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 RA B-Cell DepletionAbstract 725: Long-Term Efficacy and Safety of a Repeat Treatment Course of Rituximab in Rheumatoid Arthritis Patients with an Inadequate Response to One or More TNF InhibitorsRituximab, a monoclonal antibody directed against B-cells, has been shown to be highly effective in treating the signs and symptoms of RA and in delaying radiographic progression. However, the bulk of this data is from subjects who have received only one infusion course of the drug. Questions remain regarding the sustainability of the clinical response on repeated infusion courses and whether safety concerns accumulate over time. Here, Keystone et al. report safety and efficacy results of subjects who have received two infusion courses of rituximab in clinical trials enrolling subjects with inadequate responses to TNF inhibitors. Methods Data derive from clinical trials of rituximab in which subjects with inadequate responses to one or more TNF inhibitors were enrolled (n=570). Of these, 155 had received a second (retreatment) course of rituximab and had completed follow-up data to 24 weeks. Subjects were all receiving background methotrexate. Clinical responses at 24 weeks after each course of rituximab were calculated in relation to the subjects’ original baseline and in relation to their new baseline at the time of retreatment. Results Of the 155 subjects, 80% were female with a mean age of 52 years at enrollment. Eighty percent were seropositive for rheumatoid factor. Mean disease duration at enrollment was 11.6 years. Disease activity at baseline was high, with a mean of 23 swollen and 34 tender joints, mean DAS28 of 6.9, and mean CRP of 3.6 mg/dL. The mean number of prior failed TNF inhibitors was 1.5.
Clinical response was similar, if not slightly improved, after 24 weeks on retreatment to the initial rituximab treatment course. DAS28 and EULAR responses were comparable to ACR responses. Adverse and serious adverse events were not increased after the second retreatment course. Conclusions Clinical responses across groups do not appear to diminish after the first retreatment course of rituximab in patients with a prior inadequate response to TNF inhibitors. At the same time, safety issues do not appear to be increased. Editorial Comment These results are similar to those reported at EULAR this year (link to OP0017). The difference is that these results are in subjects with prior exposure to biologics, a group in which safety issues (particularly infections) might be increased. Although the results on the sustainability of response over repeated courses are encouraging, longer term follow-up is required for confirmation. Since most patients will require retreatment every 6 to 12 months, it is possible that a decline in treatment response or an increase in safety issues will occur after multiple infusions. These results compare proportional responses by group. A slightly more informative way to look at the differences in responses between treatments would be to compare the range of individual changes in responses. This would reveal whether the apparent stability in proportional response averaged over the entire group is due to subjects maintaining their original responses, or whether the observed stability in group response is made up of subjects who did better on the second treatment course mixed in with a comparable number of patients who did worse.
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