Robert Stott , 2025-05-16 11:00:00
Key takeaways:
- B-cell depletion with inebilizumab reduced flare risk for pancreatic and/or biliary IgG4-related disease.
- It also reduced overall glucocorticoid use for disease control in both groups.
SAN DIEGO — Inebilizumab was especially effective for patients with pancreatic and biliary immunoglobulin G4-related disease, with significantly reduced glucocorticoid use for disease control, according to analysis of the MITIGATE trial.
Although data from The New England Journal of Medicine published in November 2024 confirmed that inebilizumab (Uplizna, Amgen) significantly reduced the risk for IgG4-related disease (IgG4-RD) flares and improved the likelihood of attaining glucocorticoid-free complete remission, its benefit for frequently reported pancreatic and hepatobiliary manifestations of the disease had not been established.
“More than 50% of patients with IgG4-related disease have these kind of pancreatobiliary manifestations,” lead investigator Matthias Löhr, MD, PhD, professor of gastroenterology and hepatology and senior physician at Karolinska Institute in Stockholm, told Healio. “What we have shown in this study is that after initial treatment with first-line glucocorticoids, inebilizumab will be second-line — a new standard that will change clinical practice.”
In a subgroup analysis of the phase 3 MITIGATE trial presented at Digestive Disease Week, Löhr and colleagues examined safety and efficacy outcomes among patients with IgG4-RD who exhibited baseline disease activity in the pancreas, bile ducts or both organs. Eligible patients included those with a history of IgG4 disease involvement in at least two organs and who had experienced a disease-related flare necessitating glucocorticoid treatment during initial screening.
At baseline, the researchers reported that 38% of patients exhibited disease activity in the pancreas and 21% in the bile ducts, with 19% showing activity in both organs.
Patients were randomly assigned 1:1 to receive either inebilizumab (n = 68) or placebo (n = 67) on day 1, day 15 and week 26 during the 52-week treatment period. Additionally, steroids were tapered and ultimately discontinued by week 8, with immunosuppressive therapies for IgG4-RD restricted for the remainder of the study.
According to study results, patients with IgG4-RD affecting the pancreas (66.7%) and bile ducts (84.6%) were more likely to achieve glucocorticoid-free, flare-free complete remission with inebilizumab compared with the overall IgG4-RD population (58.8%).
In addition, patients with pancreatobiliary involvement of IgG4-RD who received inebilizumab demonstrated significantly reduced need for glucocorticoids to control the condition.
“The surprising finding in this sub-analysis was that the effect of the drug was even better in patients with these manifestations compared with the entire group,” Löhr said. “With regard to reduced annualized flare rate vs. placebo during the observation period, the effect was even bigger in the pancreatobiliary group compared with the overall [IgG4-RD] group. I must admit, that was something I didn’t count on.”
The incidence of adverse events for patients with gastrointestinal involvement of IgG4-RD was similar to that previously reported for the overall IgG4-RD population. The most common adverse events were observed among patients with both pancreatic and biliary involvement and included back pain, COVID-19, hyperuricemia, lymphopenia, fever and urinary tract infection.
“For the first time, we have a drug that is not only approved for IgG4-related disease, but works best in the GI manifestations of the disease, including autoimmune pancreatitis and immune-related cholangitis,” Löhr told Healio. “This will be a game changer in clinical practice, especially for patients who have a flare or rare manifestation of the disease and do not respond to initial therapy with steroids.”
For more information:
Matthias Löhr, MD, PhD, can be reached at gastroenterology@healio.com.
Sources/Disclosures
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Lohr M. Safety and efficacy of inebilizumab in IgG4-related disease in participants with pancreatic and biliary involvement: Results from the phase 3 MITIGATE trial. Presented at: Digestive Disease Week; May 3-6; San Diego.
Disclosures:
Amgen funded the MITIGATE trial. Lohr reports committee membership during the trial. Please see the study for all other authors’ relevant financial disclosures.
