The disconnect between objective inflammatory response and PROs in AxSpA Save

The assessment of disease activity in AxSpA involves the use of objective inflammatory response (OIR) and patient reported outcomes (PROs). In clinics, a combination of OIR and PROs are used to measure disease activity and response to treatment. OIR includes measurements such as CRP and MRI inflammatory lesions. PROs include measurements for pain, fatigue and quality of life (QOL). PROs are often captured using composite scores such as the BASDAI, BASFI and ASDAS. 

The drive is towards a treatment to target (T2T) strategy where an outcome is measured regularly and interventions put into place to achieve an outcome below or above a set target.

OIRs are used as they are accepted as more precise in measuring disease activity. PROs may be influenced by other factors such as pain or fatigue which may affect its score. Physicians may be more focused on OIRs to determine the management including escalation to biologic therapies. A raised CRP and positive MRI are strong predictors of good response to biologic therapies. On the other hand, patients may place a higher weighting on their QOL as this has an impact on their independence, working ability and wellbeing. 

This potential disconnect between OIR and PROs is discussed in Abstract 0543 at ACR22. This is a post hoc analysis of 136 patients with AxSpA receiving Certolizumab (CZP) in the RAPID-axSPA trial. The OIRs included CRP and MRI scores (CRP, ASspiMRI Berlin score and MRI SPARCC SIJ score). PROs used included BASDAI and ASDAS, acknowledging that ASDAS does contain the CRP. Following treatment with CZP, CRP, ASspiMRI Berlin score, and MRI SPARCC SIJ score were reduced by >50%, in the majority of pts. In some patients there was >75% improvement in these OIRs. However, only a minority of patients showed a >50% reduction in the PROs (BASDAI and ASDAS). These results were also observed at the individual patient level where the >50% improvements in MRI/CRP inflammatory measures did not translate into similar improvements in PROs for the majority of patients.

This post hoc analysis revealed a potential disconnect between OIRs, as measured by MRI and CRP, and PROs. In the majority of patients, CZP treatment resulted in a reduction of OIRs irrespective of improvements in PROs. The clinical response as measured by PROs may be affected by non-inflammatory factors that drive the scores. While symptoms such as pain, fatigue, mood and independence are linked in part to inflammation, there is also a non-inflammatory component to this. Thus, improvement in CRP or MRI changes may not necessarily correlate with the clinical outcomes measured by PROs.

The use of PROs as clinical trial endpoints may therefore underestimate anti-inflammatory treatment effects. Going forward, there will be a need to have parallel outcome measures to capture response to treatment in a holistic way. This will lead to a more accurate assessment of disease activity in AxSpA.