OBJECTIVE: Interleukin (IL)-12 and IL-23 have been implicated in the 
pathogenesis of rheumatoid arthritis (RA). The safety and efficacy of 
ustekinumab, a human monoclonal anti-IL-12/23 p40 antibody, and guselkumab, a 
human monoclonal anti-IL-23 antibody, were evaluated in adults with active RA 
despite methotrexate (MTX) therapy.
METHODS: Patients were randomly assigned (1:1:1:1:1) to receive placebo at weeks 
0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 8 weeks 
(n=55), ustekinumab 90 mg at weeks 0, 4 and every 12 weeks (n=55), guselkumab 
50 mg at weeks 0, 4 and every 8 weeks (n=55), or guselkumab 200 mg at weeks 0, 4 
and every 8 weeks (n=54) through week 28; all patients continued a stable dose 
of MTX (10-25 mg/week). The primary end point was the proportion of patients 
with at least a 20% improvement in the American College of Rheumatology criteria 
(ACR 20) at week 28. Safety was monitored through week 48.
RESULTS: At week 28, there were no statistically significant differences in the 
proportions of patients achieving an ACR 20 response between the combined 
ustekinumab group (53.6%) or the combined guselkumab group (41.3%) compared with 
placebo (40.0%) (p=0.101 and p=0.877, respectively). Through week 48, the 
proportions of patients with at least one adverse event (AE) were comparable 
among the treatment groups. Infections were the most common type of AE.
CONCLUSIONS: Treatment with ustekinumab or guselkumab did not significantly 
reduce the signs and symptoms of RA. No new safety findings were observed with 
either treatment.
TRIAL REGISTRATION NUMBER: NCT01645280.