Treatment may lower disease flare risk for some IgG4-RD patients

The approved therapy Uplizna (inebilizumab) may reduce the risk of disease flares in adults with IgG4-related disease (IgG4-RD) who have kidney involvement, according to a new analysis of clinical trial data.

The new analysis focuses on a subgroup of patients in the Phase 3 MITIGATE clinical trial (NCT04540497), top-line data from which formed the basis for Uplizna’s approval in the U.S. as a treatment for adults with IgG4-RD.

Amgen, which markets Uplizna, shared the new subgroup findings at the American Society of Nephrology’s Kidney Week 2026, held last week in Denver.

Results in the subgroup of patients with kidney involvement “were very consistent” with those seen in the overall trial population, Jai Radhakrishnan, MD, a kidney disease specialist and professor of medicine at Columbia University Irving Medical Center, said in written Q&A with IgG4-RD News.

“Patients on Uplizna had nearly identical lower flare rates and remission rates irrespective of kidney involvement,” said Radhakrishnan, who presented the analysis at the meeting.

IgG4-RD is a chronic immune disease marked by abnormal clumps of immune cells, particularly B-cells producing a type of antibody called IgG4. The disease can affect various organs throughout the body, including the kidneys.

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‘Silent’ kidneys

“Kidney involvement is often silent, with … few symptoms, and when it is found it can look like lupus, lymphoma [a type of blood cancer], infection, or even kidney cancer,” making it hard to diagnose and manage, Radhakrishnan said.

Glucocorticoids, a type of anti-inflammatory and immunosuppressive medication, are the first-line treatment for IgG4-RD. While these therapies can help prevent disease relapses (periods of worsening disease activity), they can cause problematic side effects if used long term. This poses complex challenges for patients with kidney involvement, Radhakrishnan said.

In these patients, “management is difficult because most … relapse when [glucocorticoids] are tapered, and long-term [glucocorticoid] use is hard on this older population,” he said.

At the same time, preventing relapses, also known as flares, is crucial because “repeated flares can cause permanent scarring in the kidney,” Radhakrishnan said.

Uplizna, which works to kill B-cells by targeting a protein at their surface, CD19, was the first IgG4-RD treatment to win U.S. approval. The therapy is administered via infusion into the bloodstream, two weeks apart for the first two doses and every six months thereafter.

The one-year MITIGATE trial tested Uplizna against a placebo in more than 130 adults with active IgG4-RD, with results demonstrating that the therapy significantly reduced the risk of confirmed, treated flares by 87%.

Now, researchers presented outcomes from the subset of trial participants who had kidney involvement: 21 in the Uplizna group and 19 in the placebo group. Confirmed, treated relapses occurred in two participants given Uplizna (9.5%) and 12 of those on the placebo (63.2%), resulting in a significantly lower risk, by 92%, with Uplizna.

None of the flares in the Uplizna group involved the kidneys, while three flares in the placebo group did.

“Repeated flares can lead to scarring and chronic kidney disease, so preventing them should help preserve kidney function,” Radhakrishnan said.

On average, the yearly flare rate was 0.09 with Uplizna and 0.91 with the placebo. And more than half (57.1%) of participants treated with Uplizna achieved flare-free, glucocorticoid-free complete remission (no signs or symptoms), compared with less than one-quarter (21.1%) of participants on the placebo.

By achieving this outcome, “patients avoid the effects of long-term [glucocorticoids], such as weight gain, poor sleep, mood changes, high blood sugar, bone loss, and infections,” Radhakrishnan said.

“Fewer flares also mean fewer courses of high-dose [glucocorticoids],” he added. Indeed, participants treated with Uplizna received significantly lower total doses of glucocorticoids (58 vs. 1,755 mg), representing a more than 30 times reduction in glucocorticoid use with the therapy.

These results were generally in line with those reported in the overall population. Annual flare rates were 0.1 with Uplizna and 0.71 with the placebo, and the proportion of participants who attained glucocorticoid-free complete remission was 58.8% with Uplizna and 22.4% with the placebo.

“Placebo patients with kidney involvement flared somewhat more often and sooner than the overall placebo group, suggesting they may be at higher risk,” Radhakrishnan said. Still, he added, the data suggest that “the benefit of Uplizna was at least as large” among patients with kidney involvement.

Safety data from the subgroup of patients with kidney involvement were also “consistent with the overall trial, with the drug being well tolerated and no deaths and no new safety signals,” Radhakrishnan said.

Because this was a short-term analysis limited to a few dozen patients, the results should be “considered supportive rather than definitive,” Radhakrishnan said, adding that “longer follow-up will be needed to confirm the effect on long-term kidney outcomes.”