Nearly one-quarter of patients with ankylosing spondylitis experienced disease progression over time, with male sex, presence of baseline damage, active disease state, and higher inflammatory markers predictive of spinal progression, while treatment with tumor necrosis factor (TNF) inhibitors slowed the progression rate, say researchers recently writing in Arthritis Care & Research.
Nearly 20 percent to 50 percent of ankylosing spondylitis patients have been reported to show some degree of spinal progression in two years of follow-up. Several predictors of spinal disease progression have been described, including baseline structural damage, higher inflammatory burden, male sex, positivity for HLA-B27, and smoking. Non-steroid anti-inflammatory drugs (NSAIDs) and TNF inhibitor treatments are the cornerstone therapies in the management of ankylosing spondylitis, with some reports suggesting a beneficial effect on structural damage.
“Assessment of ankylosing spondylitis-related structural changes longitudinally is essential for understanding the natural course of progression and its underlying factors. This could help identify the mechanisms responsible for progression and thereby personalizing treatment,” wrote the authors of the study, led by Nigil Haroon, M.D., Ph.D., D.M., of Toronto Western Hospital in Canada.
In this longitudinal observational cohort study of 350 ankylosing spondylitis patients (mean age 38.4 years, 76 percent male, mean symptom duration 14.9 years, syndesmophytes present 46.6 percent), researchers sought to identify progression rates, and factors predictive of spinal progression. A secondary aim was to assess the effect of TNF inhibitors on radiographic progression. Radiographic damage was assessed by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and change of two mSASSS units in two years was defined as progression.
The mean mSASSS increased from 9.3 (15.8) units at baseline to 17.7 units by year six. Change in mSASSS scores between the zero to two, two to four and four to six years were 1.23, 1.47, and 1.52 units, respectively, and the corresponding rates of progression were 24.3 percent, 26.9 percent, and 19.7 percent. Male sex (HR 2.46, 95%CI 1.05, 5.76), presence of baseline damage (HR 7.98, 95%CI 3.98, 16), increased inflammatory markers (logCRP; HR 1.35, 95%CI 1.07, 1.70) and TNF inhibitor use (HR 0.82, 95%CI 0.70, 0.96) were predictive of radiographic progression.
“At least one-year use of TNF inhibitor therapy was associated with decreased progression rate in the next radiography interval and 20 percent reduction in the rate of spinal progression compared to non-TNF inhibitor treated patients,” the authors wrote.
This effect remained significant even after correction of predictors of radiographic progression including sex, baseline damage, disease activity and inflammation markers, and the finding "confirms our earlier multicenter study and other subsequent longer-term studies, that TNF inhibitors have a disease-modifying effect in ankylosing spondylitis,” the authors wrote.
“After correcting for time, each unit increase in ASDAS-CRP resulted in a 0.45 increase in the yearly slope of mSASSS,” the authors wrote. “Patients with high and very high disease activity states were more likely to progress over time.”
A limitation of the study was the reliance on mSASSS for assessing progression, which may underestimate the changes, as only the anterior vertebral corners of the cervical and lumbar spine are included.
Ismail Sari, Seunghun Lee, George Tomlinson, et al. “Factors Predictive of Radiographic Progression in Ankylosing Spondylitis.” Arthritis Care & Research. November 1, 2019. doi: 10.1002/acr.24104