Background: The aim of our study was to investigate the influence of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and body mass index (BMI) on circulating drug levels and clinical response to tumour necrosis factor inhibitor (TNFi) therapy in axial spondyloarthritis (axSpA) patients. Methods: Prospective observational study during 1 year with 2 cohorts (Madrid and Amsterdam) including 180 axSpA patients treated with standard doses of infliximab or adalimumab. Patients were stratified by BMI, being 78 (43%) normal weight (18.5-24.9 kg/m 2 ) and 102 (57%) overweight/obese (≥ 25.0 kg/m 2 ). After the first year of treatment, TNFi trough levels were measured by capture ELISA. Clinical response to TNFi was defined as FOR VERIFICATION BASDAI ≥ 2 and clinical remission as BASDAI < 2 and CRP ≤ 5 mg/L. Logistic regression models were employed to analyse the association between concomitant csDMARDs and BMI with drug levels and clinical response. Results: Seventy-nine patients (44%) received concomitant csDMARDs. The administration of concomitant csDMARDs (OR 3.82; 95% CI 1.06-13.84) and being normal weight (OR 18.38; 95% CI 2.24-150.63) were independently associated with serum TNFi drug persistence. Additionally, the use of concomitant csDMARDs contributed positively to achieve clinical response (OR 7.86; 95% CI 2.39-25.78) and remission (OR 4.84; 95% CI 1.09-21.36) in overweight/obese patients, but no association was found for normal-weight patients (OR 1.10; 0.33-3.58). Conclusions: The use of concomitant csDMARDs with TNFi may increase the probability of achieving clinical response in overweight/obese axSpA patients. Further research studies including larger cohorts of patients need to be done to confirm it.