GHENT, BELGIUM – A strong numerical signal suggests the addition of a selective cyclooxygenase-2 (COX-2) inhibitor to a tumor necrosis factor (TNF) inhibitor can reduce spinal radiographic progression in patients with active radiographic axial spondyloarthritis (axSpA) over 2 years, although results are not statistically significant.
Becky McCall/MDedge News
Dr. Fabian Proft
Lead researcher and rheumatologist, Fabian Proft, MD, based at Charité University Medicine, Berlin, presented the findings of the study at the 13th International Congress on Spondyloarthritides.
Only 97 patients completed the study, and its follow-up period lasted 2 years, which is a relatively short period of time in which to determine the effects of an intervention that might affect structural progression of the spine, Dr. Proft said.
“Based on these data, I won’t treat all my patients with celecoxib,” he told this news organization. However, he added that, “If I have a patient with residual symptoms under biological DMARDs [disease-modifying antirheumatic drugs], and I feel they are at high risk of radiographic spinal progression and they still have symptoms, then I would add in an NSAID – and for that I’d choose a selective COX-2 inhibitor based on radiographic spinal progression data.”
Walter P. Maksymowych, MD, rheumatologist from the University of Alberta, Calgary, commented on the study findings in an interview. “This is an important clinical question because we want to know whether we should be adding an anti-inflammatory in patients who are on biologic therapies. There’s been a long debate and investigation into whether anti-inflammatories might prevent new bone formation and thereby prevent disease progression.”
Dr. Walter P. Maksymowych
He went on by acknowledging that there was no statistically significant difference in the primary endpoint (change in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]) between the groups, but added that, “there was a sizable numerical difference, and I think this leaves the community somewhat hanging dry without a definitive answer. However, I do have concerns about whether there was an adequate sample size to address the study question.”
To add or not to add a selective COX-2 inhibitor to TNF inhibitor in axSpA treatment
The study aimed to investigate the effect of a selective COX-2 inhibitor when added to anti-TNF therapy with golimumab (Simponi), compared with golimumab therapy alone, on the progression of spinal structural damage over 2 years in patients with active radiographic axSpA.
“To date, we don’t have many treatments with evidence of reducing spinal radiographic progression in axSpA,” Dr. Proft said. “There was one study showing an effect of celecoxib, but another with diclofenac that failed to show any effect. As a result, there was a hypothesis that perhaps there was a selective COX-2 inhibitor effect.”
To investigate this further, Dr. Proft selected patients with high radiographic axSpA disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4) and with existing structural changes – both recognized risk factors for further progression. Participants had to have either an elevated C-reactive protein (CRP) > 5 mg/L and/or ≥ 1 syndesmophyte at screening, as well as a history of inadequate response to at least two DMARDs. Other patient risk factors for radiographic spinal progression included male gender and smoking. Duration of axSpA was unlimited.
Three radiographic readers were blinded for all clinical data and chronology. The primary endpoint was the change in mSASSS, while secondary endpoints were the presence of new syndesmophytes and clinical outcomes including activity, function, mobility, and health-related quality of life, as well as safety assessments.
Patients were treated with only golimumab (50 mg subcutaneous every 4 weeks) for the first 12 weeks and then only those patients with a good clinical response (n = 109) went into phase two of the study, at which point they were randomized 1:1 to golimumab monotherapy (control, 50 mg subcutaneous every 4 weeks), or golimumab (50 mg subcutaneous every 4 weeks) plus celecoxib (400 mg once daily) for 2 years. Radiographs were taken at baseline (week 0) and after 2 years. A total of 45 patients completed the combination therapy and 52 completed the monotherapy.