Inebilizumab reduces flare risk in IgG4-RD patients across demographics

Treatment with inebilizumab reduced the risk of disease flares in patients with immunoglobulin G4-related disease (IgG4-RD) irrespective of sex, age, or race, according to a subgroup analysis of the phase III MITIGATE study presented at EULAR 2025.

This analysis included 135 patients with Ig-G4-RD (median age 58.2 years, 47 percent male), of whom 46.7 percent were Asians, 39.3 percent were White, and 14.1 percent belonged to other races. Patients had been receiving glucocorticoid treatment for 3–8 weeks prior to randomization.

Participants were randomly assigned to receive either intravenous infusions of inebilizumab 300 mg on days 1 and 15 and week 26 (n=68) or placebo (n=67) for 52 weeks. Both arms received identical glucocorticoid tapers, with 5 mg/day every 2 weeks until discontinuation after 8 weeks. [EULAR 2025, abstract OP0189]

At week 52, patients treated with inebilizumab had a reduced risk of treated and adjudicated IgG4-RD flares than those treated with placebo in both females (3 vs 10 [number of flares]; hazard ratio [HR], 0.16; p=0.0052) and males (4 vs 30; HR, 0.12; p<0.001).

Similar results were seen between inebilizumab-treated patients aged <65 (6 vs 30 [number of flares]; HR, 0.14; p<0.001) and ≥65 (1 vs 10; HR, 0.09; p=0.0205) years compared with placebo-treated patients.

In terms of race, patients in the inebilizumab group also showed a reduced risk of treated and adjudicated IgG4-RD flares vs those in the placebo group in both the Asian (4 vs 13 [number of flares]; HR, 0.12; p<0.001) and White (2 vs 20; HR, 0.13; p=0.0059) cohorts.

“Inebilizumab provides benefits in IgG4-RD treatment across demographic subgroups compared with placebo,” said lead author Dr John Stone from Massachusetts General Hospital in Boston, Massachusetts, US.

Key secondary endpoints

By week 52, the overall annualized flare rate was numerically lower in the inebilizumab arm than the placebo arm, irrespective of sex, age, or race (rate ratio, 0.14; p<0.001).

More patients on inebilizumab were flare-free and achieved glucocorticoid-free complete remission* across all demographic subgroups at week 52 compared with those on placebo (odds ratio, 4.96; p<0.001).

Furthermore, the total glucocorticoid use per participant for IgG4-RD flare or maintenance was numerically lower with inebilizumab compared with placebo, regardless of sex, age, race, or geographic region (least squares mean difference, -1,264 mg; p<0.0001).

“Participants who received inebilizumab required less cumulative glucocorticoid exposure to induce remission and maintain disease control during the treatment period than participants who received placebo,” noted the researchers. [N Engl J Med 2025;392:1168-1177]

Overall, “efficacy results [and safety findings] in all subgroups were consistent with the overall trial population,” stated Stone.

“These findings indicate that inebilizumab may be a safe and efficacious option for the treatment of IgG4-RD in all demographic subgroups,” he added.