GHENT, BELGIUM: Strong numerical signal suggests that the addition of a selective cyclooxygenase-2 (COX-2) inhibitor to a tumor necrosis factor (TNF) inhibitor may reduce radiographic progression of the spine in patients with axial spondyloarthritis active radiographic (axSpA) for 2 years, although the results are not statistically significant.
Lead investigator and rheumatologist Fabian Proft, MD, based at Charité Medical University, Berlin, presented the study findings at the 13th International Congress on Spondyloarthritis.
Only 97 patients completed the study, and their follow-up period lasted two years, which is a relatively short period of time to determine the effects of an intervention that might affect the structural progression of the spine, Proft said.
“According to these data, I will not treat all my patients with celecoxibhe told this news organization. However, he added that “if I have a patient with residual symptoms on biologic DMARDs [disease-modifying antirheumatic drugs]and I feel they are at high risk for radiographic spinal progression and still have symptoms, so I would add an NSAID, and for that I would choose a selective COX-2 inhibitor based on the radiographic spinal progression data.”
Walter P. Maksymowych, MD, a rheumatologist at the University of Alberta, Calgary, discussed the study findings in an interview. “This is an important clinical question because we want to know if we should add an anti-inflammatory in patients receiving biologic therapies. There has been a long debate and investigation as to whether anti-inflammatories could prevent new bone formation and thus prevent disease progression. .”
He went on to acknowledge that there was no statistically significant difference in the primary endpoint (change in modified Stoke’s ankylosing spondylitis spinal score). [mSASSS]) between the groups, but added that “there was a considerable numerical difference, and I think this leaves the community somewhat dry without a definitive answer. However, I am concerned about whether there was an adequate sample size to address the study questions.”
Add or not add a selective COX-2 inhibitor to the TNF inhibitor in the treatment of AxSpA
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 radiographically active axSpA.
“To date, we don’t have many treatments with evidence of slowing spinal radiographic progression in axSpA,” said Proft. “There was one study that showed an effect of celecoxib, but another with diclofenac which failed to show any effect. As a result, the hypothesis was raised that perhaps there was a selective inhibitory effect of COX-2.”
To investigate this further, Proft selected patients with high radiographic activity of axSpA disease (Bath Ankylosing Spondylitis Disease Activity Index). [BASDAI] ≥ 4) and with existing structural changes, both recognized risk factors for further progression. Participants had to have 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. The duration of axSpA was unlimited.
Three radiographic readers were blinded to all clinical data and chronology. The primary endpoint was 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 golimumab alone (50 mg subcutaneously every 4 weeks) for the first 12 weeks, and then only those patients with a good clinical response (n = 109) entered phase two of the study, at which time they were randomized 1 : 1st 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 combination therapy and 52 completed monotherapy.
No statistical significance but a numerical difference was found
“The primary outcome, which was the change in mSASSS score, clearly shows a numerical difference between the combination arm of 1.1 and the monotherapy arm of 1.7 points, showing more structural progression in the monotherapy arm. monotherapy compared to the combination arm,” reported Proft. However, he highlighted that this difference did not reach statistical significance.
New syndesmophytes occurred in 25% with monotherapy and 11.1% with combination therapy. Again, this difference did not reach statistical significance.
“This could be due to sample size, but also to length of follow-up because longer follow-up [given structural changes occur relatively slowly] could have shown a bigger difference,” said Proft.
Clinical data, based on CRP ankylosing spondylitis disease activity score and BASDAI, showed that both groups responded very well to therapy and no differences were observed between the two groups in terms of clinical parameters.
“When we add a drug, and we know that NSAIDs may have safety concerns, it’s important that we don’t see any statistically significant serious adverse events between patient groups,” Proft noted.
There were no significant differences in adverse events between monotherapy and combination therapy. There were 162 infections in the combination arm and 150 in the monotherapy arm. Combination therapy caused seven serious adverse events and monotherapy caused five adverse events.
Proft added that four patients dropped out of the combination group, compared to just one in the monotherapy group, with a variety of different reasons for discontinuations.
The study was supported by a grant from the German Ministry of Education and Research, and golimumab was provided free of charge by Merck Sharp & Dohme. Proft reported working in speaker’s bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; serving as a consultant to Novartis; and receive grants or research support from Novartis, UCB and Lilly. Maksymowych declared no relevant conflicts of interest.
This article originally appeared on MDedge.compart of the Medscape professional network.