Based on these and other recent findings, the drug could be used as a first-line treatment and even displace ustekinumab (Stelara, Janssen), which itself was approved by the US Food and Drug Administration (FDA) only for Crohn’s disease in 2016, according to David Rubin, MD, the Joseph B. Kirsner Professor of Medicine at the University of Chicago in Illinois.
“The drug works fast,” Rubin told Medscape Medical News. “If you start this therapy in patients with moderate to severe Crohn’s disease, they’re likely to feel better within the first few weeks.”
Rubin presented the findings on the drug’s early onset here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting. A related trial presented here showed the drug continuing to perform well up to 52 weeks.
Advances in immunomodulation have allowed drug companies to feed multiple new therapies into the pipeline for Crohn’s disease and related conditions in recent years, giving hope to the many patients who have not been able to benefit from older classes of drugs, such as biologics.
A humanized immunoglobin G1 (IgG1) monoclonal antibody, risankizumab blocks interleukin (IL) 23 by binding to its p19 subunit. IL-23 is a cytokine implicated in several chronic immune disorders, including Crohn’s disease and psoriasis. Researchers hope that risankizumab will prove more selective, with a better safety profile, than previous drugs in its class. The FDA approved risankizumab in April 2019 for the treatment of moderate-to-severe plaque psoriasis.
MOTIVATE and ADVANCE Studies
The two induction trials for Crohn’s disease enrolled slightly different populations.
The MOTIVATE study enrolled patients who had responded inadequately or were intolerant to biologic therapy. In this trial, the investigators assigned 205 patients to 1200 mg of risankizumab, 206 patients to 600 mg of risanbizumab, and 207 patients to placebo.
The ADVANCE study enrolled patients who had responded inadequately or could not tolerate either biologic or conventional therapy. In this trial, investigators randomly assigned 372 patients to 1200 mg of risankizumab, 373 patients to 600 mg of risankizumab, and 186 patients to placebo.
In both trials, intravenous injections were given at weeks 0, 4, and 8.
The researchers defined a Crohn’s Disease Activity Index (CDAI) clinical remission as a score less than 150. They defined a Stool Frequency and Abdominal Pain Score (SF/APS) clinical remission as a soft stool frequency of no more than 2.8, and an abdominal pain score of no more than 1 and not worse than baseline.
A CDAI clinical response was at least a 100-point decrease from baseline. The SF/APS enhanced clinical response was at least a 60% decrease in average daily stool frequency or at least a 35% decrease in average daily abdominal pain, with both not worse than baseline.
At 4 weeks, they found that the percentage of patients who achieved CDAI clinical remission in both risankizumab groups of both studies was greater than in the placebo group.The difference was statistically significant (P ≤ .01 in ADVANCE and P ≤ .05 in MOTIVATE), and it continued to grow at 8 weeks and 12 weeks.
By 12 weeks in the ADVANCE trial, according to a press release, 45% of patients on the 600-mg dose of risankizumab and 42% on the 1200-mg dose of risankizumab had achieved CDAI clinical remission, compared with 25% of those on placebo, which was statistically significant (P < .001). For the MOTIVATE trial, the results were also significantly better for patients in the risankizumab groups than those in the placebo group.
In both trials, the treated groups continued to improve faster than the placebo groups through 12 weeks. Improvements in SF/APS enhanced clinical response largely paralleled those for CDAI clinical remission.
“It did show very good results,” said session moderator Jonathan Leighton, MD, a professor of medicine and chair of the Division of Gastroenterology at Mayo Clinic in Phoenix, Arizona, in an interview with Medscape Medical News. “But basically, it’s so early that we don’t have all the data.” In particular, he would have liked to see whether patients responded to the drug before week 4.
In FORTIFY, the maintenance trial that followed, the researchers rerandomized those patients who had responded to risankizumab into three groups. Two groups received subcutaneous injections of risankizumab, with 179 patients getting 360 mg and another 179 patients getting 180 mg. The placebo group included the remaining 184 patients.
At week 52, 40.9% of patients in the placebo group were in clinical remission, compared with 52.2% in the 360-mg group and 55.4% in the 180-mg group, which was statistically significant (P = .005 for 360 mg, and P = .003 for 180 mg.)
“It showed us that [risankizumab] could achieve deep remission, which means patients achieving remission endoscopically in combination with clinical remission,” said the presenter, Marla Dubinsky, MD, a professor of pediatrics and medicine in the division of pediatric gastroenterology at Icahn School of Medicine at Mount Sinai in New York City, in an interview with Medscape Medical News.
Over the 52 weeks, deep remission and endoscopic remission rates increased in the 360-mg group, held steady in the 180-mg group, and decreased in the placebo group. Mean fecal calprotectin and C-reactive protein levels decreased in the risankizumab groups and increased in the placebo group.
There were more total treatment-emergent adverse events per 100 patient-years in the placebo group (339.7) than in the 360-mg group (269.3) or the 180-mg group (283.5). The same difference between groups was also true of severe treatment-emergent adverse events. Serious events and events leading to discontinuation were similar in the three groups.
American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting: Abstract 22 presented October 26, 2021, and Abstract 63 presented October 27, 2021.
Leighton reports financial relationships to Olympus and Pfizer. Rubin reports financial relationships to AbbVie, AltruBio, Allergan, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos, Connect Biopharma, GalenPharma/Atlantica, Genentech/Roche, Gilead, InDex Pharmaceuticals, Ironwood, Iterative Scopes, Janssen, Lilly, Materia Prima Farmaceutica, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TECHLAB. Dubinsky reports financial relationships to all or most of the companies making drugs for inflammatory bowel disease. The studies were funded by AbbVie.
Laird Harrison writes about science, health and culture. His work has appeared in national magazines, in newspapers, on public radio, and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at www. lairdharrison.com or follow him on Twitter: @LairdH.