Inebilizumab Efficacy and Safety Consistent Across Demographic Subgroups of IgG4-RD

A new post-hoc analysis of the MITIGATE trial, a pivotal trial for the approval of inebilizumab for people with IgG4-related disease (IgG4-RD), supports the use of the therapy across various demographic subgroups of the disease.1

These findings were presented at the European Alliance of Associations for Rheumatology (EULAR) Congress 2025 in Barcelona, Spain, taking place June 11-14, 2025.

“IgG4-RD is a progressive, systemic, fibroinflammatory disease characterized by unpredictable and recurring flares, leading to organ damage and decreased quality of life. The disease can affect nearly any organ,” lead investigators John H. Stone, MD, MPH, principal investigator, and a professor of medicine at Harvard Medical School and Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, and colleagues wrote in their abstract.1

MITIGATE (NCT04540497) is an international, randomized, blinded, placebo-controlled Phase 3 trial that evaluates the safety and efficacy of inebilizumab as treatment for IgG4-RD. Inebilizumab is a humanized, glycoengineered, CD19-directed, B-cell depleting monoclonal antibody that was approved by the FDA under the name Uplizna as the first and only treatment for adult patients with IgG4-RD in April 2025.2

The trial enrolled 135 adult participants who met the ACR/EULAR Classification Criteria for IgG4-RD with a score ≥20 who had a history of multiorgan IgG4-RD and had experienced an IgG4-RD flare that required glucocorticoid treatment during the screening period. The trial stratified participants by first or subsequent IgG4-RD manifestation to account for potential differences in flare risk and randomized them 1:1 to inebilizumab (n = 68) or placebo (n = 67). Treatments took place on day 1, day 15, and week 26 of the 1-year randomized controlled period (RCP).1

The trial’s primary end point was time to first adjudication committee (AC)-determined and investigator-treated IgG4-RD flare during the RCP. It also evaluated key secondary endpoints including annualized flare rate during the RCP and the proportion of participants achieving flare-free, treatment-free complete remission or flare-free, corticosteroid-free complete remission at Week 52. Investigators also evaluated safety.

The trial’s 2 treatment groups had generally well balanced baseline demographics. Participants had a mean age of 58.2 years in the study, with 31.1% of participants aged 65 years or older, and 34.8% of participants were female, consistent with the known male predominance of of IgG4-RD. A total of 46.7% of participants were Asian, 39.3% were White, and 7.4% did not report. The remaining 6.6% of participants consisted of Black, American Indian or Native Alaskan, Native Hawaiian or other Pacific Islander, unknown or other races.

The investigators found that inebilizumab treatment significantly reduced the risk of flare relative to placebo regardless of age, sex, or race, with each subgroup exhibiting a hazard ratio similar to the overall study population, and consistent trends were observed across all regions.

They also found that inebiliuzmab reduced annualized flare rates relative to placebo in all demographic subgroups. Similar results were observed for all subgroups with sufficient representation for the proportion of participants achieving flare-free, treatment-free complete remission or flare-free, corticosteroid-free complete remission at Week 52. Furthermore, safety findings were similar in each subgroup to that observed in the overall population.

REFERENCES

Stone JH, Culver EL, Khosroshahi A, et al. Safety and Efficacy of Inebilizumab in IgG4-Related Disease Across Various Participant Demographics: Subgroup Analysis from the MITIGATE Study. Presented at: EULAR Congress 2025; Barcelona, Spain; June 11-14. Presentation #OP0189