Etanercept With or Without Celecoxib Superior to Celecoxib Alone on Improving Inflammation of MRI After One Year Treatment of Active Ankylosing Spondylitis：A Multi-Center, Open Label, Randomized Clinical Trial

Background: The combined effect of etanercept and celecoxib on active ankylosing spondylitis (AS) on inflammation alleviation is unknown when compared with monotherapy. We aimed to investigate the efficacy and safety of clinical, magnetic resonance imaging (MRI) changes in active AS patients with etanercept and celecoxib alone/combined treatment.  Methods: We did an open-label, randomized controlled trial at three rheumatology centers in China. AS patients were eligible if their BASDAI ≥ 4 or ASDAS≥ 2·1, CRP＞6 mg/L or ESR 28 mm/1 st hour. Enrolled patients were randomly assigned in a 1:1:1 ratio to receive celecoxib 200mg bid (group A), etanercept 50mg qw (group B) or combined therapy with celecoxib and etanercept (group C) for 52 weeks. Assessors were masked to treatment allocation. The primary outcomes were SPARCC change of sacroiliac joint (SIJ) and spine, proportion of patients achieving ASAS20 response at 52 weeks. Findings: Between Sept 2014 and Jan 2016, we randomly assigned 150 patients (mean age, 32·4 years; mean disease duration, 109 months), 133 (88·6%) completed the study. SPARCC inflammation scores of SIJ and spine decreased in three groups and significant differences were found between group C and group A (between group difference: -6·33, 95%CI (-10·56, -2·10) for SIJ; -9·53, 95%CI (-13·73, -5·33) for spine), between group B and group A (between group difference: -5·02, 95%CI (-9·29, -0·76) for SIJ; -5·80, 95%CI (-10·04, -1·57) for spine). ASAS20 response rate were 44%, 58% and 84% in group A, B, C respectively and significant difference was only found between group C and group A. Interpretation: Etanercept with or without celecoxib decreases inflammation detected by MRI at one-year compared to celecoxib alone in active AS patients. The combination of etanercept and celecoxib was superior to celecoxib alone for the primary clinical response. Trial Registration: This trial is registered with ClinicalTrials.gov, number NCT01934933. Funding Statement: This study was funded by Pfizer Ltd. Declaration of Interests: No competing interests exist. Ethics Approval Statement: Ethics approval has been received from the medical research ethics committee of third affiliated hospital of Sun Yat-sen University. Informed written consent was obtained from all participants. The protocol was reviewed and approved by each site’s institutional review board or independent ethics committee.