Etanercept/celecoxib on improving MRI inflammation of active ankylosing spondylitis: A multicenter, open-label, randomized clinical trial

Liudan Tu, Minjing Zhao, Xiaohong Wang, Qingcong Kong, Zena Chen, Qiujing Wei, Qiuxia Li, Qinghong Yu, Zhizhong Ye, Shuangyan Cao, Zhimin Lin, Zetao Liao, Qing Lv, Jun Qi, Ou Jin, Yunfeng Pan, Jieruo Gu, Liudan Tu, Minjing Zhao, Xiaohong Wang, Qingcong Kong, Zena Chen, Qiujing Wei, Qiuxia Li, Qinghong Yu, Zhizhong Ye, Shuangyan Cao, Zhimin Lin, Zetao Liao, Qing Lv, Jun Qi, Ou Jin, Yunfeng Pan, Jieruo Gu

Abstract

Objective: To investigate the efficacy and safety of clinical, magnetic resonance imaging (MRI) changes in active ankylosing spondylitis (AS) patients with etanercept and celecoxib alone/combined treatment.

Methods: A randomized controlled trial was conducted in three medical centers in China. Adult AS patients with BASDAI ≥4 or ASDAS ≥2.1, CRP >6 mg/L, or ESR 28 mm/1st hour were randomly assigned (1:1:1 ratio) to celecoxib 200 mg bid or etanercept 50 mg qw or combined therapy for 52 weeks. The primary outcomes were SPARCC change of the sacroiliac joint (SIJ) and spine and the proportion of patients achieving ASAS20 response at 52 weeks.

Results: Between September 2014 and January 2016, we randomly assigned 150 patients (mean age, 32.4 years; mean disease duration, 109 months), and 133 (88.6%) completed the study. SPARCC inflammation scores of the SIJ and spine decreased in the three groups, and significant differences were found between the combined group and the celecoxib group [between-group difference: -6.33, 95% CI (-10.56, -2.10) for SIJ; -9.53, 95% CI (-13.73, -5.33) for spine] and between the etanercept group and the celecoxib group [between-group difference: -5.02, 95% CI (-9.29, -0.76) for SIJ; -5.80, 95% CI (-10.04, -1.57) for spine]. The ASAS20 response rates were 44%, 58%, and 84% in the celecoxib, etanercept, and combined groups, respectively, and a significant difference was only found between the combined and the celecoxib groups.

Conclusion: Etanercept with or without celecoxib decreases inflammation detected by MRI at 1 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.

Clinical trial registration: ClinicalTrials.gov, identifier NCT01934933.

Keywords: MRI; NSAIDs; biological therapies; inflammation; spondyloarthritis.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Tu, Zhao, Wang, Kong, Chen, Wei, Li, Yu, Ye, Cao, Lin, Liao, Lv, Qi, Jin, Pan and Gu.

Figures

Figure 1
Figure 1
Study design and patient disposition.
Figure 2
Figure 2
Mean change from baseline for (A) SPARCC MRI SIJ score and (B) SPARCC MRI spinal score. The mixed-effect model was used for the comparison between groups. *P < 0.05. Mean (SD) baseline values: (A) 8.63 (11.67) for CELE, 8.28 (13.65) for ENT, and 9.63 (13.08) for ENT+CELE; (B) 24.61 (14.05) for CELE, 24.14 (10.76) for ENT, and 27.80 (13.26) for ENT+CELE. Within-group P-value between baseline and week 52 from the mixed-effect model: <0.0001 for all in the SPARCC MRI SIJ and SPARCC MRI spinal scores. Within-group P-value between baseline and week 24 from the mixed-effect model: <0.0001 for all in the SPARCC MRI spinal score, <0.0001 for ENT and ENT+CELE in the SPARCC MRI SIJ score, and no significant difference for CELE in the SPARCC MRI SIJ score. ENT, etanercept; CELE, celecoxib; SIJ, sacroiliac joint; SPARCC, Spondylitis Research Consortium of Canada.
Figure 3
Figure 3
Proportion of patients achieving (A) ASAS20 response, (B) ASAS40 response, (C) ASAS50 response, (D) ASAS70 response, (E) ASDAS major improvement, and (F) ASDAS clinical important improvement in the three groups over 52 weeks. Population is modified intention to treat, non-responder imputation (NRI). The actual number of patients is shown as the observed case (OC). P-values for differences in the results between groups at any timepoint are from the Kruskal–Wallis test, and the adjusted P-value for significance is 0.008 in multiple comparisons between groups. ASAS, Assessment of SpondyloArthritis International Society; ASDAS, Ankylosing Spondylitis Disease Activity Score; ENT, etanercept; CELE, celecoxib; ns, non-significant. *, significant difference was found between the etanercept and celecoxib groups only at week 2. #, no significant difference was found between the etanercept + celecoxib and celecoxib groups at week 52. &, significant differences were found between etanercept and celecoxib groups at weeks 2, 6, 12, and 36.

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