Background Secondary loss of efficacy to individual treatments in patients with rheumatoid arthritis (RA) is well described. It is not clear whether pharmacokinetic or pharmacodynamic changes have taken place or whether the pathogenic process has changed and is no longer controlled by the previous therapeutic approach. However, secondary loss of efficacy of Rituximab (RTX) is not often reported.
Objectives To analyse whether there is a significant loss of efficacy to RTX and factors related to it.
Methods Retrospective analysis of the RA cohort treated with B cell depletion therapy based on RTX at University College London Hospital, selecting patients with an initial response to their first RTX cycle, but loss of efficacy after subsequent cycles.
Results We reviewed 176 RA patients on RTX therapy, who had received at least 2 cycles of RTX (up to 10 cycles), followed for at least 1 year (up to 13 years). We identified 10 patients (5.7%), one man and nine women, who had had an initial response to RTX on their first cycle but seemed to have lost efficacy in subsequent cycles, and analysed possible factors contributing to it. A response was based on clinical parameters, decrease of CRP and ESR and DAS28 score. All 10 patients were rheumatoid factor (RF) and anti-CCP positive at baseline, had a mean number of cycles of 3.4 (range 2-7 cycles). All had been treated previously with different DMARDs and, 8 of them with at least one TNF inhibitor (mean 1.9). Two patients had not been eligible for anti TNF therapy because of a previous history of solid cancer. Levels of CD19 cells, RF, CRP and ESR were analysed precycle, at minimum levels following treatment and at relapse.
Based on our findings, we divided the patients into two groups, distinguishing patients with a gradual loss of efficacy or a shorter time of response and patients who did not show any clinical or serological response after retreatment with RTX.
The first group (5 patients) had an initial good response for a mean time of 10.8 months (range 6-36 months) and they had a less or shorter response time in their last cycle (range 3- 7 cycles) down to 3.9 months (range 2-5 months). No cases were associated with insufficient depletion. Three patients had decreased their prednisolone dose before the last cycle of RTX received, and the other two patients had not changed their concomitant therapy.
The second group (5 patients) had a good response to their first cycle for at least 4 months (mean 6.9 months, range 4-12 months), but no response to the second one. Initially, relapse of the disease usually coincided with repopulation of B cells in peripheral blood. Two patients had inadequate B cell depletion after the second cycle. Two patients had had changes in their treatment before the last cycle.
Conclusions Secondary loss of efficacy of RTX is infrequent. Different reasons may explain the lack or loss of response after retreatment with RTX. Changes in concomitant therapy or inadequate depletion should be ruled out. Treatment adjustments may be helpful and patients with inadequate depletion may still be eligible for B cell targeting therapies in the future.
Disclosure of Interest C. Marin- Huertas Grant/Research support from: The Spanish Society of Rheumatology, E. Becerra: None Declared, I. de la Torre: None Declared, G. Cambridge: None Declared, J. Edwards: None Declared, M. Leandro: None Declared
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