Anti-IL-23 therapy effective in treating IBD
MAUI, Hawaii — Interleukin-23 inhibitors are effective for induction and maintenance of remission in Crohn’s disease and ulcerative colitis, according to an expert at the GUILD Conference 2020.
“So we have all these great new mechanisms and, this year at GUILD, we wanted to take some time to delve into some of them,” Uma Mahadevan, MD, professor of medicine at UCSF Center for Colitis and Crohn’s Disease, said during a presentation.
Mahadevan cited a study that found that 66% of patients with CD who were in remission at week 0 were still in remission at week 44 after receiving Stelara (ustekinumab, Janssen) every 8 weeks.
A study published in The New England Journal of Medicine found that 47% of patients with CD taking ustekinumab every 8 weeks and not on corticosteroids were still in remission.
Ustekinumab was able to recapture a response in 69% of patients with CD experiencing a partial or secondary loss of response in a study by Heron and colleagues.
“If you had a patient who was doing well on ustekinumab and they lost response, you can re-induce with a single IV dose and continue on every 8-week dosing and recapture that response,” Mahadevan said.
Mahadevan reports that, in moderate to severe UC, ustekinumab achieved clinical remission, endoscopic and histologic improvement, maintained clinical response and was effective in previous biologic failures.
Mahadevan reported that ustekinumab has an excellent safety profile. Results from the PSOLAR study found that ustekinumab had no increased risk for malignancy, major adverse cardiovascular events, serious infection or mortality.
A study by Loftus and colleagues found that ustekinumab had a lower rate of serious infections and tuberculosis than anti-tumor necrosis factors.
“If a patient has inflammatory bowel disease, do not give them an IL-17 inhibitor,” Mahadevan said. Two studies found that Siliq (brodalumab, Bausch Health) and secukinumab (Cosentyx, Novartis) worsen CD.
A study published in The Lancet found that Skyrizi (risankizumab-rzaa, AbbVie) was effective in treating patients, even those who received anti-TNF for CD.
Another anti-IL-23, brazikumab (AbbVie/Allergan), has been shown to be safe and effective for CD, according to a study published in Gastroenterology.
A phase 2 study by Sands and colleagues found that another IL-23 inhibitor, mirikizumab, is safe and effective for inducing remission in moderate to severe CD.
The only IL-23 inhibitor commercially available in the rheumatology space is Tremfya (guselkumab, Janssen), Mahadevan said.
“If all goes well, we’ll have several IL-23 inhibitors to work with for both Crohn’s disease and ulcerative colitis in the upcoming years,” Mahadevan said.
Phase 3 trials of risankizumab and mirikizumab in treating Crohn’s disease and Ulcerative Colitis are currently ongoing. – by Kaitlin McGee
Mahadevan U. Targeting the IL-23 Pathway. Presented at: Guild Conference 2020; Feb. 16-19, 2020; Maui, Hawaii.
Disclosure: Mahadevan reports consulting for AbbVie, Janssen, Pfizer and Takeda and receiving a research grant from Pfizer