RESEARCH - Highly sensitive B cell analysis predicts response to rituximab therapy in RA

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Arthritis Rheum. 2008 Sep 29;58(10):2993-2999.

Highly sensitive B cell analysis predicts response to rituximab

therapy in rheumatoid arthritis.

Dass S, Rawstron AC, Vital EM, Henshaw K, McGonagle D, Emery P.

University of Leeds, Leeds, UK.

OBJECTIVE: In rheumatoid arthritis (RA), B cell depletion occurs in

all patients treated with rituximab, but the clinical responses to

rituximab are variable. A highly sensitive assay was used to test the

hypothesis that B cell depletion is variable, and that incomplete

depletion leads to a poorer outcome.

METHODS: Sixty patients with active RA unresponsive to anti-tumor

necrosis factor agents received two 1-gram infusions of rituximab. B

cell numbers were measured by highly sensitive flow cytometry before

and after each infusion and at 3-month intervals thereafter. A

reduction in B cell levels below 0.0001 x 10(9)/liter was defined as

complete depletion (compared with 0.05 x 10(9)/liter by conventional

cytometry). Clinical responses were measured using the European League

Against Rheumatism (EULAR) criteria.

RESULTS: At 6 months, 92% of patients had a moderate-to-good clinical

response according to the EULAR criteria. B cells were detected in 63%

of patients after the first infusion of rituximab (median level 0.0009

x 10(9)/liter [range <0.0001-0.0015 x 10(9)/liter), and these patients

had poorer clinical outcomes than patients with complete depletion. At

9 months, 82% of patients with complete depletion had a moderate-to-

good EULAR response, compared with 43% of those with partial depletion

(P = 0.01). At 12 months, 59% of complete responders had a

moderate-to-good EULAR response, compared with 21% of those with

partial depletion (P = 0.01). Patients in whom B cells were depleted

only after the second infusion did no better than those in whom

depletion was never complete and had poorer clinical outcomes than

those in whom depletion was initially complete.

CONCLUSION: This study is the first to show, using a highly sensitive

analysis, that rituximab therapy is associated with variable

diminution in B cell numbers. A lack of complete depletion of B cells

after 1 infusion was associated with a poorer outcome.

PMID: 18821683

http://www.ncbi.nlm.nih.gov/pubmed/18821683

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