OBJECTIVES: To establish the total direct medical cost of patients in second-line TNF a therapy from the French heath care system perspective. METHODS: A multicentre observational study was conducted, recruiting patients treated since at least four months by a second TNF a therapy. The sample represented was assessed through the comparison of the regional allocation of inclusions to the regional allocation of TNF a prescriptions issued from a national panel. Inpatient and outpatient consumptions were collected retrospectively, for the preceding four months. Respect of clinical practice recommendations was assessed through the analysis of administration frequencies and posologies. RESULTS:  Fifty-nine hospital centres participated in the study, including 277 patients. The sample could be considered as representative as the correlation between the regional activity in terms of TNF a prescriptions and the number of included patients per region was high (r = 0.88). The resulting total annual direct medical cost equalled €16,000 per patient. Respectively 43, 132, and 102 patients were included in the INF, ETA and ADA groups. Two patients treated by INF received more than the expected number of administrations, whereas 8 others had a higher dosage than that recommended. Respectively 11.4% and 24.5% of patients treated by ETA and ADA also received more administrations than expected during the 4 months of treatment. CONCLUSIONS: This representative study stated that hospitalisation costs represented 92% of the total direct medical costs of patients treated by a second-line TNF a therapy, reaching €16,000 per patient and per year. In the absence of a specific market authorisation in the indication, TNF a therapies are prescribed, but the clinical practice recommendations are not always respected.