Discussion
inflammation, SI joint damage, axSpA, sacroiliitis
DISEASE PROGRESSION, INFLAMMATION, DISEASE, MINOR, NR-AXSPA, SACROILIITIS, JOINT INFLAMMATION
This exploratory analysis from the PREVENT study evaluated radiographic changes and spinal inflammation in patients with active nr-axSpA over a period of 2 years. This is one of the largest imaging datasets in patients with nr-axSpA available to date. The overall radiographic changes, along with any changes in spinal inflammation, in a population of patients on an effective biologic therapy were minimal over time, while a reduction in SI joint inflammation was observed as previously reported [Most of the patients in the secukinumab group (87.7%), as well as those originally randomized to the placebo group (85.6%), did not have an increase in total sacroiliitis score above the SDC on SI joint radiographs, indicating no radiographic progression over 2 years. The SDC for the total sacroiliitis score was 0.46. Notably, given that the minimum possible change on mNY grading scale is 1, the smallest change that can be observed in an individual patient when considering the average score by 2 readers is 0.5. None of the patients in either group had an increase in total sacroiliitis score of > 2, and only few had an increase of > 1 (1.1% in the secukinumab group and 2.2% in the placebo group). Furthermore, the proportion of patients who had an increase in the total sacroiliitis score greater than the SDC was similar to the proportion of patients who had a decrease in the score of similar magnitude, suggesting that the observed change may be attributed to reader variability rather than disease progression.As per the eligibility criteria, any patient with mNY-positive status at screening based on the eligibility read by a single reader was excluded from the study. However, when the same images from screening were scored again alongside post-baseline images at week 104, by readers blinded to the sequence of imaging, some of the radiographs were scored as mNY-positive. The poor-to-moderate intra-rater and inter-rater reliability of SI joint damage assessment according to the mNY criteria are well described [While earlier studies suggested low but evident progression in early axSpA, more recent studies report even lower rates of radiographic SI joint structural progression. In the RAPID-axSpA study, limited changes in SI joint grading were observed after 4 years in patients treated with certolizumab: 4.5% (2 of 44) of patients who were mNY-negative at baseline fulfilled the mNY criteria at week 204 and 4.3% (4 of 93) of patients who were initially mNY-positive were evaluated as mNY-negative at week 204 [Lower rates of progression reported in more recent studies may reflect greater awareness of the measurement error in radiograph scoring leading to the implementation of central reading with more than 2 readers and also acknowledging the measurement error in the analysis. Another potential reason for low to negligible progression rates reported here and in other recent studies could be the nr-axSpA population recruited into these clinical trials, who may present with less severe disease and have earlier access to biologic treatment.With regard to the mSASSS score, most patients in both groups showed no progression to week 104. While none of the patients in either group had an mSASSS total score increase of > 5, around 1% had an increase of > 2. The mean change in mSASSS score was 0.04 in the secukinumab group (0.68 at baseline). Previous studies have similarly reported limited spinal progression in patients with nr-axSpA. In the RAPID-axSpA study, which reported 4-year imaging outcomes, the mean mSASSS change was − 0.01 (95% confidence interval [CI], − 0.19 to 0.17) from baseline to week 96 and 0.06 (95% CI, − 0.17 to 0.28) to week 204 in patients with nr-axSpA treated with certolizumab pegol [In the present study, approximately 15% of patients had syndesmophytes at baseline identified by at least 1 reader (6% when reader agreement was required). Similarly, 20% of the nr-axSpA patients in the RAPID-axSpA study, 9% of patients in the Swiss Clinical Quality Management cohort (readers’ agreement was required in both studies), and 7% of patients in the DESIR cohort (2 of the 3 readers were required to identify the syndesmophyte) had syndesmophytes at baseline, suggesting that the process of structural damage starts early in the disease at least in some patients [Syndesmophyte formation is thought to be mainly associated with r-axSpA [This study had some limitations. Patients were allowed to switch to open-label secukinumab or standard of care leading to a lack of placebo control after 20 weeks. The analyses of images were conducted on patients who continued on the study, thus were likely to respond well to the treatment introducing a potential bias. Also, in this study, inter-rater reliability was modest at best. However, this is not surprising in sacroiliitis assessment where low-to-moderate inter-rater/intra-rater reliability has been reported in previous studies [The value of minor effects of biological disease-modifying anti-rheumatic drugs (DMARDs) [