The refractory state model, which contained the largest number of unique genes, included several linked to the fibroid pathotype such as TNFRSF11B, which encodes the osteoclast negative regulator osteoprotegerin and the chondrocyte adhesion mediator CHAD (chondroadherin), but also the citrullination enzyme PAD4 encoding gene PADI419, consistent with a role of persistent tissue destruction and remodeling in the refractory RA state. Here, CHAD is linked to rheumatoid arthritis.