Anti-Interleukins Show Value in the Treatment of IBD

Anti-interleukin (IL)-12 and anti-IL-23 agents present valuable treatment options for patients with inflammatory bowel disease (IBD), according to a presentation on Thursday by William J Sandborn, MD, FACG, at the 2018 AIBD Meeting.

Several biologic drugs targeting IL-12 and IL-23, two important cytokines in the immunological pathway of IBD, have recently become available or are in various stages of drug development. These agents include the IL-12/23 inhibitor ustekinumab and the IL-23 inhibitors brazikumab, risankizumab, and mirikizumab.

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Ustekinumab has been approved for the treatment of moderately to severely active Crohn disease in patients who have failed or were intolerant to treatment with immunomodulators or corticosteroids, or who have failed or were intolerant to treatment with one or more tumor necrosis factor (TNF) inhibitors. The drug is also used for the treatment of psoriasis and psoriatic arthritis.

In his presentation, Dr Sandborn reviewed the clinical studies supporting the efficacy and safety of ustekinumab. Ustekinumab demonstrated good clinical response at week 6 and clinical remission at week 8. He stressed that the drug is fast-acting, causing a rapid reduction in Crohn’s Disease Activity Index (CDAI) scores and C-reactive protein (CRP) levels as early as week 3 of the study.

Though these studies have shown consistent effectiveness, he said, the optimal dose of ustekinumab has been less clear. Additionally, he emphasizes that the effectiveness of ustekinumab in the maintenance setting is greater in the anti-TNF naïve patient population than the anti-TNF refractory patient population.

In the maintenance trial, all responding patients from UNITI‐1 (TNF‐antagonist failures) and UNITI‐2 (conventional therapy failures) were pooled together and given treatment every 8 weeks or every 12 weeks. While both regimens were shown to be effective, better results were seen with 8-week dosing. The study, as well as systematic reviews that have been performed, have seemed to confirm that ustekinumab works better in patients who failed on conventional therapies vs those who failed on TNF antagonists. Dr Sandborn noted, however, that the latter group includes both patients who initially responded and then failed as well as nonresponders. Dr Sandborn also stressed ustekinumab has a surprisingly good safety profile for a systemic drug, which was largely similar to that of placebo in clinical trials.

Dr Sandborn concluded his presentation by highlighting the anti-IL-23 therapies brazikumab, risankizumab, and mirikizumab, which are currently being evaluated for use in patients with Crohn disease and ulcerative colitis. These novel treatment options will continue to present an alternative for patients with IBD who do not respond to conventional therapies or TNF inhibitors.

—Kara Rosania

Reference:

Sandborn W. Positioning Anti-IL-12 and Anti-IL-23 inhibitors. Presented at: Advances in Inflammatory Bowel Diseases; December 13-15, 2018; Orlando, FL. https://www.consultant360.com/meetings/aibd.