RESEARCH - Immunization responses in RA patients treated with rituximab

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Arthritis Rheum. 2009 Dec 28;62(1):64-74.

Immunization responses in rheumatoid arthritis patients treated with

rituximab: Results from a controlled clinical trial.

Bingham CO 3rd, Looney RJ, Deodhar A, Halsey N, Greenwald M, Codding

C, Trzaskoma B, F, Agarwal S, Kelman A.

s Hopkins University, Baltimore, land.

OBJECTIVE: To examine immunization responses in patients with

rheumatoid arthritis (RA) treated with rituximab and to investigate

the effects of rituximab-induced CD20+ B cell depletion on immune

responses to tetanus toxoid (T cell-dependent antigen), pneumococcal

polysaccharide (T cell-independent antigen), and keyhole limpet

hemocyanin (KLH) (neoantigen) and on delayed-type hypersensitivity

(DTH).

METHODS: In a controlled trial, we enrolled 103 patients with active

RA receiving a stable dose of methotrexate (MTX). Tetanus toxoid,

pneumococcal polysaccharide, and KLH vaccines as well as a Candida

albicans skin test were administered to 1 group of patients receiving

rituximab plus MTX (called rituximab-treated patients) for 36 weeks

and to 1 group of patients receiving MTX alone for 12 weeks. The

primary end point was the proportion of patients with a >/=4-fold rise

in antitetanus IgG levels. Antitetanus, antipneumococcal, and anti-KLH

serum IgG levels were measured prior to and 4 weeks following vaccine

administration. The DTH response to C albicans was measured 2-3 days

following placement.

RESULTS: Responses to tetanus toxoid vaccine (>/=4-fold rise) were

similar in both groups (39.1% of rituximab-treated patients and 42.3%

of patients treated with MTX alone). The ability to maintain a

positive DTH response to the C albicans skin test was comparable in

both groups (77.4% of rituximab-treated patients and 70% of patients

treated with MTX alone), showing no effect of rituximab treatment.

Rituximab-treated patients had decreased responses to pneumococcal

polysaccharide vaccine (57% of patients had a 2-fold rise in titer in

response to >/=1 serotype, compared with 82% of patients treated with

MTX alone) and to KLH vaccine (47% of patients had detectable anti-KLH

IgG, compared with 93% of patients treated with MTX alone).

CONCLUSION: Recall responses to the T cell-dependent protein antigen

tetanus toxoid as well as DTH responses were preserved in

rituximab-treated RA patients 24 weeks after treatment. Responses to

neoantigen (KLH) and T cell-independent responses to pneumococcal

vaccine were decreased, but many patients were able to mount

responses. These data suggest that polysaccharide and primary

immunizations should be administered prior to rituximab infusions to

maximize responses.

PMID: 20039397

http://www.ncbi.nlm.nih.gov/pubmed/20039397

Not an MD