Current Treatment Options in Rheumatology

, Volume 4, Issue 2, pp 158–173 | Cite as

Personalized Axial Spondyloarthritis Care

  • Nurullah Akkoc
Seronegative Arthritis (N Haroon, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Seronegative Arthritis


Purpose of review

To discuss the personalized care of patients with axial spondyloarthritis.

Recent findings

Secukinumab, an IL-17A inhibitor, has recently been proven to be effective in treating signs and symptoms of ankylosing spondylitis. The latest update of ASAS/EULAR management recommendations include secukinumab and recommend a personalized medicine approach for the treatment of patients with axial spondyloarthritis.


Nonsteroidal anti-inflammatory drugs benefit a significant proportion of patients with axial spondyloarthritis. Conventional disease-modifying anti-rheumatic drugs are not effective for axial symptoms. Sulfasalazine may have limited efficacy for peripheral articular symptoms, but not for enthesitis. Local glucocorticoid injections may be helpful for joint and entheseal inflammation. Patients failing to respond to conventional treatments can be treated with biologics inhibiting TNF-α and IL-17A. They all have a similar efficacy for the treatment of axial and peripheral disease but vary in their efficacy on the extra-articular disease manifestations and safety profiles. TNF-α inhibitors are recommended over secukinumab as the initial choice for biologic treatment, due to the availability of larger amount of data, as well as longer and greater clinical experience with these agents. Molecular and genomic biomarkers which are central and crucial to implementation of personalized medicine in its modern context are not yet available for the treatment of axial spondyloarthritis; therefore, personalized care of such patients can currently be practiced mainly on the basis of general patient characteristics, patient preferences, and clinical findings.


Ankylosing spondylitis Axial spondyloarthritis Personalized medicine Personalized care Treatment Management 



I sincerely acknowledge and thank Dr. Muhammad Asim Khan for reviewing the article.

Compliance with Ethical Standards

Conflict of Interest

Nurullah Akkoc declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Recently published papers of particular interest have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Akkoc N, Khan MA. Chapter 10—Epidemiology of ankylosing spondylitis and related spondyloarthropathies A2 - Weisman, Michael H. In: Dvd H, Reveille JD, editors. Ankylosing spondylitis and the spondyloarthropathies. Philadelphia: Mosby; 2006. p. 117–31.Google Scholar
  2. 2.
    Hanson A, Brown MA. Genetics and the causes of ankylosing spondylitis. Rheum Dis Clin N Am. 2017;43(3):401–14. Scholar
  3. 3.
    Akkoc N, Yarkan H, Kenar G, Khan MA. Ankylosing spondylitis: HLA-B*27-positive versus HLA-B*27-negative disease. Curr Rheumatol Rep. 2017;19(5):26. Scholar
  4. 4.
    van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27(4):361–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Wang R, Gabriel SE, Ward MM. Progression of nonradiographic axial spondyloarthritis to ankylosing spondylitis: a population-based cohort study. Arthritis Rheumatol. 2016;68(6):1415–21. Scholar
  6. 6.
    Khan MA, van der Linden SM, Kushner I, Valkenburg HA, Cats A. Spondylitic disease without radiologic evidence of sacroiliitis in relatives of HLA-B27 positive ankylosing spondylitis patients. Arthritis Rheum. 1985;28(1):40–3.CrossRefPubMedGoogle Scholar
  7. 7.
    Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum. 2005;52(4):1000–8. Scholar
  8. 8.
    Rudwaleit M, van der Heijde D, Landewe R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009;68(6):777–83. Scholar
  9. 9.
    Robinson PC, Wordsworth BP, Reveille JD, Brown MA. Axial spondyloarthritis: a new disease entity, not necessarily early ankylosing spondylitis. Ann Rheum Dis. 2012;72(2):162–4. Scholar
  10. 10.
    Akkoc N, Khan MA. Looking into the new ASAS classification criteria for axial spondyloarthritis through the other side of the glass. Curr Rheumatol Rep. 2015;17(6):515. Scholar
  11. 11.
    van der Linden S, Akkoc N, Brown MA, Robinson PC, Khan MA. The ASAS criteria for axial spondyloarthritis: strengths, weaknesses, and proposals for a way forward. Curr Rheumatol Rep. 2015;17(9):62. Scholar
  12. 12.
    Corbett M, Soares M, Jhuti G, Rice S, Spackman E, Sideris E, et al. Tumour necrosis factor-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review and economic evaluation. Health Technol Assess. 2016;20(9):1–334, v-vi.
  13. 13.
    Deodhar A, Reveille JD, van den Bosch F, Braun J, Burgos-Vargas R, Caplan L, et al. The concept of axial spondyloarthritis: joint statement of the Spondyloarthritis research and treatment network and the Assessment of SpondyloArthritis international Society in response to the US Food and Drug Administration’s comments and concerns. Arthritis Rheumatol. 2014;66(10):2649–56. Scholar
  14. 14.
    •• Ward MM, Deodhar A, Akl EA, Lui A, Ermann J, Gensler LS, et al. 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. 2016;68(2):282–98. Evidence recommendations by the ACR/SAA/SPARTAN for the treatment of AS and nr-axSpA, presented in two parts. The recommendations for nr-axSpA were identical to those for AS, except for the recommendation on TNF inhibitors. Because they are the only therapeutics tested in a clinical trial in nr-axSpA.CrossRefPubMedGoogle Scholar
  15. 15.
    •• van der Heijde D, Ramiro S, Landewe R, Baraliakos X, Van den Bosch F, Sepriano A, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76(6):978–91. An update to the previous ASAS/EULAR management recommedations for AS. This new version presents one set of management recommendations for axSpA. Importantly, secukinumab is included in the recommendations.CrossRefPubMedGoogle Scholar
  16. 16.
    Zochling J, van der Heijde D, Burgos-Vargas R, Collantes E, Davis JC Jr, Dijkmans B, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2006;65(4):442–52. Scholar
  17. 17.
    Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2011;70(6):896–904. Scholar
  18. 18.
    Pokorska-Bocci A, Stewart A, Sagoo GS, Hall A, Kroese M, Burton H. “Personalized medicine”: what’s in a name? Personalized Med. 2014;11(2):197–210.CrossRefGoogle Scholar
  19. 19.
    Schleidgen S, Klingler C, Bertram T, Rogowski WH, Marckmann G. What is personalized medicine: sharpening a vague term based on a systematic literature review. BMC Med Ethics. 2013;14:55. Scholar
  20. 20.
    Simmons LA, Dinan MA, Robinson TJ, Snyderman R. Personalized medicine is more than genomic medicine: confusion over terminology impedes progress towards personalized healthcare. Personalized Med. 2011;9(1):85–91. Scholar
  21. 21.
    Nicholls SG, Wilson BJ, Castle D, Etchegary H, Carroll JC. Personalized medicine and genome-based treatments: why personalized medicine ≠ individualized treatments. Clin Ethics. 2014;9(4):135–44. Scholar
  22. 22.
    Hamburg MA. Paving the way for personalized medicine: FDA’s role in the new era of medical product development. FDA Maryland. 2013.Google Scholar
  23. 23.
    Dagfinrud H, Kvien TK, Hagen KB. Physiotherapy interventions for ankylosing spondylitis. Cochrane Database Syst Rev. 2008;1:CD002822. Scholar
  24. 24.
    • Millner JR, Barron JS, Beinke KM, Butterworth RH, Chasle BE, Dutton LJ, et al. Exercise for ankylosing spondylitis: an evidence-based consensus statement. Semin Arthritis Rheum. 2016;45(4):411–27. This evidence based consensus statement provide specific recommendations on a range of topics relevant for exercise prescription. Although developed primarily for use by Australian health professionals and patients, the recommendations can be used also in other countries, particularly where spa facilities are not available.CrossRefPubMedGoogle Scholar
  25. 25.
    Levitova A, Hulejova H, Spiritovic M, Pavelka K, Senolt L, Husakova M. Clinical improvement and reduction in serum calprotectin levels after an intensive exercise programme for patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis. Arthritis Res Ther. 2016;18(1):275. Scholar
  26. 26.
    Husakova M, Siebuhr AS, Pavelka K, Spiritovic M, Bay-Jensen AC, Levitova A. Changes of patient-reported outcomes and protein fingerprint biomarkers after exercise therapy for axial spondyloarthritis. Clin Rheumatol. 2017;
  27. 27.
    Baraliakos X, Kiltz U, Peters S, Appel H, Dybowski F, Igelmann M, et al. Efficiency of treatment with non-steroidal anti-inflammatory drugs according to current recommendations in patients with radiographic and non-radiographic axial spondyloarthritis. Rheumatology. 2017;56(1):95–102. Scholar
  28. 28.
    Sieper J, Klopsch T, Richter M, Kapelle A, Rudwaleit M, Schwank S, et al. Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: results of a 12-week randomised, double-blind, controlled study. Ann Rheum Dis. 2008;67(3):323–9. Scholar
  29. 29.
    Walker C, Essex MN, Li C, Park PW. Celecoxib versus diclofenac for the treatment of ankylosing spondylitis: 12-week randomized study in Norwegian patients. J Int Med Res. 2016;44(3):483–95. Scholar
  30. 30.
    van der Heijde D, Baraf HS, Ramos-Remus C, Calin A, Weaver AL, Schiff M, et al. Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: results of a fifty-two-week, randomized, controlled study. Arthritis Rheum. 2005;52(4):1205–15.CrossRefPubMedGoogle Scholar
  31. 31.
    Kroon FP, van der Burg LR, Ramiro S, Landewe RB, Buchbinder R, Falzon L, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis). Cochrane Database Syst Rev. 2015;7:CD010952. Scholar
  32. 32.
    Wang H, Zuo D, Sun M, Hua Y, Cai Z. Randomized, placebo controlled and double-blind trials of efficacy and safety of adalimumab for treating ankylosing spondylitis: a meta-analysis. Int J Rheum Dis. 2014;17(2):142–8. Scholar
  33. 33.
    Song IH, Poddubnyy DA, Rudwaleit M, Sieper J. Benefits and risks of ankylosing spondylitis treatment with nonsteroidal antiinflammatory drugs. Arthritis Rheum. 2008;58(4):929–38.CrossRefPubMedGoogle Scholar
  34. 34.
    Sieper J, Lenaerts J, Wollenhaupt J, Rudwaleit M, Mazurov VI, Myasoutova L, et al. 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. 2014;73(1):101–7. Scholar
  35. 35.
    Wanders A, van der Heijde D, Landewe R, Behier JKM, Calin A, Olivieri I, et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis—a randomized clinical trial. Arthritis Rheum. 2005;52(6):1756–65. Scholar
  36. 36.
    Burmester G, Lanas A, Biasucci L, Hermann M, Lohmander S, Olivieri I, et al. The appropriate use of non-steroidal anti-inflammatory drugs in rheumatic disease: opinions of a multidisciplinary European expert panel. Ann Rheum Dis. 2011;70(5):818–22. Scholar
  37. 37.
    Nissen SE, Yeomans ND, Solomon DH, Luscher TF, Libby P, Husni ME, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med. 2016;375(26):2519–29. Scholar
  38. 38.
    Lee YS, Kim H, Wu TX, Wang XM, Dionne RA. Genetically mediated interindividual variation in analgesic responses to cyclooxygenase inhibitory drugs. Clin Pharmacol Ther. 2006;79(5):407–18. Scholar
  39. 39.
    Agundez JA, Garcia-Martin E, Martinez C. Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine? Expert Opin Drug Metab Toxicol. 2009;5(6):607–20. Scholar
  40. 40.
    Domiati S, Ghoneim A. Celecoxib for the right person at the right dose and right time: an updated overview. Springer Sci Rev. 2015;3(2):137–40. Scholar
  41. 41.
    Haibel H, Fendler C, Listing J, Callhoff J, Braun J, Sieper J. Efficacy of oral prednisolone in active ankylosing spondylitis: results of a double-blind, randomised, placebo-controlled short-term trial. Ann Rheum Dis. 2013;73:243–6. Scholar
  42. 42.
    Bandinelli F, Scazzariello F, Pimenta da Fonseca E, Barreto Santiago M, Marcassa C, Nacci F, et al. Low-dose modified-release prednisone in axial spondyloarthritis: 3-month efficacy and tolerability. Drug Des Devel Ther. 2016;10:3717–24. Scholar
  43. 43.
    • Zhang YP, Gong Y, Zeng QY, Hou ZD, Xiao ZY. A long-term, observational cohort study on the safety of low-dose glucocorticoids in ankylosing spondylitis: adverse events and effects on bone mineral density, blood lipid and glucose levels and body mass index. BMJ Open. 2015;5(6):e006957. This is a large-scale long-term observational study that reports on the safety of low dose GC use in AS. The authors conclude that low-dose GCs have only limited adverse effects in the long term.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Chen J, Lin S, Liu C. Sulfasalazine for ankylosing spondylitis. Cochrane Database Syst Rev. 2014;11:CD004800. Scholar
  45. 45.
    Chen J, Liu C, Lin J. Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev. 2006;4:CD004524. Scholar
  46. 46.
    Fagerli KM, van der Heijde D, Heiberg MS, Wierod A, Kalstad S, Rodevand E, et al. Is there a role for sulphasalazine in axial spondyloarthritis in the era of TNF inhibition? Data from the NOR-DMARD longitudinal observational study. Rheumatology (Oxford). 2014;53(6):1087–94. Scholar
  47. 47.
    Song IH, Hermann K, Haibel H, Althoff CE, Listing J, Burmester G, et al. Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48-week randomised controlled trial. Ann Rheum Dis. 2011;70(4):590–6. Scholar
  48. 48.
    Braun J, van der Horst-Bruinsma IE, Huang F, Burgos-Vargas R, Vlahos B, Koenig AS, et al. Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis: a randomized, double-blind trial. Arthritis Rheum. 2011;63(6):1543–51. Scholar
  49. 49.
    Heinonen AV, Aaltonen KJ, Joensuu JT, Lahteenmaki JP, Pertovaara MI, Romu MK, et al. Effectiveness and drug survival of TNF inhibitors in the treatment of ankylosing spondylitis: a prospective cohort study. J Rheumatol. 2015;42(12):2339–46. Scholar
  50. 50.
    Breban M, Ravaud P, Claudepierre P, Baron G, Henry YD, Hudry C, et al. Maintenance of infliximab treatment in ankylosing spondylitis: results of a one-year randomized controlled trial comparing systematic versus on-demand treatment. Arthritis Rheum. 2008;58(1):88–97. Scholar
  51. 51.
    Li EK, Griffith JF, Lee VW, Wang YX, Li TK, Lee KK, et al. Short-term efficacy of combination methotrexate and infliximab in patients with ankylosing spondylitis: a clinical and magnetic resonance imaging correlation. Rheumatology (Oxford). 2008;47(9):1358–63.CrossRefGoogle Scholar
  52. 52.
    van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006;54(7):2136–46. Scholar
  53. 53.
    Landewe R, Braun J, Deodhar A, Dougados M, Maksymowych WP, Mease PJ, et al. 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. 2014;73(1):39–47. Scholar
  54. 54.
    Landewe RBM, Rudwaleit M, van der Heijde D, Dougados M, Maksymowych WP, Braun J, et al. Effect of certolizumab pegol on signs and symptoms of ankylosing spondyltitis and non-radiographic axial spondyloarthritis: 24 week results of a double blind randomized placebo-controlled phase 3 axial spondyloarthritis study. Arthritis Rheum. 2012;64(10):S336–S7.Google Scholar
  55. 55.
    Davis JC Jr, Van Der Heijde D, Braun J, Dougados M, Cush J, Clegg DO, et al. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum. 2003;48(11):3230–6. Scholar
  56. 56.
    Food and Drug Administration. 24 June 2003 Arthritis Advisory Committee Meeting Briefing Document ENBREL (etanercept). Accessed 24 Nov 2017.
  57. 57.
    van der Heijde D, Da Silva JC, Dougados M, Geher P, van der Horst-Bruinsma I, Juanola X, et al. Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis. Ann Rheum Dis. 2006;65(12):1572–7. Scholar
  58. 58.
    Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008;58(11):3402–12. Scholar
  59. 59.
    Braun J, Davis JC, Van der Heijde D, Diekman L, Sieper J, Kim SI, et al. Golimumab, a new, human, TNF-alpha antibody administered as a monthly subcutaneous injection in ankylosing spondylitis (AS): 24-week efficacy and safety results of the randomized, placebocontrolled GO-RAISE study. Arthritis Rheum. 2007;56(12):4236–7.Google Scholar
  60. 60.
    Deodhar AA, Reveille JD, Harrison DD, Kim L, Lo KH, Hsia EC. Safety and efficacy of intravenous golimumab in adult patients with active ankylosing spondylitis: results through week 28 [abstract]. Arthritis Rheumatol. 2016;68(Suppl 10).Google Scholar
  61. 61.
    van der Heijde D, Dijkmans B, Geusens P, Sieper J, DeWoody K, Williamson P, et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum. 2005;52(2):582–91. Scholar
  62. 62.
    •• Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, et al. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med. 2015;373(26):2534–48. This publication reports the efficacy and safety data from MEASURE 1 and 2, two phase III clinical trials with secukinumab, conducted in patients with AS. Both trials, provide convincing evidence for efficacy and safety of secukinumab in AS.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Sieper J, van der Heijde D, Dougados M, Mease PJ, Maksymowych WP, Brown MA, et al. Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis. 2013;72(6):815–22. Scholar
  64. 64.
    Dougados M, van der Heijde D, Sieper J, Braun J, Maksymowych WP, Citera G, et al. 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. 2014;66(8):2091–102. Scholar
  65. 65.
    Dougados M, van der Heijde D, Sieper J, Braun J, Maksymowych WP, Citera G, et al. Safety and efficacy of etanercept in early non-radiographic axial spondyloarthritis: a randomized, double-blind, placebo-controlled trial at 24 weeks. Arthritis Rheum. 2013;65:S642–S3.Google Scholar
  66. 66.
    Sieper J, van der Heijde D, Dougados M, Maksymowych WP, Scott BB, Boice JA, et al. A randomized, double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2015;67(10):2702–12. Scholar
  67. 67.
    Akkoc N, Khan MA. Treatment of patients with nonradiographic axial spondyloarthritis who have negative magnetic resonance imaging results and normal C-reactive protein levels at baseline: comment on the article by Ward et al. Arthritis Rheumatol. 2016;68(6):1563. Scholar
  68. 68.
    Sepriano A, Regel A, van der Heijde D, Braun J, Baraliakos X, Landewe R, et al. Efficacy and safety of biological and targeted-synthetic DMARDs: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. RMD Open. 2017;3(1):e000396. Scholar
  69. 69.
    Fabiani C, Vitale A, Lopalco G, Iannone F, Frediani B, Cantarini L. Different roles of TNF inhibitors in acute anterior uveitis associated with ankylosing spondylitis: state of the art. Clin Rheumatol. 2016;35(11):2631–8. Scholar
  70. 70.
    Gossec L, Smolen JS, Gaujoux-Viala C, Ash Z, Marzo-Ortega H, van der Heijde D, et al. European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. Ann Rheum Dis. 2012;71(1):4–12. Scholar
  71. 71.
    Xie X, Li F, Chen JW, Wang J. Risk of tuberculosis infection in anti-TNF-alpha biological therapy: from bench to bedside. J Microbiol Immunol Infect. 2014;47(4):268–74. Scholar
  72. 72.
    Flint J, Panchal S, Hurrell A, van de Venne M, Gayed M, Schreiber K, et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford). 2016;55(9):1693–7. Scholar
  73. 73.
    Gotestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75(5):795–810. Scholar
  74. 74.
    •• Maksymowych WP. An update on biomarker discovery and use in axial spondyloarthritis. Expert Rev Mol Diagn. 2017:1–10. doi: An excellent comprehensive review on biomarker studies in AS.
  75. 75.
    de Winter J, van de Sande M, Baerlecken N, Berg I, Ramonda R, van der Heijde D et al. Diagnostic value of anti-CD74 antibodies in early axial spondyloarthritis: data from the Spondyloarthritis Caught Early (SPACE) cohort [abstract]. Arthritis Rheumatol. 2017;69 (suppl 10).Google Scholar
  76. 76.
    Maneiro JR, Souto A, Salgado E, Mera A, Gomez-Reino JJ. Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis. RMD Open. 2015;1(1):e000017. Scholar
  77. 77.
    Vastesaeger N, van der Heijde D, Inman RD, Wang Y, Deodhar A, Hsu B, et al. Predicting the outcome of ankylosing spondylitis therapy. Ann Rheum Dis. 2011;70(6):973–81. Scholar
  78. 78.
    Sieper J, van der Heijde D, Dougados M, Brown LS, Lavie F, Pangan AL. Early response to adalimumab predicts long-term remission through 5 years of treatment in patients with ankylosing spondylitis. Ann Rheum Dis. 2012;71(5):700–6. Scholar
  79. 79.
    van der Heijde D, Deodhar A, Fleischmann R, Mease PJ, Rudwaleit M, Nurminen T, et al. Early disease activity or clinical response as predictors of long-term outcomes with certolizumab pegol in axial spondyloarthritis or psoriatic arthritis. Arthritis Care Res (Hoboken). 2017;69(7):1030–9. Scholar
  80. 80.
    • Navarro-Compan V, Plasencia-Rodriguez C, de Miguel E, Balsa A, Martin-Mola E, Seoane-Mato D, et al. Anti-TNF discontinuation and tapering strategies in patients with axial spondyloarthritis: a systematic literature review. Rheumatology (Oxford). 2016;55(7):1188–94. A systematic literature review that evaluates anti-TNF discontinuation and tapering strategies in axial spondyloarthritis. The authors conclude that a tapering strategy for anti-TNF therapy in may be successful in most patientsCrossRefGoogle Scholar
  81. 81.
    Edwards CJ, Fautrel B, Schulze-Koops H, Huizinga TWJ, Kruger K. Dosing down with biologic therapies: a systematic review and clinicians' perspective. Rheumatology (Oxford). 2017;56(11):1847–56. Scholar
  82. 82.
    Baeten D, Blanco R, Geusens P, Sieper J, Tseng JC, Martin R et al. Secukinumab provides sustained improvements in the signs and symptoms of active ankylosing spondylitis in anti-TNF-naive patients and those previously exposed to anti-TNF therapy: 52-week results from two randomized, double-blind, placebo-controlled phase 3 trials [abstract]. Arthritis & Rheumatology. 2015;67(suppl 10).Google Scholar
  83. 83.
    • Sieper J, Deodhar A, Marzo-Ortega H, Aelion JA, Blanco R, Jui-Cheng T, et al. Secukinumab efficacy in anti-TNF-naive and anti-TNF-experienced subjects with active ankylosing spondylitis: results from the MEASURE 2 Study. Ann Rheum Dis. 2017;76(3):571. This pre-specified subgroup analysis of MEASURE-2 trial report that secukinumab is effective both in TNF inhibitor-naïve and TNF inhibitor inadeqaute responder AS patients, but with better results in anti-TNF-naïve patients. A limitation of the study is that it does not present any information for primary versus secondary treatment failure or intolerance categories–92.CrossRefPubMedGoogle Scholar
  84. 84.
    Baeten D, Baraliakos X, Braun J, Sieper J, Emery P, van der Heijde D, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;382(9906):1705–13. Scholar
  85. 85.
    Baraliakos X, Braun J, Sieper J, Baeten DL, Readie A, Ligozio G, et al. THU0233 secukinumab reduces sacroiliac joint and spinal inflammation in patients with ankylosing spondylitis: MRI data from a phase 3 randomized, double-blind, placebo-controlled study (MEASURE 1). Ann Rheum Dis. 2015;74(Suppl 2):281–28281. Scholar
  86. 86.
    Blauvelt A. Safety of secukinumab in the treatment of psoriasis. Expert Opin Drug Saf. 2016;15(10):1413–20. Scholar
  87. 87.
    Kammuller M, Tsai TF, Griffiths CE, Kapoor N, Kolattukudy PE, Brees D, et al. Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections. Clin Transl Immunol. 2017;6(8):e152. Scholar
  88. 88.
    Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins PD, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61(12):1693–700. Scholar
  89. 89.
    Dick AD, Tugal-Tutkun I, Foster S, Zierhut M, Melissa Liew SH, Bezlyak V, et al. Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology. 2013;120(4):777–87. Scholar
  90. 90.
    Song IH, Heldmann F, Rudwaleit M, Haibel H, Weiss A, Braun J, et al. Treatment of active ankylosing spondylitis with abatacept: an open-label, 24-week pilot study. Ann Rheum Dis. 2011;70(6):1108–10. Scholar
  91. 91.
    Song IH, Heldmann F, Rudwaleit M, Listing J, Appel H, Braun J, et al. Different response to rituximab in tumor necrosis factor blocker-naive patients with active ankylosing spondylitis and in patients in whom tumor necrosis factor blockers have failed: a twenty-four-week clinical trial. Arthritis Rheum. 2010;62(5):1290–7. Scholar
  92. 92.
    Song IH, Heldmann F, Rudwaleit M, Listing J, Appel H, Haug-Rost I, et al. One-year follow-up of ankylosing spondylitis patients responding to rituximab treatment and re-treated in case of a flare. Ann Rheum Dis. 2013;72(2):305–6. Scholar
  93. 93.
    Tan AL, Marzo-Ortega H, O'Connor P, Fraser A, Emery P, McGonagle D. Efficacy of anakinra in active ankylosing spondylitis: a clinical and magnetic resonance imaging study. Ann Rheum Dis. 2004;63(9):1041–5.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Haibel H, Rudwaleit M, Listing J, Sieper J. Open label trial of anakinra in active ankylosing spondylitis over 24 weeks. Ann Rheum Dis. 2005;64(2):296–8. Scholar
  95. 95.
    Sieper J, Porter-Brown B, Thompson L, Harari O, Dougados M. Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials. Ann Rheum Dis. 2014;73(1):95–100. Scholar
  96. 96.
    Sieper J, Braun J, Kay J, Badalamenti S, Radin AR, Jiao L, et al. Sarilumab for the treatment of ankylosing spondylitis: results of a phase II, randomised, double-blind, placebo-controlled study (ALIGN). Ann Rheum Dis. 2014;74:1051–7. Scholar
  97. 97.
    Poddubnyy D, Hermann KG, Callhoff J, Listing J, Sieper J. Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS). Ann Rheum Dis. 2014;73(5):817–23. Scholar
  98. 98.
    van der Heijde D, Deodhar A, Wei JC, Drescher E, Fleishaker D, Hendrikx T, et al. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis. 2017;76(8):1340–7. Scholar
  99. 99.
    • Schork NJ. Personalized medicine: time for one-person trials. Nature. 2015;520(7549):609–11. A commentary article discussing about the types of trial designs that are needed for personalized medicineCrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Nurullah Akkoc
    • 1
  1. 1.IzmirTurkey

Personalised recommendations