Leijer, J.H. de (2021) REDO trial: Rituximab dose-dependent infection risk in rheumatoid arthritis not mediated through immunoglobulins, neutrophils or B-cells. thesis, Medicine.
Full text available on request.Abstract
Background Rituximab (RTX) is a safe and effective treatment for rheumatoid arthritis (RA). RTX depletes B-cells, which can lead to decreased levels of protective immunoglobulins after repeated courses. Clinical trials find RTX not to be associated with additional infection risk in RA, whereas cohort studies generally report higher infection rates and identify risk factors for infection such as hypogammaglobulinemia (HGG), low immunoglobulin levels, and neutropenia. The REDO trial compared ultra-low doses of RTX (500mg and 200mg) to standard dose (1000mg) and found significant reductions in infection rate. This study is a further exploration of this dose-dependent infection risk including a mediation analysis. Methods Potential mediators and suppressors were selected and immunoglobulin levels were measured post-hoc. A step-wise analysis was performed to investigate to what extent their RTX dose-induced changes contributed to the observed differences in infection risk. Indirect effects were computed using the traditional (Poisson) regression approach or the causal interference framework and corrected for confounders. Infection incidence rates over time were compared between RTX dosing groups using linear regression models. Results 131 REDO participants were included, of which 27 in the 1000mg group, 52 in the 500mg group, and 52 in the 200mg group. No mediation of the REDO dose-dependent infection risk was seen for B-cell counts, immunoglobulin G, M, or A levels, HGG, and neutrophil counts. Similarly, oral corticosteroid use, corticosteroid injections, and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) did not suppress this effect. Significant differences between infection incidence rates over time were observed between RTX dosing groups, in which a higher dose of RTX showed a larger decline in infection trend over time (p=0.037). Conclusions This secondary analysis of the REDO trial could not provide mediating pathways for a dose-dependent infection risk.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Broeder, Dr. A. den and Opdam, Drs. M. and Vonkeman, Dr. H. |
| Faculty: | Medical Sciences |
| Date Deposited: | 24 Dec 2021 11:03 |
| Last Modified: | 24 Dec 2021 11:03 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2914 |
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