BACKGROUND: Repeated subcutaneous injections of a monoclonal antibody against 
the p40 subunit of interleukins 12 and 23, ustekinumab, were used to treat 
patients with relapsing-remitting multiple sclerosis (RRMS) to assess the drug's 
safety, efficacy, and pharmacokinetics.
METHODS: In this phase II, multicentre, randomised, double-blind, 
placebo-controlled study, 249 patients with RRMS, aged 18-65 years, were 
eligible to be assigned equally (by a central randomisation procedure based on 
study site and presence or absence of gadolinium-enhancing T1-weighted lesions 
at baseline) to one of five groups that received placebo or four different 
ustekinumab dosages at weeks 0, 1, 2, 3, 7, 11, 15, and 19. Ustekinumab doses 
were 27 mg, 90 mg q8w, 90 mg, or 180 mg; the 90 mg q8w dosage group received 
placebo substitute at weeks 7 and 15. The primary endpoint was the cumulative 
number of new gadolinium-enhancing T1-weighted lesions on serial cranial MRI 
through week 23. Patients were followed up through week 37. Analysis was by 
intention to treat. This trial is registered with ClinicalTrials.gov, number 
NCT00207727.
FINDINGS: From August, 2004, to December, 2006, 249 patients underwent 
randomisation (49 for placebo; 50 for each ustekinumab group). Ustekinumab 
treatment did not show a significant reduction in the primary endpoint for any 
dosage groups versus placebo. At week 37, adverse events occurred in 38 (78%) 
placebo-treated patients and 170 (85%) ustekinumab-treated patients, with 
infections most commonly reported. Serious adverse events occurred in one (2%) 
placebo-treated patient and six (3%) ustekinumab-treated patients. Malignant 
diseases were reported in two patients shortly after the initiation of 
ustekinumab treatment; both patients were withdrawn from the trial and given 
appropriate treatment, which resulted in complete remission. No serious 
infections, cardiovascular events, or exacerbation of demyelinating events 
occurred. A dose-dependent increase in serum concentrations of ustekinumab was 
recorded.
INTERPRETATION: Ustekinumab is generally well tolerated but does not show 
efficacy in reducing the cumulative number of gadolinium-enhancing T1-weighted 
lesions in multiple sclerosis.