Biomarkers may predict response to off-label treatment in IgG4-RD
Study finds diverse patient group shows similar disease patterns
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Lower relative levels of antibodies commonly found in immunoglobulin G4-related disease (IgG4-RD) and the absence of symptoms affecting the eyes and tear glands may help predict better response to off-label treatment with rituximab, according to a study in the U.S.
Data also showed that while IgG4-RD appears to affect patients of all races and ethnicities similarly, not all have access to the same type of treatment.
“This study aims to provide insights into personalized treatment strategies and inform future research for optimizing IgG4-RD management in diverse populations,” researchers wrote.
The study, “IgG4-to-IgG Ratio and Orbital Involvement Predict Clinical Response to B Cell Depletion in IgG4-Related Disease,” was published in ACR Open Rheumatology. It drew on data from IgG4-RD patients in Long Island, New York.
Study explored how disease manifests in different racial, ethnic groups
IgG4-RD occurs when immune cells, including B-cells producing a type of antibody called IgG4, cause long-lasting inflammation in different tissues of the body, leading to a range of symptoms. While it can affect anyone regardless of racial or ethnic background, differences among diverse populations in the U.S. have not been well studied.
“Understanding these variations is critical for tailoring diagnostic and therapeutic approaches to diverse patient populations, particularly in regions like Long Island, New York, which hosts a racially and ethnically [varied] population,” the researchers wrote.
To better understand how the disease manifests in different racial and ethnic groups and to identify factors that may predict response to treatment, the researchers reviewed existing medical records from 58 IgG4-RD patients.
All were treated at Northwell Health in New York between 2011 and 2023. Their mean age was 62.7 years, and more than half (56.9%) were men. A total of 25 people (43.1%) were white, 14 (24.1%) were Asian, 11 (19%) were Hispanic, and eight (13.8%) were Black.
Racial disparities observed regarding treatment access
Overall, the disease affected all groups similarly. The most commonly affected tissues were the lymph nodes, which are immune structures located throughout the body (22.4%). This was followed by involvement of the tissues around the eyes and tear glands (20.7%) and the retroperitoneum, the area in the back of the abdomen that includes the kidneys and the body’s largest blood vessel (20.7%).
Blood IgG4 levels were higher than normal in 42.9% of patients, also without significant differences between racial/ethnic groups.
The high overall favorable response rate (87.9%) across racial groups, despite variations in treatment approaches, supports the concept that IgG4-RD management can be individualized based on disease [profile], patient preferences, and local resources.
Most patients (82.8%) received glucocorticoids, a potent anti-inflammatory medication that is the first-line treatment for IgG4-RD. More than half (60.3%) received rituximab. Marketed as Rituxan and Mabthera, with biosimilars available, rituximab works by killing B-cells. None of the treatments are specifically approved for IgG4-RD, but are often used off-label.
“Striking racial disparities in rituximab use were observed,” the researchers wrote. Specifically, none of the Black patients received rituximab, compared with 57.1% to 76% of those in the other racial/ethnic groups.
Despite differences in treatment, favorable clinical responses were common across all groups. A favorable response was defined as an IgG4-RD Responder Index score of zero or one, indicating little or no active disease.
Favorable treatment responses occurred in most patients, including white (92%), Asian (78.6%), Black (100%), and Hispanic (81.8%), with no significant differences between groups.
“The high overall favorable response rate (87.9%) across racial groups, despite variations in treatment approaches, supports the concept that IgG4-RD management can be individualized based on disease [profile], patient preferences, and local resources,” the researchers wrote.
Patients with eye involvement less likely to respond to rituximab
The researchers also investigated potential predictors of response to rituximab.
The average ratio of IgG4 to total IgG (IgG4’s broader antibody class) in the blood decreased significantly from 0.113 to 0.097 after rituximab treatment, suggesting a reduction in IgG4 levels. Specifically, the ratio decreased by 0.029 in patients who responded to rituximab but increased by 0.010 in those who did not respond.
Statistical analyses showed that the change in the IgG4-to-IgG ratio was better at predicting response to rituximab than the starting ratio. The ratio change allowed researchers to discriminate responders from nonresponders with an accuracy of 80.6%, while the starting ratio was associated with an accuracy of 55%.
In addition, patients with involvement of the tissues around the eyes and tear glands were significantly more likely, by more than 6.5 times, to fail to respond to rituximab.
“This observation has important clinical implications because patients presenting with [eye-related] manifestations may require more aggressive monitoring or alternative treatment approaches,” the team wrote.
However, because only four patients did not respond to rituximab, the researchers emphasized that these findings need confirmation in larger studies.
“This study provides a comprehensive examination of IgG4-RD in a racially and ethnically diverse Long Island [group of patients],” the researchers wrote. “These findings warrant further investigation into potential socioeconomic and health care access factors influencing treatment selection.”
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