Ustekinumab, a human antibody used to treat arthritis, significantly induces response and remission in patients with moderate to severe Crohn’s disease, found a University of California San Diego School of Medicine study.
“A high percentage of the patients in the study who had not responded to conventional therapies were in clinical remission after only a single dose of intravenous ustekinumab,” said Dr William J Sandborn, professor of medicine at UC San Diego School of Medicine and director of the Inflammatory Bowel Disease Centre at UC San Diego Health. “Finding effective new treatment options for this patient population is critical because Crohn’s disease can dramatically impact a person’s quality of life. Patients suffering from this disease may go to the bathroom up to 20 times a day and experience abdominal pain, ulcers and a reduced appetite.”
Crohn’s disease is a chronic inflammatory disease of the gastrointestinal tract that affects approximately 700,000 people in the US. It can affect any part of the GI tract but it is more commonly found at the end of the small intestine (the ileum) where it joins the beginning of the large intestine (or colon). Crohn’s disease is usually treated with glucocorticoids, immune-suppressants, tumour necrosis factor (TNF) antagonists or integrin inhibitors.
“The drawbacks of these therapies include an increased risk of infection and cancer, and limited efficacy,” said Sandborn. “Ustekinumab has not been associated with an increased risk of serious adverse events.”
The rates of remission response in the randomised study at week six among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving a placebo. The study also found subcutaneous (injected) ustekinumab every 8 to 12 weeks maintained remission in patients.
“This study indicates that ustekinumab may have a long duration of action, a likelihood that may become better understood in future trials,” said Sandborn. “Our current findings offer hope for those suffering from this debilitating gastrointestinal tract disease.”
Background: Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy.
Methods: We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these 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 clinical response at week 6 (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).
Results: The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P Conclusions: Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy.
Brian G Feagan, William J Sandborn, Christopher Gasink, Douglas Jacobstein, Yinghua Lang, Joshua R Friedman, Marion A Blank, Jewel Johanns, Long-Long Gao, Ye Miao, Omoniyi J. Adedokun, Bruce E Sands, Stephen B Hanauer, Severine Vermeire, Stephan Targan, Subrata Ghosh, Willem J. de Villiers, Jean-Frédéric Colombel, Zsolt Tulassay, Ursula Seidler, Bruce A Salzberg, Pierre Desreumaux, Scott D Lee, Edward V Loftus, Jr, Levinus A Dieleman, Seymour Katz, Paul Rutgeerts