Background: The aim of this study was to evaluate the relevance of drug and anti-drug antibody detection in the clinical management of patients with rheumatoid arthritis (RA) and spondyloarthropaties (SpA) in treatment with anti-tumor necrosis factor alpha (TNFα) biologics. Methods and results:The study included 192 adult consecutive patients treated for at least 6 months with adalimumab (ADA) or etanercept (ETN) or infliximab (IFX); patients underwent clinical observations in the Rheumatologic Unit of 5 Hospitals in Tuscany. Their demographic and clinical characteristics to calculate DAS28 and BASDAI scores were collected. Drug levels and anti-drug antibodies (anti-drug Ab) were evaluated immediately before drug injection or infusion. A total of 192 patients were studied: 62 receiving IFX, 64 ADA, and 66 ETN with a mean age of 57 years (range 18-86 years); the study group was composed of 51% women. Forty percent of the patients were affected by RA, 60% by SpA. Altogether, 81% of patients demonstrated therapeutic drug levels. Anti-drug Ab were found in 19% of patients taking IFX, 10% taking ETN and 5% taking ADA. No significant correlation was found between anti-drug Ab presence and low drug levels, between anti-drug Ab and high DAS28 and BASDAI scores, as well as between low drug levels and high DAS28 and BASDAI scores. Conclusions: Low drug levels were found in 19% of the rheumatic patients and there were not correlations with presence of anti-drug Ab or patient's clinical status.