Long-term use of Uplizna cuts flares, need for steroids in those with IgG4-RD
Added data from MITIGATE trial also sheds new light on rare disease
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Long-term use of the approved infusion therapy Uplizna (inebilizumab) leads to lasting cuts in flares, or periods of symptom worsening, in adults with active IgG4-related disease (IgG4-RD).
That’s according to the first year of data from an open-label extension (OLE) portion of the Phase 3 MITIGATE clinical trial (NCT04540497), which is testing the therapy, administered every six months, in more than 100 adults with active IgG4-RD. The OLE is designed to span three years of treatment.
For most individuals taking part, the data also show that treatment with Uplizna resulted in high rates of complete, glucocorticoid-free remission — meaning patients did not need standard glucocorticoid treatment to control symptoms or prevent flares, which can lead to possible organ damage. Glucocorticoids are a type of corticosteroid, a class of steroid hormones, and are associated with serious side effects when used over a long period or at high doses.
“IgG4-RD is a chronic, debilitating disease marked by recurrent, unpredictable flares that can potentially impact multiple organs,” Sumita Bhatta, vice president and global development therapeutic area head of rare disease at Amgen, the therapy’s developer, said in an emailed statement to IgG4-Related Disease News regarding the new data.
These “MITIGATE results further [support] the longer-term clinical profile and sustained results of Uplizna” as a treatment for IgG4-RD, Bhatta said.
The MITIGATE OLE data were presented at the European Alliance of Associations for Rheumatology (EULAR) 2026 Congress, held earlier this month in London. The poster was titled “Long-term Efficacy and Safety of Inebilizumab in IgG4-Related Disease: Primary Results from Year 1 of the Open-Label Period (OLP) of the Phase 3 MITIGATE Trial.”
IgG4-RD is an immune-mediated disorder marked by abnormal clumps of immune cells, inflammation, and scarring in tissues. The disease, which can affect virtually any organ and tissue in the body, typically follows a relapsing course, meaning patients experience recurring flares, or episodes of active disease, that can damage organs and reduce quality of life.
No flares seen for trial participants always on Uplizna
Uplizna, given via intravenous, or into-the-vein, infusions, is approved in the U.S. for adults with IgG4-RD. The therapy works by killing CD19-positive B-cells, a type of immune cell that, in IgG4-RD, forms clumps in tissues and secretes large amounts of an antibody type called IgG4.
Its approval in the U.S. last year was supported by results from the one-year placebo-controlled portion of MITIGATE, which enrolled 135 adults with active IgG4-RD.
Compared with the placebo, Uplizna significantly reduced the risk of confirmed, treated flares by 87%. Additionally, more than twice as many Uplizna-treated patients achieved complete remission without glucocorticoids or flares.
Nearly 80% of participants who completed the trial’s placebo-controlled portion entered the OLE phase, in which all were given Uplizna on day 1. These individuals then received either the therapy or a placebo on day 15, depending on their previously assigned treatment. All then received Uplizna every six months.
Of the 107 OLE participants, 51 were originally assigned the placebo — and thus were dubbed the switch group — while 56 were originally assigned Uplizna (the Uplizna group). Over a median of 2.2 years, participants received a median of six Uplizna infusions, according to the researchers.
During the OLE’s first year, no participant in the Uplizna group and three participants (6%) in the switch group experienced a confirmed, treated flare. Those three flares occurred within the first five months of the OLE, the data showed.
For context, during the one-year placebo-controlled phase, 9% of patients on Uplizna and 57% of those on the placebo had experienced flares.
These findings may help clinicians identify opportunities for earlier intervention and reduce avoidable flares.
Also, at one year, 71% of people always on Uplizna and 41% in the switch group achieved flare-free, glucocorticoid-free complete remission, meaning they did not take steroids and had no flares. Long-term Uplizna treatment was also associated with fewer patients on glucocorticoids and lower doses of these medications.
Additionally, B-cell counts and IgG4 levels in the blood remained low with continued Uplizna treatment, the researchers noted.
Consistent with Uplizna’s established safety profile, the most commonly reported adverse events were COVID-19, upper respiratory infection, cough, and influenza. No new safety signals were reported with longer treatment.
“For clinicians, a sustained reduction in flares and timely intervention are central to improving long-term outcomes,” John Stone, MD, MITIGATE’s principal investigator, said in an Amgen press release. Stone is a professor of medicine at Harvard Medical School and the Edward A. Fox chair in medicine at the Massachusetts General Hospital.
According to Stone, “these findings may help clinicians identify opportunities for earlier intervention and reduce avoidable flares.”
Organ involvement ‘complex’ in untreated IgG4-RD
At EULAR, the researchers also used trial data — from MITIGATE’s first part — to provide new insights into the natural history of IgG4-RD. That data came from the 67 participants given the placebo.
The poster for that oral presentation was titled “Natural History of IgG4-RD: Patterns of Organ Involvement and Flare-associated Biomarker Changes in the Phase 3 MITIGATE Trial.”
More than half of these participants — 60% — experienced one or more flares that required treatment, the data showed. The researchers analyzed affected organs at three points: historic flares before the trial, at the study’s start, or baseline, and during the study.
The patterns of organ involvement in this group were described as “complex” and varying by organ. In one example, participants with involvement of lymph nodes (immune structures across the body) in their baseline flare showed widespread and diverse organ involvement in their history and involvement of multiple other organs at the study’s start. These individuals were found to have involvement of new organs in subsequent flares.
To identify how various biomarkers changed during in-study flares, the researchers analyzed blood samples collected over six months before and after each flare. Within 30 days before a flare, CD19-positive B-cells were the first to rise, followed by increases in total IgG, the antibody class IgG4 belongs to, and its specific subsets, including IgG4.
In a third poster, the researchers showed that the development of antibodies against Uplizna during MITIGATE’s placebo-controlled part did not affect the treatment’s effectiveness or its movement into, through, and out of the body.
Lastly, scientists showed in a fourth poster that, despite mild reductions in certain protective antibodies for up to four years on Uplizna during MITIGATE, there was no increased infection risk, and infection rates did not increase over time.
These data all contribute to scientists’ knowledge of IgG4-RD, Bhatta said.
“At the EULAR 2026 Congress, Amgen presented new data that advanced understanding of IgG4-RD and reinforced the importance of sustained disease control,” Bhatta said.
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