should have no serious toxic side effects attributable to methotrexate

Exclusion Criteria:

- Have other inflammatory diseases, including but not limited to rheumatoid arthritis,
ankylosing spondylitis, systemic lupus erythematosus, or Lyme disease

- Have used any therapeutic agent targeted at reducing IL-12 or IL-23, including but
not limited to ustekinumab and ABT-874

- Have used infliximab, golimumab or certolizumab pegol within 12 weeks of first study
drug injection, or etanercept or adalimumab within 8 weeks of first study drug
injection

- Have a medical history of latent or active granulomatous infection, including TB,
histoplasmosis, or coccidioidomycosis, prior to screening

- Have any known malignancy or have a history of malignancy (with the exception of
basal cell carcinoma, squamous cell carcinoma in situ of the skin, or cervical
carcinoma in situ that has been treated with no evidence of recurrence, or squamous
cell carcinoma of the skin that has been treated with no evidence of recurrence
within 5 years of the beginning of the study