New research presented this week at ACR Convergence 2022, the annual meeting of the American College of Rheumatology, showed that the combination of a nonsteroidal anti-inflammatory drug and a TNF inhibitor did not significantly slow radiographic spinal progression in patients with radiographic axial spondyloarthritis (Abstract #0546).
Axial spondyloarthritis (axSpA) is a chronic inflammatory condition with two subgroups: non-radiographic axial spondyloarthritis and radiographic axial spondyloarthritis, the advanced stage of the disease. Radiographic axial spondyloarthritis was previously known as ankylosing spondylitis. Unlike non-radiographic axSpA, radiographic axSpA is marked by evidence of structural damage on radiographs. The main clinical symptom is back pain, with active inflammation in the sacroiliac joints and spine and, in some patients, excessive new bone formation that can impair function.
Reducing clinical burden and preventing disability can probably be best achieved by early and appropriate treatment targeting both inflammation and new bone formation.”
Fabian Proft, MD, rheumatologist and principal investigator at Charité Universitätsmedizin Berlin and lead author of the study
Continuous use of celecoxib, a selective nonsteroidal anti-inflammatory drug (NSAID), may be associated with less radiographic progression in patients with radiographic AxSpA. Biologic disease-modifying antirheumatic drugs (DMARDs) are often used to treat high disease activity, and the extent to which they affect structural damage remains ambiguous, says Dr. Proft.
“The effect on radiographic progression in radiographic AxSpA of a combination treatment of biologic DMARD plus NSAID has not been investigated so far. We wanted to assess the impact of celecoxib when added to a biologic DMARD. This study used the necrosis factor inhibitor (TNFi ) golimumab with celecoxib and compared it with golimumab alone in progressive structural damage to the spine over two years in patients with radiographically active axSpA”.
Eligible patients for this prospective randomized controlled trial were recruited from centers throughout Germany. All had a clinical diagnosis of radiographic AxSpA, met the modified New York criteria for ankylosing spondylitis, had high disease activity despite NSAID therapy, and had at least one additional risk factor for radiographic progression (protein Elevated reactive C and/or existing syndesmophytes). [bony growths inside spinal ligaments]).
The trial had two phases. The first was a 12-week lead-in phase in which participants received 50 mg golimumab every four weeks. Those who had a good clinical response were equally randomized to the combination group (celecoxib 400 mg daily plus golimumab) or the golimumab alone control group for 96 weeks.
Ninety-seven of the original 109 randomized patients completed the trial. Patients in the combination group had a change in Stoke’s ankylosing spondylitis spine score of 1.1 points compared to a change of 1.7 in the control group. Three blinded readers identified new syndesmophytes in 11% of the combination group versus 25% of the golimumab-alone group, respectively. During the study, seven serious adverse events were reported in the combination group compared to five in the control group. Two occurred during the shooting phase.
In general, the differences observed between combination therapy and monotherapy did not reach statistical significance.
“We didn’t expect that,” says Dr. Proft. “[It might be possible that] the findings would have become statistically significant with a larger sample size or longer follow-up, such as four years. [But] Based on our data, continuous treatment with NSAIDs in addition to a biologic DMARD solely to inhibit future radiographic progression cannot be recommended in general. However, the observed effect of a combination treatment might be relevant in patients at high risk of radiographic progression or with residual symptoms despite DMARD biologic therapy.”