The benefits of treatment with TNF-alpha inhibitors in reducing spinal radiographic progression in ankylosing spondylitis became most evident 6-8 years after the biologic therapy was initiated, according to findings from a prospective observational cohort study.
The study enrolled 210 consecutive patients from the Groningen Leeuwarden AS (GLAS) cohort who initiated treatment with TNF-alpha inhibitors during 2004-2012 and who received baseline and biannual radiographs over the 8-year follow-up.
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radiograph of ankylosing spondylitis
In patients with complete modified Stoke AS Spine Score (mSASSS) data over 8 years of follow-up, the estimated mean spinal radiographic progression was 2.3 points during the first 2 years of treatment and then declined steadily to 1.4 in years 2-4, 1.0 in years 4-6 and 0.8 in years 6-8. This decrease was seen even after adjusting for baseline mSASSS, the presence of syndesmophytes, sex, HLA-B27 status, age, symptom duration, smoking duration, body mass index, disease activity, and NSAID use.
Patients with longer follow-up also showed more use of NSAIDs, higher C-reactive protein levels, and more spinal radiographic damage at baseline. There were, however, significant improvements in all disease activity measures as soon as patients began treatment, and patients also showed a rapid decrease in NSAID use over time, said Fiona Maas of the University Medical Center Groningen (Netherlands) and her associates.
Multiple studies have been conducted into the impact of TNF-alpha inhibitors on spinal radiographic progression in ankylosing spondylitis, but the results have been subject to some debate, the investigators noted.
“It is known that radiographic progression in AS is overall slow and highly variable between patients,” they wrote. “Therefore, differences in patient numbers at the different time points during follow-up can affect the outcome measure of interest, in this case radiographic progression.”
In this study, researchers saw a straightforward linear progression of disease in the first 4 years after treatment was initiated but a deflection from linear progression in years 6 and 8.
“These results may refer to a delayed effect of TNF-alpha inhibitors on radiographic progression and support the TNF brake hypothesis,” they wrote, suggesting that the long-term inhibition of inflammation with TNF-alpha inhibitors diminishes new bone formation over time in patients with longstanding disease.
The GLAS cohort was supported Pfizer. Four authors declared research grants and consulting fees from pharmaceutical companies including Pfizer. No other conflicts of interest were declared.