Therapy of Inflammatory Bowel Disease: What to Expect in the Next Decade

David A. Leiman; Gary R. Lichtenstein


Curr Opin Gastroenterol 

In This Article

Antiinterleukin 12/23

Interleukin-12 (IL-12) and IL-23 are proinflammatory cytokines involved in the pathophysiology of Crohn's disease.[23] These molecules help to regulate type-1 helper T-cell responses and assist in the recruitment of macrophages. After initial lackluster results, ustekinumab, a fully human IgG1 monoclonal antibody to IL-12 and IL-23, demonstrated benefit when given subcutaneously to patients with moderate-to-severe active disease.

The CERTIFI study, a phase IIb study, randomized 526 patients who were previously resistant to anti-TNF-α therapy to receive either placebo or intravenous ustekinumab at doses of 1, 3, or 6 mg/kg. Clinical response based on CDAI scores was assessed at week 6. Only 23.5% of patients receiving placebo had response versus 36.6, 34.1, and 39.7%, respectively, for 1, 3, and 6 mg/kg of ustekinumab. These findings were only statistically significant for the 6 mg/kg group (P = 0.005). In the maintenance phase of the study, patients who had a response to induction therapy and those who did not were rerandomized to either receive subcutaneous ustekinumab or placebo.[24] Response was assessed at week 22 and there was a statistically significant difference in clinical remission rates (41.7 versus 27.4%; P = 0.03) and clinical response (69.4 versus 42.5%; P < 0.001). These findings are encouraging and potentially significant, presenting a nonsurgical approach to patients who previously had few medical options. In 2012, the FDA approved the drug for use in psoriatic arthritis, and phase III studies in Crohn's disease are being conducted.[25]