Objectives To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS).
Methods Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis.
Results A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97).
Conclusion TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity.
- ankylosing spondylitis
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CM and AS contributed equally.
Handling editor Tore K Kvien
Contributors AC, AS and CM designed the study. All investigators substantially contributed to the acquisition, analysis or interpretation of data. AC wrote the article, and all coauthors revised the manuscript critically for important intellectual content. CM and AS were responsible for the implementation of the statistical analyses. AC had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors agreed on the final content of the submitted manuscript.
Funding The SCQM Foundation is supported by the Swiss Society of Rheumatology and by AbbVie, Bristol-Myers-Squibb, Celgene, Janssen-Cilag, Merck Sharp & Dohme, Novartis, Pfizer, Roche and UCB and has received project-based financial supports from the Arco Foundation, Switzerland, as well as from the Swiss Balgrist Society, Switzerland. This study was supported by the Stiftung für Rheumaforschung and a research grant from the investigator initiated studies program of Merck Sharp & Dohme. The study sponsors had no role in the study design or in the collection, analysis or interpretation of the data, the writing of the manuscript or the decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by the study sponsors.
Competing interests JB has received consulting fees from Merck Sharp & Dohme, Pfizer and Roche. AC has received consulting and/or speaking fees from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Merck Sharp & Dohme, Novartis, Pfizer and UCB. MJN has received consulting and/or speaking fees from Abbvie, Novartis and Pfizer. DvdH has received consulting fees from Abbvie, Amgen, Astellas, AstraZeneca, BMS, Boeringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB and is director of Imaging Rheumatology BV. UW has received speaking fees from AbbVie. AS, GT, LMW, MC, MdH, PE, PZ, RBML, RK, RM and XB
declare no conflict of interest. No non-financial conflicts of interest exist for any of the authors.
Patient consent Obtained.
Ethics approval Ethics Committee of the Canton of Zurich.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All data supporting our findings are shown in the article.
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