OBJECTIVES: Model conceptualisation is iterative, involving a substantial number of choices. Our research: (i) demonstrates the importance of model conceptualisation in the context of a chronic and progressive disease, such as AS and nr-AxSpA; and (ii) highlights practical issues that arise when developing a model. METHODS: Current published models in AS and nr-AxSpA employ changes in disease activity (BASDAI) and/or function (BASFI) to quantitatively model the impact of anti-TNFs versus best supportive care. Longer-term BASDAI is assumed constant, thus disease progression is modelled entirely via a linear change in BASFI, based on external natural history estimates. This raises conceptual concerns, since this type of structure appears driven by data availability rather than based on a clear underlying clinical process. It also raises challenges in modelling subgroups or different indications, if different clinical processes apply. Our model used a different conceptual structure, to explicitly reflect the progressive nature of AS and nr-AxSpA. We modelled the potential impact of anti-TNFs on the different processes which independently relate to BASFI over time. We considered the effects on BASFI due to reductions in disease activity (i.e. symptomatic improvements) and due to effect on the progression of radiographic disease (i.e. disease modification properties). The latter is particularly important since it is a strong independent predictor of functional impairment, not formally considered within existing studies. RESULTS: Our approach provided similar results to existing models. However, we adopted a different conceptual structure, clearly linking BASFI progression to evidence from radiographic assessments, thus explicitly modelled separate BASFI changes across the separate indications. CONCLUSIONS: This case study illustrates the different approaches in model conceptualisation (i) based on the clinical problem being considered versus (ii) being driven by data availability. Our study demonstrates the importance of ensuring a coherent and explicit clinical basis for modelling a chronic and progressive disease.