The present study investigated the ability of 18F-FDG PET to track disease activity, both cross-sectionally and longitudinally, in AS and PsA patients who were candidates for initiation of biologic therapy. We found that 18F-FDG uptake in clinically involved joints/entheses was strongly correlated with pre-treatment disease activity in patients with AS. This result was supported by our longitudinal analysis, in which we confirmed that more pronounced decreases in 18F-FDG uptake were significantly associated with better responses to biologic treatment, both in AS and PsA participants. Together, our findings indicate that 18F-FDG PET may be a useful tool for objective monitorisation of disease activity and assessment of treatment response in AS and PsA patients undergoing therapy with biologics.
A number of prior cross-sectional studies investigated the ability of 18F-FDG PET for the detection of lesions in patients with AS (16–18, 25). However, the potential of 18F-FDG PET as an objective marker of disease activity in AS remains largely unexplored, with only two case reports (n ≤ 3 participants, (30, 31)) suggesting potential of 18F-FDG PET to monitor treatment effects in patients with AS. Here, we provide the largest analysis to date supporting this notion. By performing quantification of 18F-FDG uptake, we first demonstrated that clinically involved joints/entheses showed a statistically significant increase of 30% in 18F-FDG uptake compared to uninvolved regions. Although this result aligns well with findings from previous reports (16–18), a previous study showed no elevations in 18F-FDG uptake in 10 out of 12 AS patients (25). These conflicting results are, however, likely explained by differences in the characteristics of the AS population studied in (25), which includes patients with low disease activity (n = 5) and an overall milder inflammatory state (only 3 of these patients showed bone edema on MRI). Despite this controversy, our study provides novel evidence supporting the ability of 18F-FDG PET to capture disease-related inflammatory processes. We found that pre-treatment 18F-FDG uptake in the clinically involved joints/entheses, as measured with the composite measure gSUVmax, was strongly correlated with pre-treatment disease activity, as reflected by the ASDAS score. Furthermore, we confirmed this cross-sectional result in the longitudinal analysis, which showed that larger clinical benefits were accompanied by larger decreases in 18F-FDG uptake of the clinically involved joints/entheses. Our results suggest that 18F-FDG PET may be a useful marker of disease activity in AS patients with clinically active disease. 18F-FDG PET may also have a relevant application for tracking treatment effects in therapeutic trials or clinical settings.
The pattern of findings in our PsA cohort is less clear, though still consistent with our findings in AS patients. We found that clinically involved joints/entheses displayed ~ 25% higher 18F-FDG uptake compared to unaffected regions; however, we did not find a statistically significant association between pre-treatment 18F-FDG uptake and disease activity. This result may be explained by the lower sample size of the PsA group (n = 8) together with the relatively homogeneous distribution of DAPSA scores (range: [18–34]), which may result in a limitation of the power to detect a statistical association. Yet, in line with our findings in AS patients, we did find a statistically significant association between stronger clinical improvements and longitudinal decreases in 18F-FDG uptake in the affected regions. Together, these findings extend previous results indicating that 18F-FDG PET can capture inflammatory processes in PsA (22), and support the notion that this imaging modality may also represent a useful marker of disease activity and treatment effectiveness. However, additional studies with larger sample sizes and wider range of baseline disease activity are needed to confirm these results.
Interestingly, we did not find a statistically significant association between pre-treatment 18F-FDG uptake and clinical response to biological treatment at follow-up. This result resonates with findings from previous studies using 18F-NaF PET, in which pre-treatment uptake was not predictive of clinical response to TNFα antagonist therapy (26). These results suggest that the factors that influence the likelihood of clinical response are not fully captured by PET imaging with 18F-FDG or 18F-NaF. Nevertheless, it is still possible that pre-treatment 18F-FDG uptake could be predictive of clinical response in different patient populations, in particular in those at a more severe disease stage. Given that 18F-FDG uptake correlates well with disease activity, it is likely that higher pre-treatment 18F-FDG uptake may be associated with better clinical response, as patients with high baseline disease activity tend to respond better to biological treatment (32). Further studies are warranted to clarify the power of 18F-FDG PET to predict clinical response in AS and PsA patients undergoing therapy with biologics.
The present study had a number of limitations. First, although relatively large for a PET imaging study on AS and PsA patients, the sample size of our study was modest, particularly for the longitudinal analysis. Second, our inclusion criteria led to relatively homogenous clinical characteristics for our study participants. This may have limited our statistical power to detect associations between 18F-FDG PET and disease severity scores. The performance of 18F-FDG PET may also vary for more diverse patient populations. Third, study participants underwent different treatment regimes, which might have influenced our longitudinal findings. Fourth, due to low the sample size in, we were underpowered to analyse how 18F-FDG uptake in specific joints/entheses influenced clinical outcomes.
In summary, we provided first-time evidence suggesting that 18F-FDG PET is an accurate marker of disease activity in patients with AS and PsA. Our findings suggest that 18F-FDG PET may be a useful surrogate marker of treatment effectiveness in therapeutic trials for AS or PsA, and may provide valuable information to clinicians evaluating clinical response to biologic treatments.