The lack of detrimental toxicity of the C5aR1 antagonist PMX53 and CCX168 in human clinical trials of refractory rheumatoid arthritis [93] and ANCA-associated vasculitis [94], and the clinical experience with FDA approved Eculizumab, an anti C5 monoclonal antibody that prevents the cleavage of C5 and thus the generation of C5a [95], suggests that suppression of C5a/C5aR1 signaling may not be harmful for extended clinical use in adults. This evidence concerns the gene C5 and rheumatoid arthritis.