Originally published by our sister publication Gastroenterology & Endoscopy News
Chair of the Digestive Disease & Surgery Institute
Cleveland Clinic, Cleveland
This month’s report focuses on the anti-interleukin treatments for inflammatory bowel disease, specifically those that target interleukin 12 and/or interleukin 23.
The first study compares clinical and endoscopic remission rates when using risankizumab (Skyrizi, AbbVie) or ustekinumab (Stelara, Janssen) for treating people with moderate to severe Crohn’s disease. The study is not a prospective, controlled study, but we still need this kind of data. The research shows an indirect comparison between trials that tested either risankizumab or ustekinumab, seeking to tease out which therapy has better clinical and endoscopic remission rates.
Despite the limitation of the study, its findings accord with what I see in my clinical practice—namely, that risankizumab leads to robust remission rates. Mechanistically, the explanation for this may be that risankizumab is a more potent inhibitor of IL-23 than ustekinumab; IL-23 activity seems to be an important contributor to Crohn’s disease. In addition, the dose for risankizumab appears to be higher.
All that said, it should be acknowledged that scientific data are lacking for potential differences between ustekinumab and risankizumab. This study doesn’t mean that we should stop using ustekinumab. It’s still a good therapy, and, in some cases, a patient’s insurance may only cover ustekinumab. This study suggests that, when we have a choice between the two therapies, the selectivity of IL-23 may favor risankizumab.
The other study focuses on the effects of different treatment strategies for ustekinumab. The researchers examined whether standard of care or more intensified treatment better improved patient quality of life and ability to work. They found no statistically significant difference between the two approaches on these outcomes, which means that for most patients, a standard of care, rather than a more frequent course of ustekinumab, is fine.
This study result was somewhat surprising; many gastroenterologists, myself included, expected the intensified treatment approach to outperform standard of care. But this goes to show why we do research to rigorously test our assumptions. That’s why this work is important.
Of note, the study we are reviewing examined quality of life and work productivity and not clinical or endoscopic end points. In my practice, I have found that there are some patients with IBD who really do need intensified dosing of their biologic therapy. In these cases, the standard course does not yield enough clinical benefit. The challenge is that often payors will not cover treatment that deviates from the labeled dosing and interval of administration.
Risankizumab Versus Ustekinumab for Crohn’s Disease
Adv Ther 2023 Jun 27. doi:10.1007/s12325-023-02546-6
This study compares the results of three phase 3 trials of risankizumab with three phase 3 trials of ustekinumab for treating moderate to severe Crohn’s disease.
The authors assessed which of the two treatments led to a greater reduction in the Crohn’s Disease Activity Index (CDAI), measured by a decrease of at least 100 points or a total score less than 150. They also measured how many patients reached remission (a CDAI score of 150 or less); endoscopic improvement (at least a 50% reduction in the Simple Endoscopic Score for Crohn’s Disease from baseline); and endoscopic remission (a Simple Endoscopic Score of 2 or less).
Risankizumab outperformed ustekinumab on all of these measures, during induction treatment. The difference in CDAI remission rate was a statistically significant 15% greater (95% CI, 5%-25%) for risankizumab. Differences in endoscopic response (26%; 95% CI, 13%-40%) and endoscopic remission (9%; 95% CI, 0%-19%) also were significant. During the maintenance treatment phase, CDAI remission rates were similar with risankizumab and ustekinumab.
The STARDUST Trial
United European Gastroenterol J 2023;11(5):410-422
This study compared a standard-of-care ustekinumab administration schedule with a treat-to-target approach that sometimes resulted in dosing as often as every four weeks in patients with active moderate to severe Crohn’s disease. Patients were followed for two years.
The researchers assessed which treatment strategy yielded better quality of life using various measures such as the Inflammatory Bowel Disease Questionnaire and the Hospital Anxiety and Depression Scale. They also compared time lost from work for the two approaches and calculated Work Productivity and Activity Impairment scores for both approaches.
There was no statistically significant difference in health-related quality of life or work readiness, regardless of treatment strategy.