Background/Purpose: CD4+ T-cell depletion after a first cycle of rituximab (RTX) in patients with rheumatoid arthritis (RA) was previously reported by our group (Mélet J et al. Arthritis Rheum 2013). This effect was not observed in non-responders. The aim of the study was to describe CD4+ T-cell changes over multiple, repeated cycles of RTX (two infusions of 1000 mg each, 2 weeks apart) and their potential relationship with disease activity.

Methods: Patients who started RTX for treatment of RA in our centre between July 2007 and July 2013 were included and studied retrospectively until November 2014. Disease activity was assessed by disease activity score on 28 joints (DAS28) and peripheral blood CD4+ T-cell counts were measured by flow cytometry. In each cycle, pre-treatment, post-treatment and re-treatment CD4+ T-cell counts were compared using Wilcoxon’s matched-pairs signed rank test.

Results: In each cycle, the mean CD4+ T-cell count was systematically above the normal range prior to the first and second infusions. The improved clinical response observed with the repeated RTX treatment was associated with normalisation of the mean CD4+ T-cell count in each cycle, this effect being slightly additive. Post-RTX CD4+ T-cell counts were sometimes below 300/mm³. B-cell counts usually remained low when patients were re-treated. Conversely, RTX-induced CD4+ T-cell depletion was temporary and was followed by an almost complete recovery of the pre-treatment count. Additionally, all of the non-responders to cycle 1 demonstrated only a small decrease or even an increase in CD4+ T-cells in this first cycle; of the non-responders to cycle 1 who were subsequently re-treated, those who had high depletion (i.e.>33%) in the second cycle were more likely to be responders than others (11 of 11 versus 11 of 21). Interestingly, 80 % of these patients became responders and had greater CD4+ depletion in cycle 2 than in cycle 1.

Conclusion: Repeated post-treatment CD4+ T-cell depletion occur over successive cycles of RTX in RA patients. These results suggest that CD4+ T-cell variations induced by RTX are more closely related to changes in disease activity than B-cell variations. Monitoring circulating CD4+ T-cells might be helpful for clinicians when assessing disease activity and also for consequent evaluation of treatment efficacy or for the determination of re-treatment intervals in RTX-treated RA patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/repeated-cd4-t-cell-depletion-in-patients-with-rheumatoid-arthritis-over-multiple-cycles-of-rituximab-treatment/