Four risk factors predicted the progression from nonradiographic to radiographic axial spondyloarthritis (axSpA) over a 5-year period in the PROOF study, a global, real-world, prospective, observational study carried out in 29 countries across six different geographic regions.
The predictors of progression within 5 years, based on the presence of radiographic sacroiliitis, included male gender, fulfillment of imaging criteria, HLA-B27 positivity, and a good response to NSAIDs, Denis Poddubnyy, MD, professor of rheumatology at Charité-Universitätsmedizin Berlin, said in his presentation of the study results at the annual European Congress of Rheumatology.
“In this study, 16% of nonradiographic axSpA patients progressed to radiographic axSpA within 5 years, with the mean time to disease progression of 2.4 years,” he said. PROOF (Patients with Axial Spondyloarthritis: Multicountry Registry of Clinical Characteristics) wasto compare demographic and clinical characteristics of patients with axSpA across geographic regions.
In this particular analysis, Dr. Poddubnyy and colleagues aimed to track structural damage progression in the sacroiliac joint over time, as he explained in an interview. The study enrolled 2,633 adults with chronic back pain lasting for at least 3 months with onset before the age of 45 years. This analysis included patients diagnosed with axSpA who also fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA.
Both baseline and follow-up radiographs of sacroiliac joints were evaluated for those with an initial diagnosis of nonradiographic axSpA by two central readers; in cases when the readers disagreed on the classification – either nonradiographic or radiographic axSpA – images were adjudicated by a third reader. Radiographic progression from nonradiographic to radiographic axSpA was evaluated over the next 5 years.
Among all enrolled patients, 82% (n = 2,165) were diagnosed with axSpA and fulfilled the ASAS classification criteria. Of 1,612 who were classified by central reading, 65% had radiographic axSpA while the remaining 35% had nonradiographic axSpA. About 78% of those with nonradiographic axSpA fulfilled the ASAS classification criteria because of positive findings on imaging plus one or more features of spondyloarthritis. The other 22% were classified according to clinical criteria.
A total of 246 nonradiographic axSpA patients who had one or more follow-up radiographs of the sacroiliac joint were included in the current analysis. In this smaller group of patients, progression from the initial diagnosis of nonradiographic to radiographic axSpA at any one point over the 5-year follow-up occurred in 40 patients (16%) at a range of between 0.9 and 5.1 years.
“Females are more likely to stay in the nonradiographic stage than males,” Dr. Poddubnyy noted. Indeed, male gender conferred an over-threefold higher risk of radiographic progression, compared with females (hazard ratio, 3.16; 95% confidence interval, 1.22-8.17; P = .0174). Fulfillment of imaging criteria – in other words, the presence of inflammation on MRI – was also a strong predictor of progression, conferring an over-sixfold risk of radiographic progression (HR, 6.64; 95% CI, 1.37-32.25; P = .0188).
Interestingly, a good response to NSAIDs – the mainstay treatment for both nonradiographic and radiographic axSpA – was also significantly associated with radiographic progression, conferring an over-fourfold risk among those with an initial diagnosis of nonradiographic axSpA (HR, 4.66; 95% CI, 1.23-17.71; P = .0237). And in a separate model, HLA-B27 positivity was significantly associated with radiographic progression, conferring a nearly fourfold higher risk of progression (HR, 3.99; 95% CI, 1.10-14.49; P = .0353).
Asked if rheumatologists need to manage patients with nonradiographic axSpA differently than those with radiographic progression, Dr. Poddubnyy said that there was a small difference between the two in that biologics such as interleukin-17 inhibitors or Janus kinase inhibitors are approved for radiographic axSpA, whereas they are not approved for nonradiographic disease despite some off-label use. “We need to have high levels of symptoms plus nonresponse to NSAIDs and then we can prescribe a biologic,” he added.
For patients with nonradiographic axSpA, patients similarly need to have a high symptom burden and a nonresponse to NSAIDs, but in addition, physicians need to demonstrate objective signs of inflammatory activity, such as an elevated C-reactive protein level or the presence of inflammation on MRI before moving on the next level.
AbbVie funded the PROOF study. Dr. Poddubnyy declared receiving speaker bureau fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, and UCB. He has also served as a consultant for AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Pfizer, Samsung Bioepis, and UCB, as well as research support from AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, and Pfizer. A number of coauthors also disclosed financial relationships with these and other pharmaceutical companies.