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Should axial spondyloarthritis without radiographic changes be treated with anti-TNF agents?

  • Therapy Review
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Abstract

A spectrum of disease extends beyond the rigid confines of ankylosing spondylitis (AS). Axial spondyloarthritis (axSpA) encompasses non-radiographic axSpA (nr-axSpA) in individuals without established radiographic changes but with other clinical/imaging axSpA features and AS in those with definite sacroiliac joint changes on pelvic X-rays. A broad consensus about the management of nr-axSpA is emerging among clinicians, but the evidence base remains open to question. To explore whether nr-axSpA and AS should be treated similarly, we examined the literature on their prevalence, natural history, disease burden, and treatment. There is strong evidence that nr-axSpA and AS are expressions of the same disease. Approximately 10% of patients with nr-axSpA will develop radiographic disease over 2 years; after >20 years, the figure may exceed 80%. Nr-axSpA patients have lower CRP and less spinal inflammation on MRI than AS patients but similar disease activity, pain, and quality-of-life impairment. Most patients with nr-axSpA manage well with conservative treatment, but a minority has severe disabling symptoms. Anti-TNF therapy has demonstrated similar efficacy and safety in nr-axSpA and AS. Current evidence does not clearly indicate that anti-TNF treatment can inhibit or limit bony progression of AS, the basis of conservative and anti-TNF treatment is control of symptoms and function. For some patients with nr-axSpA, the need for powerful treatments is as great as in some with AS; thus, treatment of axSpA should be consistent across the axSpA spectrum with anti-TNF agents being available, irrespective of radiographic change, according to the same criteria as those applied to AS.

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References

  1. Boonen A, Braun J, van der Horst Bruinsma IE, Huang F, Maksymowych W, Kostanjsek N, Cieza A, Stucki G, van der Heijde D (2010) ASAS/WHO ICF Core Sets for ankylosing spondylitis (AS): how to classify the impact of AS on functioning and health. Ann Rheum Dis 69(1):102–107. doi:10.1136/ard.2008.104117

    Article  CAS  PubMed  Google Scholar 

  2. Zink A, Braun J, Listing J, Wollenhaupt J (2000) Disability and handicap in rheumatoid arthritis and ankylosing spondylitis–results from the German rheumatological database. German Collaborative Arthritis Centers. J Rheumatol 27(3):613–622

    CAS  PubMed  Google Scholar 

  3. Rudwaleit M, van der Heijde D, Landewe R, Listing J, Akkoc N, Brandt J, Braun J, Chou CT, Collantes-Estevez E, Dougados M, Huang F, Gu J, Khan MA, Kirazli Y, Maksymowych WP, Mielants H, Sorensen IJ, Ozgocmen S, Roussou E, Valle-Onate R, Weber U, Wei J, Sieper J (2009) The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 68(6):777–783. doi:10.1136/ard.2009.108233

    Article  CAS  PubMed  Google Scholar 

  4. Rudwaleit M, Landewe R, van der Heijde D, Listing J, Brandt J, Braun J, Burgos-Vargas R, Collantes-Estevez E, Davis J, Dijkmans B, Dougados M, Emery P, van der Horst-Bruinsma IE, Inman R, Khan MA, Leirisalo-Repo M, van der Linden S, Maksymowych WP, Mielants H, Olivieri I, Sturrock R, de Vlam K, Sieper J (2009) The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis 68(6):770–776. doi:10.1136/ard.2009.108217

    Article  CAS  PubMed  Google Scholar 

  5. Isdale A, Keat A, Barkham N, Bennett AN, Gaffney K, Marzo-Ortega H, Sengupta R (2013) Expanding the spectrum of inflammatory spinal disease: aS it was, as it is now. Rheumatology (Oxford) 52(12):2103–2105. doi:10.1093/rheumatology/ket244

    Article  Google Scholar 

  6. Jones A, Harrison N, Jones T, Rees JD, Bennett AN (2014) Time to diagnosis of axial spondylarthritis in clinical practice: signs of improving awareness? Rheumatology (Oxford) 53(11):2126–2127. doi:10.1093/rheumatology/keu294

    Article  Google Scholar 

  7. Sykes M, Doll H, Sengupta R, Gaffney K (2014) Delay to diagnosis in axial spondyloarthritis: are we improving? Rheumatology (Oxford) 53(suppl1):i143

    Article  Google Scholar 

  8. Hamilton L, Gilbert A, Skerrett J, Dickinson S, Gaffney K (2011) Services for people with ankylosing spondylitis in the UK—a survey of rheumatologists and patients. Rheumatology (Oxford) 50(11):1991–1998. doi:10.1093/rheumatology/ker013

    Article  Google Scholar 

  9. Aloush V, Ablin JN, Reitblat T, Caspi D, Elkayam O (2007) Fibromyalgia in women with ankylosing spondylitis. Rheumatol Int 27(9):865–868. doi:10.1007/s00296-007-0344-3

    Article  PubMed  Google Scholar 

  10. van der Heijde D, Salonen D, Weissman BN, Landewe R, Maksymowych WP, Kupper H, Ballal S, Gibson E, Wong R (2009) Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther 11(4):R127. doi:10.1186/ar2794

    Article  PubMed  PubMed Central  Google Scholar 

  11. van der Heijde D, Landewe R, Einstein S, Ory P, Vosse D, Ni L, Lin SL, Tsuji W, Davis JC Jr (2008) Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 58(5):1324–1331. doi:10.1002/art.23471

    Article  PubMed  Google Scholar 

  12. van der Heijde D, Landewe R, Baraliakos X, Houben H, van Tubergen A, Williamson P, Xu W, Baker D, Goldstein N, Braun J (2008) Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum 58(10):3063–3070. doi:10.1002/art.23901

    Article  PubMed  Google Scholar 

  13. Baraliakos X, Haibel H, Listing J, Sieper J, Braun J (2014) Continuous long-term anti-TNF therapy does not lead to an increase in the rate of new bone formation over 8 years in patients with ankylosing spondylitis. Ann Rheum Dis 73(4):710–715. doi:10.1136/annrheumdis-2012-202698

    Article  CAS  PubMed  Google Scholar 

  14. Bennett AN, McGonagle D, O’Connor P, Hensor EM, Sivera F, Coates LC, Emery P, Marzo-Ortega H (2008) Severity of baseline magnetic resonance imaging-evident sacroiliitis and HLA-B27 status in early inflammatory back pain predict radiographically evident ankylosing spondylitis at 8 years. Arthritis Rheum 58(11):3413–3418. doi:10.1002/art.24024

    Article  CAS  PubMed  Google Scholar 

  15. Sampaio-Barros PD, Bortoluzzo AB, Conde RA, Costallat LT, Samara AM, Bertolo MB (2010) Undifferentiated spondyloarthritis: a longterm followup. J Rheumatol 37(6):1195–1199. doi:10.3899/jrheum.090625

    Article  PubMed  Google Scholar 

  16. Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Marker-Hermann E, Zeidler H, Braun J, Sieper J (2011) Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis. Ann Rheum Dis 70(8):1369–1374. doi:10.1136/ard.2010.145995

    Article  PubMed  Google Scholar 

  17. Baraliakos X, Listing J, von der Recke A, Braun J (2009) The natural course of radiographic progression in ankylosing spondylitis–evidence for major individual variations in a large proportion of patients. J Rheumatol 36(5):997–1002. doi:10.3899/jrheum.080871

    Article  PubMed  Google Scholar 

  18. Cinar FI, Cinar M, Yilmaz S, Simsek I, Erdem H, Pay S (2014) Thoughts and perceptions of ankylosing spondylitis patients with regard to TNF inhibitors. Rheumatol Int 34(7):979–986. doi:10.1007/s00296-013-2931-9

    Article  CAS  PubMed  Google Scholar 

  19. Stockdale J, Goodacre L (2009) ‘It’s magic stuff’: the experiences of patients with ankylosing spondylitis taking anti-TNF-alpha medication. Musculoskeletal Care 7(3):162–177. doi:10.1002/msc.146

    Article  CAS  PubMed  Google Scholar 

  20. Braun J, Pham T, Sieper J, Davis J, van der Linden S, Dougados M, van der Heijde D (2003) International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis 62(9):817–824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zochling J, van der Heijde D, Burgos-Vargas R, Collantes E, Davis JC Jr, Dijkmans B, Dougados M, Geher P, Inman RD, Khan MA, Kvien TK, Leirisalo-Repo M, Olivieri I, Pavelka K, Sieper J, Stucki G, Sturrock RD, van der Linden S, Wendling D, Bohm H, van Royen BJ, Braun J (2006) ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 65(4):442–452. doi:10.1136/ard.2005.041137

    Article  CAS  PubMed  Google Scholar 

  22. Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, Dagfinrud H, Dijkmans B, Dougados M, Emery P, Geher P, Hammoudeh M, Inman RD, Jongkees M, Khan MA, Kiltz U, Kvien T, Leirisalo-Repo M, Maksymowych WP, Olivieri I, Pavelka K, Sieper J, Stanislawska-Biernat E, Wendling D, Ozgocmen S, van Drogen C, van Royen B, van der Heijde D (2011) 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 70(6):896–904. doi:10.1136/ard.2011.151027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. van der Heijde D, Sieper J, Maksymowych WP, Dougados M, Burgos-Vargas R, Landewe R, Rudwaleit M, Braun J (2011) 2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis. Ann Rheum Dis 70(6):905–908. doi:10.1136/ard.2011.151563

    Article  PubMed  Google Scholar 

  24. Ward MM, Deodhar A, Akl EA, Lui A, Ermann J, Gensler LS, Smith JA, Borenstein D, Hiratzka J, Weiss PF, Inman RD, Majithia V, Haroon N, Maksymowych WP, Joyce J, Clark BM, Colbert RA, Figgie MP, Hallegua DS, Prete PE, Rosenbaum JT, Stebulis JA, van den Bosch F, Yu DT, Miller AS, Reveille JD, Caplan L (2016) American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol 68(2):282–298. doi:10.1002/art.39298

    Article  PubMed  Google Scholar 

  25. National Institute for Health and Clinical Excellence (NICE) (2016) Technology appraisal TA383: TNF alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis

  26. van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27(4):361–368

    Article  PubMed  Google Scholar 

  27. Hamilton L, Macgregor A, Toms A, Warmington V, Pinch E, Gaffney K (2014) The prevalence of axial spondyloarthropathy in the UK: a cross sectional cohort study in a primary care population. Rheumatology (Oxford) 53(suppl 1):i30–i31

    Article  Google Scholar 

  28. van Hoeven L, Luime J, Han H, Vergouwe Y, Weel A (2014) Identifying axial spondyloarthritis in dutch primary care patients, ages 20–45 years, with chronic low back pain. Arthritis Care Res 66(3):446–453. doi:10.1002/acr.22180

    Article  Google Scholar 

  29. Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ (2014) Global prevalence of ankylosing spondylitis. Rheumatology (Oxford) 53(4):650–657. doi:10.1093/rheumatology/ket387

    Article  Google Scholar 

  30. Said-Nahal R, Miceli-Richard C, Berthelot JM, Duche A, Dernis-Labous E, Le Blevec G, Saraux A, Perdriger A, Guis S, Claudepierre P, Sibilia J, Amor B, Dougados M, Breban M (2000) The familial form of spondylarthropathy: a clinical study of 115 multiplex families. Groupe Francais d’Etude Genetique des Spondylarthropathies. Arthritis Rheum 43(6):1356–1365. doi:10.1002/1529-0131(200006)43:6<1356:AID-ANR20>3.0.CO;2-Y

    Article  CAS  PubMed  Google Scholar 

  31. Poddubnyy D, Brandt H, Vahldiek J, Spiller I, Song IH, Rudwaleit M, Sieper J (2012) The frequency of non-radiographic axial spondyloarthritis in relation to symptom duration in patients referred because of chronic back pain: results from the Berlin early spondyloarthritis clinic. Ann Rheum Dis 71(12):1998–2001. doi:10.1136/annrheumdis-2012-201945

    Article  PubMed  Google Scholar 

  32. Sampaio-Barros PD, Bertolo MB, Kraemer MH, Marques-Neto JF, Samara AM (2001) Undifferentiated spondyloarthropathies: a 2-year follow-up study. Clin Rheumatol 20(3):201–206

    Article  CAS  PubMed  Google Scholar 

  33. Costantino F, Zeboulon-Ktorza N, Said-Nahal R, D’Agostino MA, Breban M (2014) Factors associated with radiographic sacroiliitis in spondyloarthritis (SpA): results from cross-sectional and longitudinal analyses in a cohort of multiples families. Ann Rheum Dis 73(Suppl2):423

    Google Scholar 

  34. Huerta-Sil G, Casasola-Vargas JC, Londono JD, Rivas-Ruiz R, Chavez J, Pacheco-Tena C, Cardiel MH, Vargas-Alarcon G, Burgos-Vargas R (2006) Low grade radiographic sacroiliitis as prognostic factor in patients with undifferentiated spondyloarthritis fulfilling diagnostic criteria for ankylosing spondylitis throughout follow up. Ann Rheum Dis 65(5):642–646. doi:10.1136/ard.2005.043471

    Article  CAS  PubMed  Google Scholar 

  35. Chung HY, Machado P, van der Heijde D, D’Agostino MA, Dougados M (2012) Smokers in early axial spondyloarthritis have earlier disease onset, more disease activity, inflammation and damage, and poorer function and health-related quality of life: results from the DESIR cohort. Ann Rheum Dis 71(6):809–816. doi:10.1136/annrheumdis-2011-200180

    Article  PubMed  Google Scholar 

  36. Poddubnyy D, Haibel H, Listing J, Marker-Hermann E, Zeidler H, Braun J, Sieper J, Rudwaleit M (2012) Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis. Arthritis Rheum 64(5):1388–1398. doi:10.1002/art.33465

    Article  PubMed  Google Scholar 

  37. Boonen A, van der Linden SM (2006) The burden of ankylosing spondylitis. J Rheumatol Suppl 78:4–11

    PubMed  Google Scholar 

  38. Kiltz U, van der Heijde D (2009) Health-related quality of life in patients with rheumatoid arthritis and in patients with ankylosing spondylitis. Clin Exp Rheumatol 27(4 Suppl 55):S108–S111

    CAS  PubMed  Google Scholar 

  39. Jacobs P, Bissonnette R, Guenther LC (2011) Socioeconomic burden of immune-mediated inflammatory diseases: focusing on work productivity and disability. J Rheumatol Suppl 88:55–61. doi:10.3899/jrheum.110901

    Article  PubMed  Google Scholar 

  40. Davis JC, van der Heijde D, Dougados M, Woolley JM (2005) Reductions in health-related quality of life in patients with ankylosing spondylitis and improvements with etanercept therapy. Arthritis Rheum 53(4):494–501. doi:10.1002/art.21330

    Article  PubMed  Google Scholar 

  41. Ariza-Ariza R, Hernandez-Cruz B, Navarro-Sarabia F (2003) Physical function and health-related quality of life of Spanish patients with ankylosing spondylitis. Arthritis Rheum 49(4):483–487. doi:10.1002/art.11197

    Article  PubMed  Google Scholar 

  42. Khan MA, Khan MK, Kushner I (1981) Survival among patients with ankylosing spondylitis: a life-table analysis. J Rheumatol 8(1):86–90

    CAS  PubMed  Google Scholar 

  43. Radford EP, Doll R, Smith PG (1977) Mortality among patients with ankylosing spondylitis not given X-ray therapy. N Engl J Med 297(11):572–576. doi:10.1056/NEJM197709152971103

    Article  CAS  PubMed  Google Scholar 

  44. Lehtinen K (1993) Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis. Ann Rheum Dis 52(3):174–176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ciurea A, Scherer A, Exer P, Bernhard J, Dudler J, Beyeler B, Kissling R, Stekhoven D, Rufibach K, Tamborrini G, Weiss B, Muller R, Nissen MJ, Michel BA, van der Heijde D, Dougados M, Boonen A, Weber U (2013) Tumor necrosis factor alpha inhibition in radiographic and nonradiographic axial spondyloarthritis: results from a large observational cohort. Arthritis Rheum 65(12):3096–3106. doi:10.1002/art.38140

    Article  CAS  PubMed  Google Scholar 

  46. Dougados M, d’Agostino MA, Benessiano J, Berenbaum F, Breban M, Claudepierre P, Combe B, Dargent-Molina P, Daures JP, Fautrel B, Feydy A, Goupille P, Leblanc V, Logeart I, Pham T, Richette P, Roux C, Rudwaleit M, Saraux A, Treluyer JM, van der Heijde D, Wendling D (2011) The DESIR cohort: a 10-year follow-up of early inflammatory back pain in France: study design and baseline characteristics of the 708 recruited patients. Joint Bone Spine 78(6):598–603. doi:10.1016/j.jbspin.2011.01.013

    Article  PubMed  Google Scholar 

  47. Althoff CE, Sieper J, Song IH, Haibel H, Weiss A, Diekhoff T, Rudwaleit M, Freundlich B, Hamm B, Hermann KG (2013) Active inflammation and structural change in early active axial spondyloarthritis as detected by whole-body MRI. Ann Rheum Dis 72(6):967–973. doi:10.1136/annrheumdis-2012-201545

    Article  PubMed  Google Scholar 

  48. Rudwaleit M, Haibel H, Baraliakos X, Listing J, Marker-Hermann E, Zeidler H, Braun J, Sieper J (2009) The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum 60(3):717–727. doi:10.1002/art.24483

    Article  CAS  PubMed  Google Scholar 

  49. Kiltz U, Baraliakos X, Karakostas P, Igelmann M, Kalthoff L, Klink C, Krause D, Schmitz-Bortz E, Florecke M, Bollow M, Braun J (2012) Do patients with non-radiographic axial spondylarthritis differ from patients with ankylosing spondylitis? Arthritis Care Res 64(9):1415–1422. doi:10.1002/acr.21688

    Article  Google Scholar 

  50. Kiltz U, Baraliakos X, Karakostas P, Igelmann M, Kalthoff L, Klink C, Krause D, Schmitz-Bortz E, Florecke M, Bollow M, Braun J (2012) The degree of spinal inflammation is similar in patients with axial spondyloarthritis who report high or low levels of disease activity: a cohort study. Ann Rheum Dis 71(7):1207–1211. doi:10.1136/annrheumdis-2011-200508

    Article  CAS  PubMed  Google Scholar 

  51. Landewe R, Braun J, Deodhar A, Dougados M, Maksymowych WP, Mease PJ, Reveille JD, Rudwaleit M, van der Heijde D, Stach C, Hoepken B, Fichtner A, Coteur G, de Longueville M, Sieper J (2014) Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study. Ann Rheum Dis 73(1):39–47. doi:10.1136/annrheumdis-2013-204231

    Article  CAS  PubMed  Google Scholar 

  52. Husain M, Brophy S, Cooksey R, Rahman MA, Pillips CJ, Siebert S (2014) The cost of ankylosing spondylitis to the UK NHS. Rheumatology (Oxford) 53(suppl1):i138

    Article  Google Scholar 

  53. Reveille JD, Ximenes A, Ward MM (2012) Economic considerations of the treatment of ankylosing spondylitis. Am J Med Sci 343(5):371–374. doi:10.1097/MAJ.0b013e3182514093

    Article  PubMed  PubMed Central  Google Scholar 

  54. Rafia R, Ara R, Packham J, Haywood KL, Healey E (2012) Healthcare costs and productivity losses directly attributable to ankylosing spondylitis. Clin Exp Rheumatol 30(2):246–253

    PubMed  Google Scholar 

  55. Healey EL, Haywood KL, Jordan KP, Garratt A, Packham JC (2011) Impact of ankylosing spondylitis on work in patients across the UK. Scand J Rheumatol 40(1):34–40. doi:10.3109/03009742.2010.487838

    Article  CAS  PubMed  Google Scholar 

  56. Husain MJ, Brophy S, Cooksey R, Rahman MA, Phillips CJ, Siebert S (2014) The work-related costs of ankylosing spondylitis in a UK cohort. Rheumatology (Oxford) 53(suppl 1):i140–141

    Article  Google Scholar 

  57. Dean LE, MacDonald AG, Sturrock RD, Hunter J, Marshall D, Macfarlane GJ, Jones GT (2014) The impact of ankylosing spondylitis on work impairment: data from the Scotland Registry for ankylosing spondylitis. Arthritis Rheumatol 66(suppl):S17

    Google Scholar 

  58. Boonen A, Brinkhuizen T, Landewe R, van der Heijde D, Severens JL (2010) Impact of ankylosing spondylitis on sick leave, presenteeism and unpaid productivity, and estimation of the societal cost. Ann Rheum Dis 69(6):1123–1128. doi:10.1136/ard.2009.116764

    Article  PubMed  Google Scholar 

  59. Verstappen SM, Watson KD, Lunt M, McGrother K, Symmons DP, Hyrich KL (2010) Working status in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford) 49(8):1570–1577. doi:10.1093/rheumatology/keq131

    Article  Google Scholar 

  60. van der Heijde D, Braun J, Rudwaleit M et al (2013) Improvements in work and household productivity after 24 weeks of certolizumab pegol in treatment of axial spondyloarthritis patients, including patients with ankylosing spondylitis: results of RAPID-AXSPA Study. Ann Rheum Dis 72(Suppl3):87

    Google Scholar 

  61. van der Heijde D, Joshi A, Mittal M, Pangan A, Chen N, Betts K, Qi C, Bao Y (2014) ASAS40 and ASDAS responses are associated with improved physical function, HRQOL, and work productivity in patients with non-radiographic axial spondyloarthritis. Ann Rheum Dis 73(suppl2):715

    Google Scholar 

  62. Reilly MC, Gooch KL, Wong RL, Kupper H, van der Heijde D (2010) Validity, reliability and responsiveness of the work productivity and activity impairment questionnaire in ankylosing spondylitis. Rheumatology (Oxford) 49(4):812–819. doi:10.1093/rheumatology/kep457

    Article  Google Scholar 

  63. Dougados M, Tsai WC, Saaibi DL, Bonin R, Bukowski J, Pedersen R, Vlahos B, Kotak S (2015) Evaluation of health outcomes with etanercept treatment in patients with early nonradiographic axial spondyloarthritis. J Rheumatol. doi:10.3899/jrheum.141313

    Google Scholar 

  64. van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J, Dougados M, Reveille JD, Wong RL, Kupper H, Davis JC Jr (2006) Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 54(7):2136–2146. doi:10.1002/art.21913

    Article  PubMed  Google Scholar 

  65. Lambert RG, Salonen D, Rahman P, Inman RD, Wong RL, Einstein SG, Thomson GT, Beaulieu A, Choquette D, Maksymowych WP (2007) Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 56(12):4005–4014. doi:10.1002/art.23044

    Article  CAS  PubMed  Google Scholar 

  66. Gorman JD, Sack KE, Davis JC Jr (2002) Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med 346(18):1349–1356. doi:10.1056/NEJMoa012664

    Article  CAS  PubMed  Google Scholar 

  67. Davis JC Jr, Van Der Heijde D, Braun J, Dougados M, Cush J, Clegg DO, Kivitz A, Fleischmann R, Inman R, Tsuji W (2003) Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum 48(11):3230–3236. doi:10.1002/art.11325

    Article  CAS  PubMed  Google Scholar 

  68. Calin A, Dijkmans BA, Emery P, Hakala M, Kalden J, Leirisalo-Repo M, Mola EM, Salvarani C, Sanmarti R, Sany J, Sibilia J, Sieper J, van der Linden S, Veys E, Appel AM, Fatenejad S (2004) Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis. Ann Rheum Dis 63(12):1594–1600. doi:10.1136/ard.2004.020875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. van der Heijde D, Da Silva JC, Dougados M, Geher P, van der Horst-Bruinsma I, Juanola X, Olivieri I, Raeman F, Settas L, Sieper J, Szechinski J, Walker D, Boussuge MP, Wajdula JS, Paolozzi L, Fatenejad S (2006) Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis. Ann Rheum Dis 65(12):1572–1577. doi:10.1136/ard.2006.056747

    Article  PubMed  PubMed Central  Google Scholar 

  70. Dougados M, Braun J, Szanto S, Combe B, Elbaz M, Geher P, Thabut G, Leblanc V, Logeart I (2011) Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomised double-blind placebo-controlled study (SPINE). Ann Rheum Dis 70(5):799–804. doi:10.1136/ard.2010.139261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, Mack M, Han J, Visvanathan S, Xu Z, Hsu B, Beutler A, Braun J (2008) Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum 58(11):3402–3412. doi:10.1002/art.23969

    Article  CAS  PubMed  Google Scholar 

  72. Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, Gromnica-Ihle E, Kellner H, Krause A, Schneider M, Sorensen H, Zeidler H, Thriene W, Sieper J (2002) Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 359(9313):1187–1193

    Article  CAS  PubMed  Google Scholar 

  73. Van Den Bosch F, Kruithof E, Baeten D, Herssens A, de Keyser F, Mielants H, Veys EM (2002) Randomized double-blind comparison of chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab) versus placebo in active spondylarthropathy. Arthritis Rheum 46(3):755–765. doi:10.1002/art.511

    Article  Google Scholar 

  74. Marzo-Ortega H, McGonagle D, Jarrett S, Haugeberg G, Hensor E, O’Connor P, Tan AL, Conaghan PG, Greenstein A, Emery P (2005) Infliximab in combination with methotrexate in active ankylosing spondylitis: a clinical and imaging study. Ann Rheum Dis 64(11):1568–1575. doi:10.1136/ard.2004.022582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. van der Heijde D, Dijkmans B, Geusens P, Sieper J, DeWoody K, Williamson P, Braun J (2005) Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 52(2):582–591. doi:10.1002/art.20852

    Article  PubMed  Google Scholar 

  76. Dougados M, van der Heijde D, Sieper J, Braun J, Maksymowych WP, Citera G, Miceli-Richard C, Wei JC, Pedersen R, Bonin R, Rahman MU, Logeart I, Wajdula J, Koenig AS, Vlahos B, Alvarez D, Bukowski JF (2014) Symptomatic efficacy of etanercept and its effects on objective signs of inflammation in early nonradiographic axial spondyloarthritis: a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol 66(8):2091–2102. doi:10.1002/art.38721

    Article  CAS  PubMed  Google Scholar 

  77. Sieper J, van der Heijde D, Dougados M, Mease PJ, Maksymowych WP, Brown MA, Arora V, Pangan AL (2013) Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis 72(6):815–822. doi:10.1136/annrheumdis-2012-201766

    Article  CAS  PubMed  Google Scholar 

  78. van der Heijde D, Joshi A, Pangan AL, Chen N, Betts K, Mittal M, Bao Y (2015) ASAS40 and ASDAS clinical responses in the ABILITY-1 clinical trial translate to meaningful improvements in physical function, health-related quality of life and work productivity in patients with non-radiographic axial spondyloarthritis. Rheumatology (Oxford). doi:10.1093/rheumatology/kev267

    Google Scholar 

  79. National Institute for Health and Clinical Excellence (NICE) (2008) Technology Appraisal TA143: Ankylosing spondylitis—adalimumab, etanercept and infliximab, 25 June 2015

  80. National Institute for Health and Clinical Excellence (NICE) (2011) Technology appraisal TA233: ankylosing spondylitis—golimumab. NICE. http://guidance.nice.org.uk/TA233. Accessed 1 July 2015

  81. Song IH, Weiss A, Hermann KG, Haibel H, Althoff CE, Poddubnyy D, Listing J, Lange E, Freundlich B, Rudwaleit M, Sieper J (2013) Similar response rates in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis after 1 year of treatment with etanercept: results from the ESTHER trial. Ann Rheum Dis 72(6):823–825. doi:10.1136/annrheumdis-2012-202389

    Article  CAS  PubMed  Google Scholar 

  82. Callhoff J, Sieper J, Weiss A, Zink A, Listing J (2015) Efficacy of TNFalpha blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis. Ann Rheum Dis 74(6):1241–1248. doi:10.1136/annrheumdis-2014-205322

    Article  CAS  PubMed  Google Scholar 

  83. Haroon N, Inman RD, Learch TJ, Weisman MH, Lee M, Rahbar MH, Ward MM, Reveille JD, Gensler LS (2013) The impact of tumor necrosis factor alpha inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum 65(10):2645–2654. doi:10.1002/art.38070

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Zavada J, Uher M, Sisol K, Forejtova S, Jarosova K, Mann H, Vencovsky J, Pavelka K (2016) A tailored approach to reduce dose of anti-TNF drugs may be equally effective, but substantially less costly than standard dosing in patients with ankylosing spondylitis over 1 year: a propensity score-matched cohort study. Ann Rheum Dis 75(1):96–102. doi:10.1136/annrheumdis-2014-205202

    Article  PubMed  Google Scholar 

  85. Fong W, Holroyd C, Davidson B, Armstrong R, Harvey N, Dennison E, Cooper C, Edwards CJ (2016) The effectiveness of a real life dose reduction strategy for tumour necrosis factor inhibitors in ankylosing spondylitis and psoriatic arthritis. Rheumatology (Oxford) 55(10):1837–1842. doi:10.1093/rheumatology/kew269

    Article  Google Scholar 

  86. Braun J, van der Horst-Bruinsma IE, Huang F, Burgos-Vargas R, Vlahos B, Koenig AS, Freundlich B (2011) Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis: a randomized, double-blind trial. Arthritis Rheum 63(6):1543–1551. doi:10.1002/art.30223

    Article  CAS  PubMed  Google Scholar 

  87. Chen J, Lin S, Liu C (2014) Sulfasalazine for ankylosing spondylitis. Cochrane Database Syst Rev 11:004800. doi:10.1002/14651858.CD004800.pub3

    Google Scholar 

  88. Lie E, Kristensen LE, Forsblad-d’Elia H, Zverkova-Sandstrom T, Askling J, Jacobsson LT, Group AS (2015) The effect of comedication with conventional synthetic disease modifying antirheumatic drugs on TNF inhibitor drug survival in patients with ankylosing spondylitis and undifferentiated spondyloarthritis: results from a nationwide prospective study. Ann Rheum Dis 74(6):970–978. doi:10.1136/annrheumdis-2014-206616

    Article  CAS  PubMed  Google Scholar 

  89. Heinonen AV, Aaltonen KJ, Joensuu JT, Lahteenmaki JP, Pertovaara MI, Romu MK, Hirvonen HE, Simila AK, Blom ML, Nordstrom DC (2015) Effectiveness and drug survival of TNF inhibitors in the treatment of ankylosing spondylitis: a prospective cohort study. J Rheumatol 42(12):2339–2346. doi:10.3899/jrheum.150389

    Article  CAS  PubMed  Google Scholar 

  90. Wu LC, Leong PY, Yeo KJ, Li TY, Wang YH, Chiou JY, Wei JC (2016) Celecoxib and sulfasalazine had negative association with coronary artery diseases in patients with ankylosing spondylitis: a nation-wide, population-based case-control study. Medicine 95(36):e4792. doi:10.1097/MD.0000000000004792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Dougados M, van der Heijde D, Sieper J et al (2013) Clinical and imaging efficacy of etanercept in early non-radiographic axial spondyloarthritis: a 12-week, randomized, double-blind, placebo-controlled trial. Ann Rheum Dis 72(Suppl):87

    Google Scholar 

  92. Sieper J, Lenaerts J, Wollenhaupt J, Rudwaleit M, Mazurov VI, Myasoutova L, Park S, Song Y, Yao R, Chitkara D, Vastesaeger N (2014) Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1. Ann Rheum Dis 73(1):101–107. doi:10.1136/annrheumdis-2012-203201

    Article  CAS  PubMed  Google Scholar 

  93. Breban M, Ravaud P, Claudepierre P, Baron G, Henry YD, Hudry C, Euller-Ziegler L, Pham T, Solau-Gervais E, Chary-Valckenaere I, Marcelli C, Perdriger A, Le Loet X, Wendling D, Fautrel B, Fournie B, Combe B, Gaudin P, Jousse S, Mariette X, Baleydier A, Trape G, Dougados M (2008) Maintenance of infliximab treatment in ankylosing spondylitis: results of a 1-year randomized controlled trial comparing systematic versus on-demand treatment. Arthritis Rheum 58(1):88–97. doi:10.1002/art.23167

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

We are grateful to Dr. Stefan Siebert for helpful comments on the manuscript. Editorial/medical writing support was provided by Donna McGuire of Engage Scientific Solutions and was funded by Pfizer Inc.

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This work was supported by Pfizer.

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Authors and Affiliations

  1. Rheumatology Department, Arthritis Centre, Northwick Park Hospital, Harrow, Middlesex, HA1 3UJ, UK

    Andrew Keat

  2. NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust and Leeds Institute of Rheumatic and Musculoskeletal Disease, University of Leeds, Leeds, UK

    Alexander N. Bennett & Helena Marzo-Ortega

  3. Academic Department of Military Rehabilitation, Defence Medical Rehabilitation Centre, Headley Court, Epsom, Surrey, UK

    Alexander N. Bennett

  4. Rheumatology Department, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, Norfolk, UK

    Karl Gaffney

  5. Royal National Hospital for Rheumatic Diseases, Bath, UK

    Raj Sengupta

  6. Pfizer Ltd, Tadworth, Surrey, UK

    Tamara Everiss

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  1. Andrew Keat
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  2. Alexander N. Bennett
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Correspondence to Andrew Keat.

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Conflict of interest

AK has received research funding from Abbvie and Pfizer and payments for speaking, chairing and attending ad hoc advisory boards from Abbvie, MSD, Biogen, Novartis, Pfizer, and UCB; ANB has received advisory board fees from Abbvie Ltd, MSD, Novartis, Pfizer, and UCB, research grants from Pfizer, and teaching honoraria from Abbvie Ltd, Pfizer, and UCB; KG has received speaker fees, consultancy fees, educational grants, and research funding from Abbvie, Pfizer, MSD, Napp, Novartis, and UCB; HMO has received grants and/or honoraria from Abbvie, Celgene, Jannsen, MSD, Novartis, Pfizer, and UCB; RS has received advisory board fees from Abbvie, MSD, Novartis, Pfizer, and UCB, research grants from Pfizer, and teaching honoraria from Abbvie, Pfizer, and UCB; TE is a Pfizer employee and owns stock options from Pfizer.

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Keat, A., Bennett, A.N., Gaffney, K. et al. Should axial spondyloarthritis without radiographic changes be treated with anti-TNF agents?. Rheumatol Int 37, 327–336 (2017). https://doi.org/10.1007/s00296-016-3635-8

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