IgG4 ‐to‐ IgG Ratio and Orbital Involvement Predict Clinical Response to B Cell Depletion in IgG4 ‐Related Disease

Objective

IgG4‐related disease (RD) demonstrates ethnic variations in phenotype, but data from diverse US populations are limited. We characterized ethnic differences in organ involvement and evaluated predictors of treatment response in a multiethnic cohort.

Methods

We conducted a retrospective study of 58 patients meeting 2019 American College of Rheumatology/EULAR criteria at Northwell Health (2011–2023). Data on demographics, organ involvement, histopathology, treatment, and serology (IgG4‐to‐IgG ratios) were analyzed. Response was assessed using Carruthers’ Index.

Results

The cohort included 43.1% White, 24.1% Asian, 19.0% Hispanic, and 13.8% Black patients. Organ involvement patterns were consistent across races, with lymph nodes (22.4%), orbital/lacrimal (20.7%), and retroperitoneum (20.7%) being most affected. Higher disease burden was observed in Asian patients (1.93 vs 1.44–1.64 organs, P  = 0.058). A striking disparity in rituximab use was observed (0% in Black patients vs 57%–76% in others, P  = 0.002), whereas disease phenotype distribution was otherwise similar across groups. Favorable response rates were high and comparable across all racial and ethnic groups (78.6%–100%, P  = 0.462). In patients treated with rituximab (n = 35), a reduction in IgG4‐to‐IgG ratio predicted response (area under the curve = 0.806), outperforming baseline ratios. Orbital/lacrimal involvement was strongly associated with treatment failure (75% of nonresponders vs 13.3% of responders; odds ratio 6.6, 95% confidence interval 1.4–31.9, P  = 0.03).

Conclusion

In a diverse IgG4‐RD cohort, disease phenotypes were consistent across races, though treatment access disparities existed. Dynamic changes in IgG4‐to‐IgG ratios and the presence of orbital disease are key predictors of response to rituximab, informing personalized treatment strategies.

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