PURPOSE: Siltuximab (IL6 antibody) is approved for the treatment of multicentric 
Castleman disease (MCD). Effects of IL6 inhibition on the inflammatory milieu 
accompanying MCD have not been characterized.
EXPERIMENTAL DESIGN: Trends in inflammatory- and anemia-associated markers, 
measured over the course of a placebo-controlled study of siltuximab (11 mg/kg 
q3w) in patients with MCD (n = 79), were characterized.
RESULTS: Baseline IL6 and C-reactive protein (CRP) levels were significantly 
correlated (r = 0.708; P < 0.0001). CRP levels decreased (median, 92%) by cycle 
1 day 8 (C1D8), remaining suppressed during siltuximab treatment while remaining 
stable in the placebo group. There were no associations between baseline CRP or 
IL6 and MCD symptom burden, histologic subtype, ethnicity, maximum CRP decrease, 
and response parameters. A hemoglobin response (change ≥ 15 g/L at week 13) was 
observed with siltuximab (61%; P = 0.0002). Median hepcidin decrease from 
baseline at C1D8 with siltuximab was 47% versus median 11% increase with 
placebo. Maximum post-baseline changes in hepcidin levels among siltuximab 
recipients were correlated with maximum changes for hemoglobin (r = -0.395; P = 
0.00607), total iron-binding capacity (TIBC; r = -0.354; P = 0.01694), and 
ferritin (r = 0.599; P = 0.0001). Greater median changes from baseline in 
ferritin, hemoglobin, and TIBC were observed in anemic siltuximab-treated 
patients.
CONCLUSIONS: IL6 neutralization with siltuximab resulted in sustained CRP 
suppression and improvement of anemia, in part, by hepcidin pathway inhibition.