Using new drugs, targeting new pathways
The recently published CALM study tested the hypothesis that treating to a target of no biochemical inflammation (elevated C reactive protein or fecal calprotectin) would be better than symptom-driven treatment alone. Treatment escalation for active disease included adalimumab every other week, then weekly adalimumab, and finally the addition of azathioprine. At the end of the study, patients whose medical therapy was based on both symptoms and biochemical inflammation had a higher degree of mucosal healing than did patients in the clinical management group (Lancet. 2018 Dec 23;390[10114]:2779-89).
Ustekinumab is a monoclonal antibody that targets the p40 subunit of interleukin-12 and interleukin-23 and is approved for Crohn’s disease. Various pharmaceutical companies are now developing anti-p19 antibodies, which block IL-23 only; at DDW 2018, the anti–IL-23 mirikizumab was shown to be effective in UC. We are also seeing the availability of oral medications for IBD. Just prior to DDW, tofacitinib ( N Engl J Med. 2017 May 4;376:1723-36 ), a Janus kinase (JAK) 1/3 inhibitor, which has an effect on multiple different cytokine pathways, received approval for UC. Other JAK inhibitors with different specificities are being tested in trials of UC and Crohn’s disease.
Dr. Abreu is a professor of medicine, a professor of microbiology and immunology, and the director of the Crohn’s & Colitis Center at the University of Miami Miller School of Medicine. She has no conflicts of interest. Dr. Abreu made her comments during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.
