Do biological disease-modifying antirheumatic drugs reduce the spinal fracture risk related to ankylosing spondylitis? A longitudinal multiregistry matched cohort study

Yohan Robinson, Claes Olerud, Johan Willander, Yohan Robinson, Claes Olerud, Johan Willander

Abstract

Objectives: Ankylosing spondylitis (AS) is associated with an increased spinal fracture risk due to the loss of elasticity in spinal motion segments. With the introduction of biological disease-modifying antirheumatic drug (bDMARD) treatment for AS, the individual course of the disease has been ameliorated. This study aims to examine the association of bDMARD treatment and risk of spinal fracture.

Design: Longitudinal population-based multiregistry observational matched cohort study.

Setting: Swedish Patient Registry 1987-2014 and Swedish Prescribed Drugs Registry 2005-2014.

Participants: Included were patients ≥18 years of age receiving treatment at a healthcare facility for the primary diagnosis of AS. About 1352 patients received more than one prescription of bDMARD from 2005 to 2014. An untreated control group was created by propensity score matching for age, sex, comorbidity, antirheumatic prescriptions and years with AS (n=1352).

Main outcome measures: Spinal fracture-free survival.

Results: No bDMARD treatment-related effect on spinal fracture-free survival was observed in the matched cohorts. Male gender (HR=2.54, 95% CI 1.48 to 4.36) and Charlson Comorbidity Index score (HR=3.02, 95% CI 1.59 to 5.75) contributed significantly to spinal fracture risk.

Conclusion: bDMARD had no medium-term effect on the spinal fracture-free survival in patients with AS.

Trial registration number: NCT02840695; Post-results.

Keywords: ankylosing spondylitis; fracture; rheumatology; spine.

Conflict of interest statement

Competing interests: YR and CO have been paid for developing and delivering educational presentations for Medtronic and DePuy Synthes.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
CONSORT inclusion flow diagram. bDMARD, biological disease-modifying antirheumatic drugs; CONSORT, Consolidated Standards of Reporting Trials.
Figure 2
Figure 2
Adjusted survival curves of fracture-free years after first AS diagnosis in matched cohorts according to bDMARD treatment. AS, ankylosing spondylitis; bDMARD, biological disease-modifying antirheumatic drugs; CCI, Charlson Comorbidity Index.

References

    1. Boonen A, Brinkhuizen T, Landewé R, et al. . Impact of ankylosing spondylitis on sick leave, presenteeism and unpaid productivity, and estimation of the societal cost. Ann Rheum Dis 2010;69:1123–8. 10.1136/ard.2009.116764
    1. Haroon N, Danda D. ‘Bamboo spine’, a thing of the past? Int J Rheum Dis 2014;17:127–30. 10.1111/1756-185X.12326
    1. Muñoz-Ortego J, Vestergaard P, Rubio JB, et al. . Ankylosing spondylitis is associated with an increased risk of vertebral and nonvertebral clinical fractures: a population-based cohort study. J Bone Miner Res 2014;29:1770–6. 10.1002/jbmr.2217
    1. Baraliakos X, Sewerin P. Sport mit morbus bechterew? Warum? Und wenn ja: wie? Morbus-Bechterew Journal 2017;2017:18–20.
    1. Braun J, van den Berg R, Baraliakos X, et al. . 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2011;70:896–904. 10.1136/ard.2011.151027
    1. Maxwell LJ, Zochling J, Boonen A, et al. . TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database Syst Rev 2015;4:Cd005468.
    1. Prince DS, McGuigan LE, McGirr EE. Working life and physical activity in ankylosing spondylitis pre and post anti-tumor necrosis factor-alpha therapy. Int J Rheum Dis 2014;17:165–72. 10.1111/1756-185x.12018
    1. Baeten D, Sieper J, Braun J, et al. . Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med 2015;373:2534–48. 10.1056/NEJMoa1505066
    1. Braun J, Baraliakos X, Deodhar A, et al. . Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study. Ann Rheum Dis 2017;76:1070–7. 10.1136/annrheumdis-2016-209730
    1. Maas F, Arends S, Brouwer E, et al. . Reduction in spinal radiographic progression in ankylosing spondylitis patients receiving prolonged treatment with TNF-alpha inhibitors. Arthritis Care Res 2016. doi: 10.1002/acr.23097 [Epub ahead of print 4 Oct 2016].
    1. Haroon NN, Sriganthan J, Al Ghanim N, et al. . Effect of TNF-alpha inhibitor treatment on bone mineral density in patients with ankylosing spondylitis: a systematic review and meta-analysis. Semin Arthritis Rheum 2014;44:155–61. 10.1016/j.semarthrit.2014.05.008
    1. Briot K, Roux C. Inflammation, bone loss and fracture risk in spondyloarthritis. RMD Open 2015;1:e000052 10.1136/rmdopen-2015-000052
    1. Robinson Y, Willander J, Olerud C. Surgical stabilisation improves survival of spinal fractures related to ankylosing spondylitis. Spine 2016. [Epub ahead of print 11 Aug 2015].
    1. Benchimol EI, Smeeth L, Guttmann A, et al. . The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. PLoS Med 2015;12:e1001885 10.1371/journal.pmed.1001885
    1. von Elm E, Altman DG, Egger M, et al. . The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Int J Surg 2014;12:1495–9. 10.1016/j.ijsu.2014.07.013
    1. Ludvigsson JF, Andersson E, Ekbom A, et al. . External review and validation of the Swedish national inpatient register. BMC Public Health 2011;11:450 10.1186/1471-2458-11-450
    1. World Health Organisation. International statistical classification of diseases and related health problems. 2006.
    1. Socialstyrelsen. : Grafiska B, Classification of surgical procedures version 1.9. Revised version of 2004. Lindesberg, Sweden, 2004.
    1. Emilsson L, Lindahl B, Köster M, et al. . Review of 103 swedish healthcare quality registries. J Intern Med 2015;277:94–136. 10.1111/joim.12303
    1. Wettermark B, Hammar N, Fored CM, et al. . The new swedish prescribed drug register-opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf 2007;16:726–35. 10.1002/pds.1294
    1. Johansson LA, Westerling R. Comparing Swedish hospital discharge records with death certificates: implications for mortality statistics. Int J Epidemiol 2000;29:495–502. 10.1093/intjepid/29.3.495
    1. Sundararajan V, Henderson T, Perry C, et al. . New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol 2004;57:1288–94. 10.1016/j.jclinepi.2004.03.012
    1. R_Core_Team. R: a language and environment for statistical computing. Vienna, Austria, 2017.
    1. Moher D, Hopewell S, Schulz KF, et al. . CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:c869 10.1136/bmj.c869
    1. Vosse D, Landewé R, van der Heijde D, et al. . Ankylosing spondylitis and the risk of fracture: results from a large primary care-based nested case-control study. Ann Rheum Dis 2009;68:1839–42. 10.1136/ard.2008.100503
    1. Caron T, Bransford R, Nguyen Q, et al. . Spine fractures in patients with ankylosing spinal disorders. Spine 2010;35:E458–E464. 10.1097/BRS.0b013e3181cc764f
    1. Linder M, Byström C, Kieler H, et al. . Use of palivizumab is underestimated in the Swedish Prescribed Drug Register - implications for register-based drug studies. Clin Epidemiol 2015;7:45–51. 10.2147/CLEP.S73337
    1. Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc 2011;86:304–14. 10.4065/mcp.2010.0575
    1. Lee W, Reveille JD, Davis JC, et al. . Are there gender differences in severity of ankylosing spondylitis? Results from the PSOAS cohort. Ann Rheum Dis 2007;66:633–8. 10.1136/ard.2006.060293
    1. Robinson Y, Sandén B, Olerud C. Increased occurrence of spinal fractures related to ankylosing spondylitis: a prospective 22-year cohort study in 17,764 patients from a national registry in Sweden. Patient Saf Surg 2013;7:2 10.1186/1754-9493-7-2
    1. Kalkan A, Husberg M, Hallert E, et al. . Physician preferences and variations in prescription of biologic drugs for rheumatoid arthritis: A register-based study of 4,010 patients in Sweden. Arthritis Care Res 2015;67:1679–85. 10.1002/acr.22640
    1. Robinson Y, Robinson AL, Olerud C. Complications and survival after long posterior instrumentation of cervical and cervicothoracic fractures related to ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis. Spine 2015;40:E227–E233. 10.1097/BRS.0000000000000726
    1. Carter S, Lories RJ. Osteoporosis: a paradox in ankylosing spondylitis. Curr Osteoporos Rep 2011;9:112–5. 10.1007/s11914-011-0058-z
    1. Maas F, Spoorenberg A, Brouwer E, et al. . Radiographic vertebral fractures develop in patients with ankylosing spondylitis during 4 years of TNF-α blocking therapy. Clin Exp Rheumatol 2016;34:191–9.
    1. Millner JR, Barron JS, Beinke KM, et al. . Exercise for ankylosing spondylitis: An evidence-based consensus statement. Semin Arthritis Rheum 2016;45:411–27. 10.1016/j.semarthrit.2015.08.003

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