Validation of assessment methods for the apparent diffusion coefficient in a clinical trial of axial spondyloarthritis patients treated with golimumab

Purpose To compare three region-of-interest (ROI) settings in the assessment of ADC in a clinical trial, and to evaluate the effectiveness of ADC in assessing therapy-induced changes and predicting clinical outcomes. Methods In a 52-week clinical trial involving patients with axial spondyloarthritis, mean sacroiliac joint (SIJ) ADC measurements using structured, lesion-based, and index-lesion ROI-settings were assessed at baseline and weeks 4, 16, and 52. Variation among the three ROI-settings, correlations with Spondyloarthritis Research Consortium of Canada (SPARCC)-bone marrow edema (BME) SIJ inflammation indices, standardized response means (SRMs), and effectiveness in predicting clinical outcomes were analyzed. Results Forty of the 53 patients had at least one assessable SIJ lesion on ADC at baseline. The mean of the structured ROI ADC (ADCstruc) was 230 μmm2/s (standard deviation [SD] = 120). This was significantly lower (p < 0.01) than the means of the lesion-based ROI ADC (ADClesion = 420 μmm2/s, SD = 210) and index-lesion ROI ADC (ADCindex = 471 μmm2/s, SD = 278), which did not differ. ADC correlated with SPARCC-BME scores at baseline (p < 0.01) as did changes over time in ADC- and SPARCC-BME (p<0.05). At all follow-up time points, responsiveness was high for ADClesion (SRM > 0.92) and ADCindex (SRM > 0.87) while moderate for ADCstruc (SRM:0.54-0.67). Baseline ADC and changes in ADC did not predict clinical outcomes. Conclusions Lesion-based and index-lesion ROI ADC could both be used to evaluate the effectiveness of tumor necrosis factor inhibitor therapy. None of the methods could predict clinical outcomes.