First‐Year IgG Dynamics in IgG4 ‐Related Disease: A Critical Window for Predicting Long‐Term Outcomes

OBJECTIVE: To investigate longitudinal serum IgG dynamics in IgG4-related disease (IgG4-RD) after treatment and assess their prognostic value for relapse. METHODS: A retrospective cohort of 274 newly treated patients with IgG4-RD was stratified into elevated IgG (n = 186) and normal IgG (n = 88) groups. Treatment responses were evaluated by covariance analysis adjusted for baseline IgG. Longitudinal IgG trends and relapse risk were analyzed using Kaplan-Meier curves and Cox regression. RESULTS: Elevated baseline IgG level was associated with more severe phenotypes, including male predominance, older age, higher responder index scores, more internal organ involvement, hypocomplementemia, and elevated erythrocyte sedimentation rate/C-reactive protein level. IgG1 and IgG4 mainly contributed to IgG elevation. After treatment, 79.6% of patients with elevated IgG levels achieved normalization, with the greatest decline in the first year. Glucocorticoid (GC)-based regimens reduced IgG levels more effectively than GC-sparing therapies and achieved higher normalization rates (85.2% vs 66.7%). Twelve-month IgG normalization strongly predicted reduced relapse risk. Patients achieving IgG normalization had lower relapse rates (17.9% vs 44.1%; P = 0.001) and superior relapse-free survival (mean 33.20 [95% CI 32.21-34.19] vs 27.71 [95% CI 24.29-31.13] months; log-rank P < 0.001). Multivariate Cox regression confirmed failure of 12-month IgG normalization (hazard ratio [HR] 2.67 [95% CI 1.43-4.99], P = 0.002) and treatment intensity (GCs + weak immunosuppressants [IMs]: HR 0.36, P = 0.012; GCs + potent IMs: HR 0.40, P = 0.020, vs GC-sparing) as independent relapse determinants. CONCLUSION: Baseline IgG elevation marks more severe IgG4-RD phenotypes. The first treatment year achieving IgG normalization represents a critical prognostic biomarker. Failure to normalize IgG within 12 months markedly increases relapse risk. Longitudinal IgG monitoring supports risk stratification and treatment optimization.