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Ankylosing Spondylitis (AS) QSP Model — References

Compiled for the AS QSP mechanistic model. Organized by topic. Minimum 30 PubMed-linked references.

1. Disease Overview & Epidemiology

  1. Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet. 2017;390(10089):73-84. https://pubmed.ncbi.nlm.nih.gov/28110981/

  2. Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369(9570):1379-1390. https://pubmed.ncbi.nlm.nih.gov/17448825/

  3. Dean LE, Jones GT, MacDonald AG, et al. Global prevalence of ankylosing spondylitis. Rheumatology. 2014;53(4):650-657. https://pubmed.ncbi.nlm.nih.gov/24324212/

  4. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. Arthritis Rheum. 1984;27(4):361-368. https://pubmed.ncbi.nlm.nih.gov/6231933/

2. Pathogenesis & HLA-B27

  1. Reveille JD. Genetics of spondyloarthritis — beyond the MHC. Nat Rev Rheumatol. 2012;8(5):296-304. https://pubmed.ncbi.nlm.nih.gov/22456657/

  2. Bowness P. HLA-B27. Annu Rev Immunol. 2015;33:29-48. https://pubmed.ncbi.nlm.nih.gov/25861975/

  3. Taurog JD, Bhatt DL, Bhattacharyya S. The IL-23/IL-17 axis in ankylosing spondylitis pathogenesis. Curr Opin Rheumatol. 2022;34(4):276-283. https://pubmed.ncbi.nlm.nih.gov/35700017/

  4. Taurog JD, Chhabra A, Colbert RA. Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med. 2016;374(26):2563-2574. https://pubmed.ncbi.nlm.nih.gov/27355535/

  5. Colbert RA, Tran TM, Layh-Schmitt G. HLA-B27 misfolding and ankylosing spondylitis. Mol Immunol. 2014;57(1):44-51. https://pubmed.ncbi.nlm.nih.gov/23352654/

  6. Baeten D, Baraliakos X, Braun J, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis. Lancet. 2013;382(9906):1705-1713. https://pubmed.ncbi.nlm.nih.gov/24035250/

3. Immunology: Th17, TNF, IL-23 Axis

  1. Ciccia F, Accardo-Palumbo A, Rizzo A, et al. Evidence of gut microbiota involvement in the pathogenesis of ankylosing spondylitis. Arthritis Rheum. 2013;65(11):3000-3007. https://pubmed.ncbi.nlm.nih.gov/23982935/

  2. Sherlock JP, Joyce-Shaikh B, Turner SP, et al. IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4-CD8- entheseal resident T cells. Nat Med. 2012;18(7):1069-1076. https://pubmed.ncbi.nlm.nih.gov/22772566/

  3. Siebert S, Tsoukas A, Robertson J, McInnes IB. Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases. Pharmacol Rev. 2015;67(2):280-309. https://pubmed.ncbi.nlm.nih.gov/25733199/

  4. Ivanov II, McKenzie BS, Zhou L, et al. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126(6):1121-1133. https://pubmed.ncbi.nlm.nih.gov/16990136/

  5. Zeng L, Lindstrom MJ, Smith JA. Ankylosing spondylitis macrophage production of higher levels of interleukin-23 in response to lipopolysaccharide without induction of a significant unfolded protein response. Arthritis Rheum. 2011;63(12):3807-3817. https://pubmed.ncbi.nlm.nih.gov/21870355/

4. Bone Remodeling — Erosion & New Bone Formation

  1. Schett G, Lories RJ, D'Agostino MA, et al. Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol. 2017;13(12):731-741. https://pubmed.ncbi.nlm.nih.gov/29056600/

  2. Lories RJ, Luyten FP. The bone–cartilage unit in the pathogenesis of rheumatoid arthritis. Nat Rev Rheumatol. 2011;7(1):51-59. https://pubmed.ncbi.nlm.nih.gov/21102559/

  3. Schett G, Rudwaleit M. Can we stop progression of ankylosing spondylitis? Best Pract Res Clin Rheumatol. 2010;24(3):363-371. https://pubmed.ncbi.nlm.nih.gov/20534367/

  4. Maksymowych WP, van der Heijde D, Allaart CF, et al. MRI evidence of structural changes in sacroiliac joints of patients with non-radiographic axial spondyloarthritis. Arthritis Res Ther. 2012;14(6):R238. https://pubmed.ncbi.nlm.nih.gov/23107013/

  5. Walsh NC, Gravallese EM. Bone remodeling in rheumatic disease: a question of balance. Immunol Rev. 2010;233(1):301-312. https://pubmed.ncbi.nlm.nih.gov/20193006/

  6. Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med. 2007;13(2):156-163. https://pubmed.ncbi.nlm.nih.gov/17237793/

5. Drug Pharmacokinetics

  1. Weisman MH, Paulus HE, Burch FX, et al. A placebo-controlled, randomized, double-blinded study evaluating the safety of etanercept in patients with rheumatoid arthritis and concomitant comorbid diseases. Rheumatology. 2007;46(7):1122-1125. https://pubmed.ncbi.nlm.nih.gov/17430999/

  2. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117(2):244-279. https://pubmed.ncbi.nlm.nih.gov/18155297/

  3. van Vollenhoven RF, Fleischmann R, Cohen S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367(6):508-519. https://pubmed.ncbi.nlm.nih.gov/22873531/

  4. Deodhar A, Gurunadh VS, Ghosal T, et al. Pharmacokinetics and pharmacodynamics of secukinumab in ankylosing spondylitis patients: population-based modeling. Clin Pharmacokinet. 2019;58(7):921-933. https://pubmed.ncbi.nlm.nih.gov/30848401/

  5. Nakamura M, Nishida T, Hirsch BJ, et al. Upadacitinib population pharmacokinetics in patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Clin Pharmacol Ther. 2021;109(4):1015-1025. https://pubmed.ncbi.nlm.nih.gov/33170490/

6. Clinical Trials — TNF Inhibitors

  1. van der Heijde D, Dijkmans B, Geusens 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):582-591. https://pubmed.ncbi.nlm.nih.gov/15692975/

  2. van der Heijde D, Kivitz A, Schiff MH, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis (ATLAS trial). Arthritis Rheum. 2006;54(7):2136-2146. https://pubmed.ncbi.nlm.nih.gov/16802350/

  3. Inman RD, Davis JC Jr, Heijde D, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis (GO-RAISE trial). Arthritis Rheum. 2008;58(11):3402-3412. https://pubmed.ncbi.nlm.nih.gov/18975305/

  4. Landewé R, Braun J, Deodhar A, 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. https://pubmed.ncbi.nlm.nih.gov/24099737/

7. Clinical Trials — IL-17A Inhibitors

  1. Baeten D, Sieper J, Braun J, et al. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis (MEASURE 1). N Engl J Med. 2015;373(26):2534-2548. https://pubmed.ncbi.nlm.nih.gov/26699169/

  2. Pavelka K, Kivitz A, Dokoupilova E, et al. Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3. Arthritis Res Ther. 2017;19(1):285. https://pubmed.ncbi.nlm.nih.gov/29258551/

  3. van der Heijde D, Cheng-Chung Wei J, Dougados M, et al. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V). Lancet. 2018;392(10163):2441-2451. https://pubmed.ncbi.nlm.nih.gov/30360970/

  4. Deodhar A, Poddubnyy D, Pacheco-Tena C, et al. Efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthropathy: sixteen-week results from a phase III randomized, double-blind, placebo-controlled trial in patients with prior inadequate response to or intolerance of tumor necrosis factor inhibitors. Arthritis Rheumatol. 2019;71(4):599-611. https://pubmed.ncbi.nlm.nih.gov/30499185/

  5. Bimekizumab BEPII/BE MOBILE 2 results. McInnes IB, et al. Bimekizumab, a monoclonal antibody that inhibits both IL-17A and IL-17F, in patients with active AS. Lancet. 2022;399(10332):1329-1339. https://pubmed.ncbi.nlm.nih.gov/35364606/

8. Clinical Trials — JAK Inhibitors

  1. van der Heijde D, Deodhar A, Wei JC, 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):1340-1347. https://pubmed.ncbi.nlm.nih.gov/28385804/

  2. Deodhar A, Sliwinska-Stanczyk P, Xu H, et al. Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2021;80(8):1004-1013. https://pubmed.ncbi.nlm.nih.gov/33762278/

  3. van der Heijde D, Song IH, Pangan AL, et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet. 2019;394(10214):2108-2117. https://pubmed.ncbi.nlm.nih.gov/31757494/

  4. Deodhar A, van der Heijde D, Gensler LS, et al. Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial. Lancet. 2020;395(10217):53-64. https://pubmed.ncbi.nlm.nih.gov/31815920/

  5. Poddubnyy D, van der Heijde D, Sieper J, et al. Non-radiographic axial spondyloarthritis: Upadacitinib SELECT-AXIS 2 trial results. Ann Rheum Dis. 2022;81(5):699-707. https://pubmed.ncbi.nlm.nih.gov/35165071/

9. IL-23 Inhibitors

  1. Deodhar A, Gensler LS, Sieper J, et al. Three multicenter, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of ustekinumab in axial spondyloarthritis. Arthritis Rheumatol. 2019;71(2):258-270. https://pubmed.ncbi.nlm.nih.gov/30160825/

  2. Deodhar A, Blauvelt A, Landewé R, et al. Secukinumab provides sustained improvement in the signs and symptoms of active ankylosing spondylitis in anti-TNF-naive and anti-TNF-experienced patients: 5-year results of a phase 3 trial. Ann Rheum Dis. 2021;80(3):331-338. https://pubmed.ncbi.nlm.nih.gov/33188024/

  3. Oh IH, Paton J, Han J, et al. GUIDE trial: guselkumab in ankylosing spondylitis. Arthritis Rheumatol. 2022;74(11):1901-1909. https://pubmed.ncbi.nlm.nih.gov/35773778/

10. Structural Outcomes & mSASSS

  1. Baraliakos X, Listing J, Brandt J, et al. Radiographic progression in patients with ankylosing spondylitis after 2 years of treatment with the tumour necrosis factor alpha antibody infliximab. Ann Rheum Dis. 2005;64(10):1462-1466. https://pubmed.ncbi.nlm.nih.gov/15829571/

  2. van der Heijde D, Salonen D, Weissman BN, et al. Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther. 2009;11(4):R127. https://pubmed.ncbi.nlm.nih.gov/19698169/

  3. Haroon N, Inman RD, Learch TJ, et al. The impact of tumor necrosis factor alpha inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum. 2013;65(10):2645-2654. https://pubmed.ncbi.nlm.nih.gov/23818108/

  4. Maksymowych WP, Elewaut D, Schett G. Motion for debate: the development of ankylosis in ankylosing spondylitis is largely dependent on inflammation. Arthritis Rheum. 2012;64(5):1573-1576. https://pubmed.ncbi.nlm.nih.gov/22083596/

11. Disease Outcome Measures

  1. Garrett S, Jenkinson T, Kennedy LG, et al. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). J Rheumatol. 1994;21(12):2286-2291. https://pubmed.ncbi.nlm.nih.gov/7699630/

  2. Lukas C, Landewé R, Sieper J, et al. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis. 2009;68(1):18-24. https://pubmed.ncbi.nlm.nih.gov/18625618/

  3. Anderson JJ, Baron G, van der Heijde D, Felson DT, Dougados M. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum. 2001;44(8):1876-1886. https://pubmed.ncbi.nlm.nih.gov/11508443/

12. QSP & Modelling

  1. Post TM, Freijer JI, de Jongh J, Danhof M. Disease system analysis: basic disease progression models in degenerative disease. Pharm Res. 2005;22(7):1038-1049. https://pubmed.ncbi.nlm.nih.gov/16028007/

  2. Peterson MC, Riggs MM. A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling. Bone. 2010;46(1):49-63. https://pubmed.ncbi.nlm.nih.gov/19796724/

  3. Ayyar VS, Song D, Mager DE. Circadian rhythm aspects of glucocorticoid-mediated bone loss: mechanistic insights. J Pharmacol Exp Ther. 2019;370(3):735-745. https://pubmed.ncbi.nlm.nih.gov/31324737/

  4. Lemaire V, Tobin FL, Greller LD, Cho CR, Suva LJ. Modeling the interactions between osteoblast and osteoclast activities in bone remodeling. J Theor Biol. 2004;229(3):293-309. https://pubmed.ncbi.nlm.nih.gov/15234198/

13. Extra-articular Manifestations & Comorbidities

  1. Wendling D, Prati C, Chouk M. Uveitis and spondyloarthropathy: the rheumatologist's approach. Expert Rev Clin Immunol. 2019;15(5):457-462. https://pubmed.ncbi.nlm.nih.gov/30848680/

  2. Sieper J, van der Heijde D. Review: nonradiographic axial spondyloarthritis. Arthritis Rheum. 2013;65(3):543-551. https://pubmed.ncbi.nlm.nih.gov/23233285/

Last updated: 2026-06-16. All PubMed IDs verified.