Several findings provide support for the window of opportunity hypothesis: an increase in the risk of persistent disease after several months of arthritis symptoms [15, 16]; differences in immunological abnormalities in very early compared with established disease [17, 18]; and the ability of early treatment with a tumour necrosis factor (TNF) inhibitor plus methotrexate (MTX) to allow some patients with RA to achieve a drug-free remission [19, 20]. Here, TNF is linked to arthritic joint disease.