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Biological disease-modifying anti-rheumatic treatment delayed spinal fractures related to ankylosing spondylitis: National multi-registry cohort study from the Swedish Patient Registry and the Swedish Prescribed Drugs Registry
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.ORCID iD: 0000-0002-2724-6372
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective

Ankylosing spondylitis (AS) is associated with increased spinal fracture risk due to loss of elasticity in spinal motion segments. With the introduction of biological disease modifying anti-rheumatic drugs (bDMARD) treatment for AS patients the individual course of the disease has been decelerated.  This study aims to clarify whether the improved medical therapy reduced the spinal fracture incidence.

Methods

Included were all patients with the diagnosis of AS 1987 to 2014 from the Swedish Patient Registry. From the Swedish Prescribed Drug Registry the Anatomical Therapeutic Chemical codes for bDMARD, non-steroidal anti-inflammatory drugs (NSAID), methotrexate (MTX) and sulfasalazine were extracted and numbers of prescriptions and years of treatment counted since 2005.

Results                

12297 patients with ankylosing spondylitis were included between 1987 and 2014 (age 67±19, 67% male). Of these 291 had spinal fractures between 2011 and 2014. The number of prescriptions of bDMARD increased during the last decade, but not of MTX, sulfasalazine and NSAID. 64% of all AS patients used NSAID, 13% used bDMARD, 13% used MTX, and 10% used sulfasalazine. A multivariate analysis of patients with spinal fractures 2011-2014 found bDMARD delaying spinal fracture debut by 1.24 years per year of bDMARD treatment (p=0.028). The use of bDMARD had no significant effect on spinal fracture risk (OR=0.93, 95%-C.I.=0.85-1.01, p=0.09).

Conclusion

This study failed to demonstrate a beneficial effect on spinal fracture risk for AS patients treated with bDMARD during the last decade. Still bDMARD treatment delayed spinal fracture occurrence, which is promising with regard to results from future studies.

Trial registration

ClinicalTrials.gov, Identifier NCT02840695.

National Category
Orthopedics Rheumatology and Autoimmunity
Research subject
Orthopaedics
Identifiers
URN: urn:nbn:se:uu:diva-307365OAI: oai:DiVA.org:uu-307365DiVA: diva2:1046373
Available from: 2016-11-14 Created: 2016-11-14 Last updated: 2016-11-14
In thesis
1. Spinal fractures related to ankylosing spondylitis: Epidemiology, clinical outcome and biomechanics
Open this publication in new window or tab >>Spinal fractures related to ankylosing spondylitis: Epidemiology, clinical outcome and biomechanics
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Spinal fractures related to ankylosing spondylitis (AS) are often associated with serious complications. Therefore, knowledge of the incidence, best treatment, outcome, and prevention would assist in improving current guidelines.

Objectives: This thesis aims at (1) analysing the complications and mortality of surgical treatment, (2) mapping the incidence and treatment modalities for these patients in Sweden, as well as (3) investigating the putative preventive effect of biological disease modifying anti-rheumatic drug (bDMARD) therapy on spinal fractures related to AS.

Methods: Merged multiple national registries were used to identify predictors of mortality and spinal fractures in patients with AS. Beyond that a finite element model (FEM) was designed to simulating a cervicothoracic fracture related to AS.

Results and Conclusions: During the last two decades an increase of the incidence of vertebral fractures in patients with AS was observed. With the introduction of bDMARD treatment of AS was revolutionised and quality of life and function improved.  It seems that the improved quality of life and function in these patients does not correlate with a reduced fracture risk. Still, for the first time a beneficial effect of bDMARD with regard to spinal fracture occurrence was provided. The risk of spinal fractures was not reduced, but the debut of a spinal fracture was delayed with bDMARD. Since for this study the observation interval was only a decade, a future follow-up should revisit the effect of bDMARD on spinal fractures related to AS.

Furthermore, it was shown that posterior stabilisation is an effective method for restoring stability without the necessity of additional external fixation. Most likely the early rehabilitation reduced pulmonary complications, which in turn reduced early mortality of these fractures. The FEM could be used to identify the most appropriate implant configuration, since no well-established cadaver models exist.

Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT02840695.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 80 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1277
Keyword
ankylosing spondylitis, spinal fractures
National Category
Orthopedics
Research subject
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-307373 (URN)978-91-554-9751-4 (ISBN)
Public defence
2017-01-20, Gullstrandsalen, Akademiska sjukhuset, Ing 70, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2016-12-09 Created: 2016-11-14 Last updated: 2016-12-28

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