Objective To explore the effect of comedication with conventional synthetic disease modifying antirheumatic drugs (csDMARDs) on drug retention and clinical effectiveness of tumour necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). Methods Inclusion of all patients starting treatment with a TNFi in a large prospective axSpA cohort (SCQM-axSpA). Crude drug retention was analyzed using the Kaplan Meier method and in adjusted analyses we used Cox proportional hazard regression to model TNFi discontinuation. We evaluated multiple disease activity measures and validated clinical response criteria over time. Results A total of 2765 TNFi treatment courses were included from 1914 axSpA patients, with 20.4% in combination with a csDMARD. In unadjusted analyses, the monotherapy group had significantly shorter median TNFi retention time (32.7 months), compared to the co-therapy group (39.1 months) (p= 0.04). In multivariate adjusted analyses, the monotherapy group had significantly lower TNFi retention, with a hazard ratio (HR) of 1.17 (95%CI: 1.01;1.35). This effect was even larger when considering only Infliximab treated patients, with a HR for monotherapy of 1.36 (95%CI: 1.06;1.74). Clinical response rates were almost identical at 1 year with a change in the Bath Ankylosing Spondylitis Disease Activity Index of -2.02 and -2.00 (p=0.83) and a change in the Ankylosing Spondylitis Disease Activity Score using CRP of -1.14 and -1.12 (p=0.45) in the monotherapy and co-therapy groups respectively. Conclusion We demonstrate an association between the combination of a TNFi with csDMARDs and improved drug retention in axSpA patients, particularly in the subgroup of patients with Infliximab. This article is protected by copyright. All rights reserved.