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 RA B-Cell DepletionClifton Bingham, M.D. - Jon Giles, M.D. Abstract 1234: Vaccination Against Influenza in Rheumatoid Arthritis Patients: The effect of Rituximab on the Humoral ResponseThe potential for rituximab therapy, via depletion of B cells, to interfere with the maintenance of protective immunity or diminish the de novo response to vaccination has not been definitively evaluated. Here, Oren et al investigate vaccine responses to influenza vaccine in RA subjects treated with rituximab. Methods Three groups of patients were enrolled:
All subjects received inactivated trivalent influenza vaccine via subcutaneous injection at baseline. Protective antibody status was assessed at baseline and after 6 weeks, with response defined as a > four-fold rise in antibody titers for each of the 3 influenza strains covered by the vaccine (Shanghai, New Caledonia, and California), or seroconversion in those without evidence of protective antibodies at baseline. Results Compared to the subjects in the non-biologic DMARD group, those receiving rituximab tended to be older (64 vs. 53 years, respectively), with a higher proportion of males (24% vs. 7%, respectively), and a higher proportion of subjects receiving current glucocorticoids (50% vs. 23%, respectively). RA disease duration and methotrexate use were similar between groups. A mean of 32 ± 22 weeks had passed since rituximab treatment. In contrast, mean age in the control population was 58 years with 67% of subjects being female. Compared to RA subjects receiving non-biologic DMARDs and non-RA controls, vaccine response levels were similar in rituximab treated subjects for Shanghai and New Caledonia antigen, but not California antigen. Among rituximab treated subjects, there was no significant correlation between circulating B cell levels or time since last rituximab infusion on level or specificity of antibody response achieved after vaccination. Among all RA subjects, there was no significant correlation between demographic or RA treatment factors and vaccine response. Vaccination did not appear to have any effect on parameters of RA disease activity in either group of RA subjects. Conclusions Although humoral responses may be decreased for specific antigens, overall humoral responses were comparable in rituximab treated subjects to those in RA subjects not treated with biologic DMARDs or non-RA controls. Influenza vaccination does not appear to have an adverse affect on RA disease outcomes. Editorial Comment These results are encouraging, as rituximab is the biologic DMARD with the greatest potential to alter established protective humoral immunity and hinder de novo vaccine response. However, several questions remain unanswered by the abstract presented here. For one, the authors did not reveal how many prior courses of rituximab had been used in the rituximab treated subjects, although presumably the number of treatment courses was low. It is possible, owing to the potential for accumulated suppressive effects on B cells over time, that a diminished vaccine response will only be detected after multiple treatment courses. Another unanswered question is whether vaccination prior to rituximab treatment is preferable to after treatment, recognizing that influenza vaccine is seasonal and may not be amenable to waiting for available vaccine in most patients. It may be possible, with further investigation, to identify subsets of RA patients who are candidates for an increased inoculum load or a booster dose in order equalize acquired immune responses. In addition, humoral responses to other vaccines, primarily pneumococcus and hepatitis A and B, may be individually affected and require separate evaluation.
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