Current guidelines on the use of anti-tumour necrosis factor alpha (anti-TNF-α) therapies in rheumatoid arthritis (RA) recommend a 3-month trial of the drug before a clinical assessment of treatment efficacy can be made. The serum level of the type II collagen propeptide CPII correlates with type II collagen synthesis, and is elevated in RA. The collagen cleavage neo-epitope C2C is specific for the destruction of type II collagen by the collagenases MMP-1, MMP-8 and MMP-13. Previously we have shown that the ratio of C2C/CPII is increased in osteoarthritis and correlates with cartilage destruction. The current pilot study assessed the utility of serum measurement of C2C and CPII in predicting early response to treatment with anti-TNF-α therapy in a group of 20 RA patients.