‘Beyond doubt’: B-cell depletion with inebilizumab reduces flare risk in IgG4-RD
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WASHINGTON — Inebilizumab is safe and effective in IgG4-related disease, significantly reducing the chance of flare through 52 weeks compared with placebo, according to data presented at ACR Convergence 2024.
“This trial, a culmination of 15 years on the concept that B-cell depletion might be an important therapeutic approach to the treatment of IgG4-related disease (IgG4-RD), is a response to the massive unmet medical need in this disease,” John H. Stone, MD, MPH, professor of medicine at Harvard Medical School, told Healio. “Although IgG4-RD is a disease that occurs all over the world and affects humans across the spectrum of age, it is a condition that targets middle-aged to elderly individuals and tends to damage the pancreas partly hard.
“For this reason, it is essential to develop therapies other than glucocorticoids for this disease,” he added.
To examine the efficacy and safety of inebilizumab (Uplizna, Amgen) for reducing flare risk in adults with IgG4-RD, Stone and colleagues conducted the phase 3 MITIGATE trial. The results were published in the New England Journal of Medicine.
According to Stone, who presented the findings, MITIGATE was the first randomized, double-blind, placebo-controlled study ever conducted in IgG4-RD. The study enrolled 135 adults with IgG4-RD at 80 sites across 22 countries. The participants were randomly assigned to receive either 300 mg of inebilizumab (n = 68) or a placebo (n = 67) on day 1, day 15, and week 26 of the 52-week study.
Corticosteroid regimens were set at 20 mg of prednisone per day at the time of assignment and subsequently tapered down to discontinuation at the end of week 8. The primary endpoint was the time to first IgG4-RD flare, as determined by an adjudication committee and treated by Stone and colleagues.
Compared with placebo, inebilizumab significantly reduced the risk for flare (HR = 0.13; 95% CI, 0.06-0.28), according to the researchers. Stone and colleagues additionally reported statistically significant effects in favor of inebilizumab across all secondary endpoints, including annualized flare rate as well as the proportion of patients who achieved flare- and treatment-free complete remission, or corticosteroid-free complete remission, at week 52.
Meanwhile, 97.1% of inebilizumab-treated patients, and 98.5% of placebo-treated patients, reported at least one treatment-emergent adverse event (TEAE) (n = 66 for both). The most frequently reported TEAEs were COVID-19, lymphopenia and urinary tract infection. No patients died, and no serious adverse events occurred in more than one participant, according to the researchers.
“The results confirm beyond doubt that B-cell depletion is an effective treatment strategy,” Stone said. “B-cell depletion with inebilizumab reduced the likelihood of disease flare by 87%, compared to a standard regimen of glucocorticoids. The great majority of patients in the inebilizumab group were able to maintain their disease remissions throughout the follow-up period without additional steroids.”
According to Stone, the goal now is to develop “therapies that are equally effective but more readily reversible” than B-cell depletion.
“It will be critical to consider other pathways for targeting and to contemplate therapies that are directed specifically toward the fibrosis, which is such a universal characteristic of IgG4-RD,” he said.
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Stone J. Abstract #0775. Presented at: ACR Convergence 2024; Nov. 14-19, 2024; Washington, D.C.
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