The effect of rituximab on vaccine responses in patients with immune thrombocytopenia

• Published in: Blood Vol. 122; no. 11; pp. 1946 - 1953
• Main Authors: Nazi, Ishac, Kelton, John G., Larché, Mark, Snider, Denis P., Heddle, Nancy M., Crowther, Mark A., Cook, Richard J., Tinmouth, Alan T., Mangel, Joy, Arnold, Donald M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.09.2013
• Subjects: Adult; Aged; Antibodies, Bacterial - immunology; Antibodies, Monoclonal, Murine-Derived - therapeutic use; B-Lymphocyte Subsets - drug effects; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; Bacterial Capsules - immunology; Combined Modality Therapy; Double-Blind Method; Drug Therapy, Combination; Female; Haemophilus influenzae type b - immunology; Haemophilus Vaccines - immunology; Haemophilus Vaccines - therapeutic use; Humans; Immunity, Cellular - drug effects; Immunity, Cellular - immunology; Interferon-gamma - immunology; Interferon-gamma - metabolism; Male; Middle Aged; Prospective Studies; Rituximab; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Thrombocytopenia - drug therapy; Thrombocytopenia - immunology; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-04-494096

B-cell depletion may impair vaccine responses and increase infection risk in patients with immune thrombocytopenia (ITP). We investigated the effects of rituximab on antibody and cellular responses to Streptococcus pneumoniae polysaccharide and Haemophilus influenzae type b (Hib) vaccines in ITP patients. Of 60 patients in the main trial, 24 patients received both vaccines 6 months after rituximab (n = 17) or placebo (n = 7). Among 20 evaluable patients, 3 of 14 (21%) in the rituximab group and 4 of 6 (67%) in the placebo group achieved a fourfold increase in anti-pneumococcal antibodies (P = .12). For anti-Hib antibodies, 4 of 14 (29%) and 5 of 6 (83%), respectively, achieved a fourfold increase (P < .05). Fewer patients in the rituximab group demonstrated Hib killing (2 of 14 [14%], 5 of 6 [83%], P < .05). Three of 14 rituximab-treated patients failed to respond to vaccines by any criteria. After vaccinations, preplasma cell blasts and interferon-γ–secreting T cells were reduced in rituximab-treated patients. Antibody responses were impaired for at least 6 months after rituximab. Cellular immunity was reduced in parallel with depleted B-cell pools. These findings have implications for the timing of vaccinations and the mechanism of infection after rituximab in ITP patients. •After treatment with rituximab, immunological responses to both polysaccharide and conjugated vaccines are impaired in patients with ITP.•Splenectomized patients who received rituximab may be at increased risk of infection because of compromised immune responses to vaccines.