Rheumatologists should be on special alert for future radiographic progression in HLA-B27-positive male patients and those with a higher existing level of spinal damage in ankylosing spondylitis (AS), according to 12-year prospective data from the European Outcome in Ankylosing Spondylitis International Study (OASIS).
In the first longitudinal investigation of the course of radiographic damage at the group level, OASIS found that structural progression was largely unpredictable in individuals, often alternating with periods of acceleration and quiescence. It may occur in early as well as in advanced disease in patients at older ages. "Radiographic progression may be underestimated if the data are presented at the group level as a linear average of one mSASSS [] unit per year," wrote the authors in a study first published online in on Aug. 16, 2013.
While progression in individual patients was highly variable and occurred in patients with decades of symptom duration, mean 2-year progression was 2.0 (3.5) mSASSS units). About a quarter of patients showed no progression.
Led by rheumatology doctoral candidate of the in the Netherlands, the study followed 217 consecutive AS patients from the Netherlands, Belgium, and France as of 1996. The cohort was 70% male and 83% HLA-B27 positive, with a mean age of 43, a mean time since symptom onset of 20 years and a mean disease duration of 11 years, but in some cases more than 40 years' symptom duration.
Clinical data were collected every 6 months until year two, then annually until year four, and biennially thereafter. Cervical and lumbar radiographs (total 809) were taken biennially over 12 years, for a total of seven possible time points per patient.
With 186 patients evaluable, radiographs with <3 missing vertebral corners per segment were scored according to the mSASSS by two readers, who found at least one new syndesmophyte in no fewer than 60% of patients (reader one, 55%; reader two, 63%). Available 2-year progression scores were classified in categories of mSASSS units: 0; >0 and <1; >1; >2; >1 and <3; >3 and <5; and >5.
Despite individual variability, time was positively associated with damage in a linear fashion and at a rate of 0.98 mSASSS units per year. Radiographic progression was faster in men than in women (1.11 versus 0.69 mSASSS units/yr) and in HLA-B27-positive patients (1.03 versus 0.70 mSASSS units/yr). Progression was also faster in those with a baseline mSASSS of >10 -- the population median value -- compared with <10 (1.44 versus 0.69 mSASSS units/yr). HBLA-B27-positive men (but not women) had a significantly higher progression than HLA-B27-negative men (1.18 versus 0.69 mSASSS units/yr; interaction of HLA-B25, gender and time P=0.17).
Additionally, progression was higher in patients who were ever exposed to tumor necrosis factor inhibitors compared with those never exposed (1.54 versus 0.82 mSASSS units/yr; interaction P=0.041). It was independent of NSAID treatment, disease-related manifestations such as psoriasis and uveitis, and AS family history. It did not differ between the first and second 6 years of follow-up.
"Remarkably, radiographic progression seems to be entirely independent of disease or symptom duration," Ramiro told . "Periods of steep progression can be found at any time in the course of the disease, even decades after disease onset, and after periods of relative or complete quiescence." HLA-B27-positive men and patients with baseline mSASSS scores of >10 are at greater risk of progression.
Disclosures
Funding was provided by a grant the Fundacao para a Ciencia e Tecnologia.
The authors reported no competing interests.
Primary Source
Annals of the Rheumatic Diseases
Ramiro Sofia, et al "Evolution of radiographic damage in ankylosing spondylitis: a 12 year prospective follow-up of the OASIS study" Ann Rheum Dis 2015; DOI: 10.1136/annrheumdis-2013-204055