OP-0253 – A Single Course of Rituximab does not Abrogate Anti-Infliximab Antibodies in Patients with Rheumatoid Arthritis

van den Bemt, Vos, den Broeder, Blom, Thurlings, Bartelds, Nurmohamed, Barrera, Tak, Wolbink; Nijmengen, Netherlands.

Jon Giles

Objectives

Anti-infliximab antibodies can reduce the efficacy of infliximab.  Treatment with an agent that may serve to reduce the production of these antibodies, such as the anti-CD20 monoclonal antibody rituximab, may be useful in regaining the efficacy of infliximab in RA patients who produce anti-infliximab antibodies.

Method

RA patients with anti-infliximab antibodies who were to receive therapy with either rituximab or adalimumab were followed prospectively.  Differences in anti-infliximab antibody levels were compared at baseline and after 16 and 24 weeks of therapy.  Patients received standard dosing for both medications (rituximab 1000 mg x 2; adalimumab 40 mg every other week) as part of clinical care.

Results

There were 17 rituximab and 15 adalimumab treated patients studied.  Mean age was 56 years in rituximab patients compared to 53 years in adalimumab patients.  Mean disease duration was 16 years in both groups.  Baseline DAS28 was slightly higher in rituximab treated patients vs. adalimumab treated patients (mean 6.0 vs. 5.0, respectively).  Patients in the rituximab group had a longer time from last infliximab infusion compared to adalimumab treated patients (mean 25 vs. 6 months, respectively).

Baseline anti-infliximab antibody levels were higher in the group that subsequently received adalimumab compared to those who received rituximab (100 u/ml vs. 29 u/ml, respectively).  Antibody levels decreased at 24 weeks by 20% in rituximab treated patients compared to 36% in adalimumab treated patients (difference not statistically significant).  One patient seroconverted to negative for anti-infliximab antibodies (a patient in the adalimumab group).  There was no difference in groups in multivariable analyses adjusted for baseline antibody levels or time from last infliximab infusion.

Conclusions

Rituximab did not alter anti-infliximab antibody status in RA patients with anti-infliximab antibodies prior to rituximab treatment.

Editorial Comment

This is a very creative proof of concept project.  Even so, the supposition that a single treatment course of rituximab could abrogate an established antibody response given that rituximab does not affect plasma cells responsible for manufacturing antibodies increases the pre-test probability of failure for the study.  However, the concept may not be entirely a loss, as repeated courses of rituximab or treatment before the development of anti-infliximab antibodies could affect antibody levels.  Unfortunately, these are less practical alternatives than the design reported here.  Importantly, treatment allocation was not randomly assigned, thus confounding by indication could diminish any true differences between the groups, if they existed.  However, this possibility is unlikely.