ABSTRACT: INTRODUCTION: The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients. METHODS: In 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level and total dose of Nonsteroidal anti-inflammatory drug (NSAID) was dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether BMI was predictive of response to IFX therapy according to these definitions was assessed with logistic regression. RESULTS: Multivariate analysis found a higher BMI was associated with a lower response for BASDAI50 (P=0.0003, OR 0.87 95%CI0.81-0.94VAS50 (P<0.0001, OR 0.87 95%CI[0.80-0.93]), CRP50 (P=0.0279, OR 0.93 95%CI0.88-0.99) and NSAID50 (P=0.0077, OR 0.91 95%CI0.85-0.97criteria. According to the 3 WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9% and 26.5%, P<0.0001), VAS50 (72.6%, 40.4% and 16.7%, P<0.0001), CRP50 (87.5%, 65.7% and 38.5%, P=0.0001) and NSAID50 (63.2%, 51.5% and 34.6%, P=0.06). CONCLUSIONS: This study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response.