Tocilizumab reduces neutrophil count in rheumatoid arthritis patients

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Tocilizumab reduces neutrophil count in rheumatoid arthritis patients

Neutrophils are an integral part of  the process of inflammation in rheumaoid arthritis (RA). They regulate the function of other immune cells, the upregulation of expression of plasma membrane receptors (like MHC class II antigens), cell–cell interactions (like NK cell activation) and the free the proteases that activate or deactivate cytokines and chemokines. Tocilizumab (TCZ) is a recombinant, humanized, anti-human intra lukin 6R (IL-6R) mAb that attaches to soluble and membrane-bound IL-6R-α and impedes IL-6 signalling pathways.

Moots RJ et al  conducted a study to find out the changes in neutrophil count and the development of infection in RA patients treated with the IL-6 receptor-α inhibitor TCZ. To serve the purposes of this study, data was pooled from patients who acquired i.v. TCZ (4 mg/kg + MTX, 8 mg/kg ± DMARDs, 10 mg/kg) or placebo + DMARDs in phase 3/4 clinical trials, long-term extensions or a pharmacology study. As per the Common Toxicity Criteria for adverse events grades, the neutrophil counts were assesssed routinely. The dosage of TCZ was adjusted as and when required. Covariates linked with the decreased neutrophil count were assessed with multivariate regression analysis. The infection rates within 30 days of neutrophil count changes were determined per 100 patient-years of TCZ exposure.

More TCZ-treated than placebo-treated patients had grade 1/2 or 3/4 neutrophil counts (TCZ: 28.2%/3.1%; placebo: 8.9%/0.2%) in placebo-controlled trials. Overall, 4171 patients provided 16204.8 patient-years of TCZ exposure in the placebo-controlled trials + long-term extensions. Through week 6 from baseline [mean (SD) change, -2.17 (2.16) × 109/l), the neutrophil counts declined and remained stable afterwards. The rates (95% CI) of serious infections within 30 days of normal [4.66 (4.31, 5.03)], grade 1/2 [2.48 (1.79, 3.34)] and 3/4 [2.77 (0.34, 10.01)] neutrophil counts were alike. Baseline neutrophil count <2 × 109/l and female gender were connected with grade 3/4 neutrophil counts [odds ratio (OR) (95% CI): 19.02 (6.76, 53.52), 2.55 (1.40, 4.66)]. The patients who ceased TCZ in response to decreased neutrophil count resumed to normal levels faster than patients who reduced or sustained their dose.

It was thus culminated that the reduction in neutrophil counts in patients taking TCZ do not appear to be linked with serious infections and are normalized by current risk mitigation guidelines.

Source:

Rheumatology (Oxford)

Link to the source:

https://www.ncbi.nlm.nih.gov/pubmed/28013198

Original title of article:

Effect of tocilizumab on neutrophils in adult patients with rheumatoid arthritis: pooled analysis of data from phase 3 and 4 clinical trials.

Authors:

 Moots RJ et al.

Rheumatology (Oxford)
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