Chair of the Digestive Disease & Surgery Institute
Cleveland Clinic, Cleveland
This month I am discussing two studies from 2022 that many readers may already be aware of, but which are still worth highlighting due to their practice-changing implications. Both studies appeared in the Lancet and were discussed at the 2022 annual Advances in Inflammatory Bowel Diseases meeting, the largest conference of its kind in North America, which I co-chair.
The first study is a report on two international phase 3 trials, ADVANCE and MOTIVATE, which show the benefit of the monoclonal antibody risankizumab (Skyrizi, AbbVie) for treating moderately to severely active Crohn’s disease. Patients in MOTIVATE had not responded to biologics and those in ADVANCE had not responded to biologics or conventional therapy. Compared with placebo, risankizumab given as induction therapy three separate times (weeks 0, 4 and 8) yielded significant clinical remission and endoscopic response rates by week 12. This was true whether or not participants had received biologic therapy previously. Considering that healing the bowel can take a year or longer in people with Crohn’s, these results are excellent. After this paper’s publication in May 2022, the FDA approved risankizumab to treat Crohn’s.
The other study focuses on use of the Janus kinase inhibitor upadacitinib (Rinvoq, AbbVie)—approved as a treatment for UC in March 2022—as induction (U-ACHIEVE and U-ACCOMPLISH) and maintenance (U-ACHIEVE maintenance) therapy for moderately to severely active ulcerative colitis, in patients for whom anti–tumor necrosis factor therapies had not been effective. Compared with placebo, upadacitinib achieved significantly greater clinical remission.
On a personal note, these studies reaffirm my experience treating patients with IBD in clinical practice. These studies are landmarks in our field.
Risankizumab as Induction Therapy for CD
(Lancet 2022;399[10340]:2015-2030)
In ADVANCE, investigators enrolled 931 patients to receive risankizumab 600 mg (n=373) or 1,200 mg (n=372) or placebo (n=186) (ClinicalTrials.gov Identifier: NCT03105128). A total of 850 patients were included in the final analysis. The patients received infusions at weeks 0, 4 and 8.
By week 12, 45% of the group receiving the 600-mg dose, 42% of those receiving 1,200 mg and 25% of the placebo group had achieved clinical remission on the Clinical Disease Activity Index (CDAI) (P<0.0001). In addition, the endoscopic response rate at week 12 was 40% with 600 mg, 32% with 1,200 mg and 12% with placebo (P<0.0001).
In MOTIVATE, investigators randomly assigned 618 patients to receive 600 (n=206) or 1,200 mg (n=205) of risankizumab, or placebo (n=207); 569 patients were analyzed (ClinicalTrials.gov Identifier: NCT03104413).
The CDAI remission rate at 12 weeks was higher with both risankizumab doses than placebo (42% with 600 mg and 40% with 1,200 mg vs. 20% with placebo; P<0.0001). The endoscopic response rate was also higher for the intervention arms than the placebo arm (29% with 600 mg, 34% with 1,200 mg and 11% with placebo; P<0.0001).
There were no significant differences in the effects of the two doses and no new safety signals.
Upadacitinib as Induction/Maintenance Therapy for UC
(Lancet 2022;399[10341]:2113-2128)
In the U-ACHIEVE trial, investigators enrolled 474 participants, who received 45 mg of upadacitinib daily (n=319) or placebo (n=155) for eight weeks (ClinicalTrials.gov Identifier: NCT02819635). At the eight-week time point, 26% of patients who received upadacitinib had achieved clinical remission by the Adapted Mayo Score, compared with 5% of the placebo group (P<0.0001).
The U-ACCOMPLISH trial included 522 patients who received 45 mg of upadacitinib daily (n=345) or placebo (n=177) (ClinicalTrials.gov Identifier: NCT03653026). At eight weeks, 34% of upadacitinib-treated patients and 4% of the placebo group had achieved clinical remission (P<0.0001).
In a follow-up maintenance trial that lasted one year, both 15 and 30 mg of upadacitinib were better at bringing about clinical remission than placebo. No new safety signals were identified.
—Compiled and written by Marcus A. Banks
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