BERLIN – Consistent daily use of full-dose NSAIDs significantly slows radiographic spinal progression in ankylosing spondylitis patients but only in the subgroup with risk factors for progression – namely, syndesmophytes and elevated C-reactive protein or erythrocyte sedimentation rate.
Ankylosing spondylitis (AS) patients without these risk factors have such a low rate of radiographic spinal progression over 2 years of follow-up that their risk is unaffected by how consistently they use NSAIDs, Dr. Denis Poddubnyy reported at the annual European Congress of Rheumatology.
Dr. Denis Poddubnyy
These conclusions are based on two studies presented at the meeting: one by Dr. Poddubnyy involving participants in a prospective registry known as the German Spondyloarthritis Inception Cohort, and the other a new post hoc analysis of data from the first, and to date the only, randomized controlled trial of the impact of consistently high versus as-needed use of NSAIDs on radiographic spinal progression in patients with AS.
"I think these data might change future treatment guidelines as we move along the way to more individualized treatment for patients with ankylosing spondylitis. Symptomatic patients who require NSAIDs would benefit most from the medication if they also have risk factors associated with radiographic progression," said Dr. Poddubnyy of Charité Hospital in Berlin.
He presented a study of 164 German registry participants, all with definite early axial spondyloarthritis. Eighty-eight patients met diagnostic criteria for axial AS, and the other 76 had nonradiographic axial spondyloarthritis. They were selected from the registry because they all had 2 years of serial spinal x-rays and detailed information on their NSAID use during that period. Axial spinal x-rays were independently assessed by two blinded readers using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). NSAID intake was rated using a scoring system developed by the Assessment of Spondylarthritis International Society (Ann. Rheum. Dis. 2011;70:249-51).
Sixty-four AS patients were categorized as having low NSAID intake, defined as less than 50% of daily full-dose use. These patients took NSAIDs on an as-needed basis. They had a substantial rate of radiographic progression of their spinal disease: a mean 0.96-point increase in mSASSS over the course of 2 years from a baseline score of about 6. In contrast, patients with high NSAID intake – that is, at least 50% of full-dose therapy 7 days a week – had virtually no radiographic progression, with a mean 0.02-point increase. Consistent use of full-dose NSAIDs had a beneficial structure-modifying effect on new bone formation, the rheumatologist observed.
A multivariate logistic regression analysis identified two independent risk factors for substantial radiographic spinal progression: the presence of syndesmophytes on the baseline spinal x-ray and a consistently elevated C-reactive protein (CRP) level. Baseline syndesmophytes were by far the most potent risk factor, with an associated 6.8-fold increased risk. AS patients with one or both of these risk factors and low NSAID intake averaged a 4.36-point increase in mSASSS scores over 2 years, while high NSAID users with risk factors averaged a nonsignificant 0.14-point increase.
"Remarkably, in patients without risk factors for progression we saw nearly no progression, and no difference between high and low NSAID intake," according to Dr. Poddubnyy.
In response to an audience question, he estimated that about 30% of AS patients have risk factors for radiographic spinal progression.
In the 76 registry patients with nonradiographic axial spondyloarthritis, the level of NSAID use made no difference in terms of the rate of change in mSASSS scores. "At this stage, radiographic progression in these patients is probably due to forces other than new bone formation," he explained.
Dr. Poddubnyy noted that while this was not a randomized trial, the registry findings were confirmed in another study presented during the congress. This was a Dutch post hoc secondary analysis of data from the only randomized prospective clinical trial to date demonstrating that continuous NSAID intake over a 2-year period was associated with significantly less radiographic spinal progression than as-needed use (Arthritis Rheum. 2005;52:1756-65).
The new post hoc analysis of 150 AS patients randomized to continuous or as-needed celecoxib showed that retardation of radiographic spinal progression through high intake of NSAIDs was essentially confined to patients with either of two baseline risk factors for radiographic progression: a consistently elevated CRP or an elevated erythrocyte sedimentation rate (ESR).
The Dutch investigators found that patients with a high baseline CRP had a 13% rate of substantial radiographic disease progression during 2 years if they used celecoxib continuously compared with a 38% rate with as-needed use. Those with an elevated ESR had a 22% risk of substantial progression if they used the NSAID continuously but a 49% risk if they took celecoxib on an as-needed basis.