Ustekinumab Effective and Safe in Crohn's Colitis Save

The New England Journal of Medicine has reported the results of a large clinical trial demonstrating the efficacy of ustekinumab (Stelara) in treating patients with active Crohn's disease (CD). (Citation source http://buff.ly/2gsSNcs)

Ustekinumab is a monoclonal antibody that binds the p40 subunit of interleukin-12 (IL-12) and IL-23 that is approved for use in psoriasis and psoriatic arthritis. In September 2016 the FDA and EMA approved ustekinumab for use in moderate to severe Crohn's disease based on these two now published trials.

The UNITI-1 trial included 741 CD patients who randomized to either subcutaneous ustekinumab (either 130 mg or  6 mg/kg) or placebo in two inductions. The UNITI-1 trial included patients with a primary or secondary nonresponse to tumor necrosis factor inhibitors (TNFi).

The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these two induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a week 6 response defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150).

The week 6 responses were significantly higher for ustekinumab compared to placebo for the UNITI-1 trial (33% vs. 21%) and the UNITI-2 trial (>51% vs. 28%).

Ustekinumab did equally well with 53% (q 8 wks), 49% (q 12 wks.) compared with 36% placebo response at week 44 (P=0.005 and P=0.04, respectively). No new or unexpected adverse events were observed.

Dr. Lianne Gensler presented a combined safety analysis of ustekinumab in Pso, PsA and CD at the recent 2016 ACR Annual meeting.  A combined 2867 patients received UST for > 12 months. Compared to placebo, discontinuation rates were similar, adverse events and serious adverse events were significantly lower compared to PBO. 

Serious infections were lower and major CV (MACE) events and malignancies were similar to PBO. No deaths in PsA or CD were reported.

Ustekinumab has also been under investigation for use in ankylosing spondylitis, giant cell arteritis and rheumatoid arthritis.