Abstract
Objectives: To assess the incidence of secondary hypogammaglobulinemia in patients with rheumatoid arthritis (RA) following multiple cycles of rituximab (RTX) related to two different therapy regimens. Methods: 73 patients with RA were retreated using 6 months-fixed strategy and 63 patients using a non-fixed regimen. All received ≥ 2 courses of RTX. Data on serum immunoglobulins (Ig), serious infections and DAS28 were collected, with maximum follow-up being 24 months for the 6 months fixed group and 156 months for the non-fixed group). Statistics for non-parametric analysis were applied. Results: The percentages of patients developing low IgG or IgM did not differ between groups after the 3rd cycle, but those with non-fixed retreatment tended to be higher. After 4 cycles, median IgM levels were significantly lower in both groups compared with pretreatment (p<0.05). Only patients in the fixed retreatment group receiving 4 cycles of treatment showed a significant drop in median IgG level (p<0.05). IgA levels remained within the normal range. Withdrawals due to infections per 100 patient years (py)s in patients with low IgG were higher after 3 Cycles in patients within the fixed retreatment group (4.60/100py vs 1.36/100py, CI: 0.59, 6.23). DAS28 did not differ between cohorts after multiple cycles. Conclusions: Although the percentage of RA patients developing low IgG tended to be higher in the nonfixed group, median IgG level was significantly lower after 4 Cycles of RTX in the fixed regimen group. The fixed retreatment group also had more patients discontinuing rituximab over a shorter period of time (24 months compared with 156 months), with no significant differences in median DAS28 after multiple Cycles. If multiple cycles of RTX are to be instituted, non-fixed regime may allow the opportunity to control the disease with a lower incidence of withdrawal due to low Igs and infections.
Highlights
In patients with rheumatoid arthritis (RA), the rationale of B cell depletion therapy (BCDT) based on Rituximab (RTX) was to eliminate autoreactive B cell clones, as precursors of autoantibody secreting cells, while minimizing the period of impact on normal B cells and protective antibody production [1]
Reconstitution of memory B cells (CD27+) following RTX in RA is often slow [7] and falls in total immunoglobulin levels following single cycles of BCDT based on RTX are modest, there is evidence for progressive decrease with repeated cycles [3,8,9]
We suggest that patients were comparable between centers in relation to the objectives analyzed here, i.e. immunoglobulin dynamics and infections
Summary
In patients with RA, the rationale of B cell depletion therapy (BCDT) based on Rituximab (RTX) was to eliminate autoreactive B cell clones, as precursors of autoantibody secreting cells, while minimizing the period of impact on normal B cells and protective antibody production [1]. Reconstitution of memory B cells (CD27+) following RTX in RA is often slow [7] and falls in total immunoglobulin levels following single cycles of BCDT based on RTX are modest, there is evidence for progressive decrease with repeated cycles [3,8,9]. Pooled analysis of safety data from the global clinical trial program from Roche and Genentech, showed that the proportion of patients with low IgM at 6 months post-RTX increased with each additional course from 10% of patients after 1st cycle to up to 40% following 5 cycles. The proportion of patients with low IgG by course remained relatively stable, from 3%–6% [8] in clinical practice a progressive fall has been reported [9]. The practical application of results obtained in clinical trials, where patients are by definition selected for admission, to the treatment of consecutive patients attending clinics can be confusing
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