Background/Purpose:

Axial Spondyloarthritis (AxSpA) encompasses both non-radiographic (nr-AxSpA) as well as radiographic ankylosing spondylitis (AS) which displays structural changes at the sacro-iliac joint (SIJ).  Phase 2 and 3 clinical trials are currently ongoing requiring imaging-based eligibility of subjects based on the protocol specific target population for the type of disease (nr-AxSpA vs. AS). The currently accepted modified New York (mNY) criterion includes a radiographic assessment of the SI joint. In clinical trials the subjects deemed locally to be good candidates either for an AS or an nr-AxSpA trial have an SIJ X-ray examination read centrally to determine eligibility (mNY+ for AS and mNY- for nrAxSpA). For nr-AxSpA trials, an MRI examination of the SIJ is also obtained to confirm inflammation per ASAS/OMERACT guidelines; mNY- with positive MRI (MRI+) subjects are deemed eligible for these trials. Therefore, for prospective trial design it is important to understand the percentages of subjects likely to be deemed eligible by central imaging review and how many subjects will screen-fail for either AS (mNY+) or nr-AxSpA (mNY-).

Methods:

 A total of 4782 subjects from seven trials were assessed for mNY +/- and/or MRI+/-. 2 studies (n=1419) had both an AS or and nr-AxSpA cohort and subjects were recruited according to mNY+ (for AS cohort) or mNY-/MRI+ (for nr-AxSpA cohort). 3 studies (n=821) had mNY+ as the imaging inclusion criteria and 2 studies (n=2496) had mNY- / MRI+ as the imaging inclusion criteria. The read model was either a single or double read. Percentage of subjects deemed either eligible for AS (mNY+) or nr-AxSpA (mNY-/MRI+) was calculated. We also calculated the percentage of subjects who were mNY- / MRI- or MRI+.

Results:

As shown in Table 1, for AS studies requiring an mNY+ radiograph, 52.6% were eligible and 47.2% were ineligible.  For nr-AxSpA studies which required a mNY- radiograph, 70.9% were eligible and 29% were ineligible. Further, when nr-AxSpA mNY- subjects were assessed for MRI positivity per ASAS/OMERACT guidelines, 39.7% were MRI+ (eligible) and 60.3% were MRI- (ineligible).

Table 1:

Conclusion:

The screen failure rate was high for both AS (47.2%) and nr-AxSpA (29%) studies. Further, not all mNY- subjects initially categorized as nr-AxSpA were MRI+; 60.3% of the mNY- pool did not qualify per the ASAS/OMERACT criteria for inflammation of the SIJ. Given that MRI positivity is increasingly being used to enroll “true” non-radiographic axial SpA subjects the failure rate is noteworthy. Overall, the data suggests that not all subjects screened locally will qualify to enter the trial when the radiographic  criteria are applied centrally. This is due partly to the deliberate lack of clinical observations during central review of the SIJ imaging. In conclusion, these rates should be taken into consideration during prospective AS and nr-AxSpA trial design.