Abstract: SA-PO0682
Patterns of Kidney Involvement in the Phase 3 MITIGATE Trial of Inebilizumab in IgG4-Related Disease (IgG4-RD)
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - Other
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Radhakrishnan, Jai, Columbia University, New York, New York, United States
- Stone, John H., Harvard Medical School, Boston, Massachusetts, United States
- Culver, Emma L., University of Oxford, Oxford, England, United Kingdom
- Khosroshahi, Arezou, Emory University, Atlanta, Georgia, United States
- Zhang, Wen, Peking Union Medical College Hospital, Beijing, China
- Della Torre, Emanuel, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Okazaki, Kazuichi, Kansai Ika Daigaku Kori Byoin, Neyagawa, Osaka Prefecture, Japan
- Tanaka, Yoshiya, University of Occupational and Environmental Health, Kitakyushu, Japan
- Löhr, Matthias, Karolinska Institutet, Stockholm, Stockholm County, Sweden
- Schleinitz, Nicolas, Aix-Marseille Universite, Marseille, Provence-Alpes-Côte d'Azur, France
- Dong, Lingli, Tongji Hospital Department of Hematology, Wuhan, Hubei, China
- Umehara, Hisanori, Nagahama City Hospital, Shiga, Japan
- Lanzillotta, Marco, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Wallace, Zachary, Amgen Inc, Thousand Oaks, California, United States
- Ebbo, Mikael, Aix-Marseille Universite, Marseille, Provence-Alpes-Côte d'Azur, France
- Martinez Valle, Fernando, Internal Medicine Department, Vall d'Hebron Hospital, Barcelona, Spain
- Alexander, Theresas A., Amgen Inc, Thousand Oaks, California, United States
- Clarkson, Kristen, Amgen Inc, Thousand Oaks, California, United States
- Nayar, Manu, Hepato-Pancreato-Biliary Unit, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- Rebours, Vinciane, Pancreatology and Digestive Oncology Department, Beaujon Hospital, AP-HP, Clichy, Universite Paris-Cite, France
- Luo, Rong, Amgen Inc, Thousand Oaks, California, United States
- Cheng, Sue, Amgen Inc, Thousand Oaks, California, United States
- Rosen, Melissa, Amgen Inc, Thousand Oaks, California, United States
- Cimbora, Daniel, Amgen Inc, Thousand Oaks, California, United States
Background
IgG4-RD is a fibroinflammatory multiorgan disease in which kidney involvement can drive irreversible loss of renal function if unrecognized. The MITIGATE trial demonstrated the safety and efficacy of inebilizumab (a CD19-targeted B-cell depleting agent) in IgG4-RD. We analyzed flare patterns of organ involvement and biomarker changes in the placebo (PBO) group in MITIGATE patients (pts) with kidney or retroperitoneal disease activity.
Methods
MITIGATE enrolled 135 pts with multiorgan IgG4-RD and a recent flare needing glucocorticoid treatment. Pre-study, baseline (BL), and on-study flares in the PBO arm (n=67) were analyzed to characterize patterns of organ involvement. Changes in blood and urine biomarkers relative to time of flare (defined as treatment start date) were analyzed.
Results
40/67 (59.7%) PBO pts experienced ≥1 on-study flare(s) during the 52-week randomized controlled period. Among 19 pts with BL kidney involvement, 12 (63.2%) experienced an on-study flare. Patterns of organ involvement were complex and dynamic in pts with BL kidney involvement (Figure). Particularly interesting are cases of de novo activity in previously unaffected organs, and complex patterns of co-involvement organs. Findings in pts with BL retroperitoneal involvement are similar. Biomarker changes around the time of on-study flares affecting the kidney showed patterns indicative of impending flare, organ dysfunction at the time of flare, and apparent response to treatment. CD19+ B cells increased first prior to kidney flare, followed by increases in total IgG and IgG subsets IgG1, IgG2, IgG3, and IgG4 within the 30-day window preceding a flare. Lab values were indicative of kidney dysfunction around the time of kidney flares and normalized following flare treatment.
Conclusion
The complex and dynamic patterns of affected organs in IgG4-RD patients with kidney involvement emphasize the need for diligence in assessing patients with this disease. Markers, including B cells and immunoglobulins, may serve as useful predictors of impending disease flares in these patients.
Acknowledgment
Study and abstract were funded by Amgen Inc. with medical writing support provided by Swati Ghatpande, PhD and Deepa Mothey, PhD of Amgen, Inc.
Funding
- Commercial Support – Amgen