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Published in: Clinical Reviews in Allergy & Immunology 3/2018

01-12-2018

Unmet Needs in Axial Spondyloarthritis

Authors: Ennio Lubrano, Antonia De Socio, Fabio Massimo Perrotta

Published in: Clinical Reviews in Allergy & Immunology | Issue 3/2018

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Abstract

During the past decade, the well-known disease called ankylosing spondylitis has come to be considered as a subset of the broader entity referred as axial spondyloarthritis (axSpA), which also includes non-radiographic axSpA. The need of this new classification was aimed to improve the sensitivity for an early diagnosis, to reduce diagnostic delay, and to allow an early treatment. Although there is improvement in the recognition, the management of patients, and the treatment strategies of axSpA, unmet needs persist. There is still a substantial gap of 5–8 years between the onset of symptoms and the diagnosis of axSpA and, even in patients diagnosed early, 20–40% of them do not respond or have a loss of response to anti-TNF treatment. Moreover, the pathogenesis of the disease and, in particular, the mechanisms of new bone formation are far to be completely understood. Nevertheless, the discovery of IL-23/IL-17 axis with the development of biologic inhibitors, the identification of new subsets of effector cells, together with the interest in the detection of potential biomarkers of bone formation brought the approach to axSpA into a new era. This review is intended to enhance awareness and understanding of axSpA and to identify and discuss the current unmet needs in axSpA, including diagnosis, classification, biomarkers, pathogenesis, management, and treatment strategies.
Literature
1.
go back to reference Gladman DD, Antoni C, Mease P et al (2005) Psoriatic arthritis: epidemiology, clinical features, course and outcome. Ann Rheum Dis 64:14–17 Gladman DD, Antoni C, Mease P et al (2005) Psoriatic arthritis: epidemiology, clinical features, course and outcome. Ann Rheum Dis 64:14–17
2.
go back to reference Palazzi C, D’Angelo S, Lubrano E, Olivieri I (2008) Aortic involvement in ankylosing spondylitis. Clin Exp Rheumatol 26:S131–S134PubMed Palazzi C, D’Angelo S, Lubrano E, Olivieri I (2008) Aortic involvement in ankylosing spondylitis. Clin Exp Rheumatol 26:S131–S134PubMed
3.
go back to reference Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J et al (2009) The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 68:777–783CrossRef Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J et al (2009) The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 68:777–783CrossRef
4.
go back to reference 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 27:361–368CrossRef 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 27:361–368CrossRef
5.
6.
go back to reference Rudwaleit M, Khan MA, Sieper J (2005) The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum 52:1000–1008CrossRef Rudwaleit M, Khan MA, Sieper J (2005) The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum 52:1000–1008CrossRef
7.
go back to reference Sieper J, van der Heijde D (2013) Review: nonradiographic axial spondyloarthritis: new definition of an old disease? Arthritis Rheum 65:543–551CrossRef Sieper J, van der Heijde D (2013) Review: nonradiographic axial spondyloarthritis: new definition of an old disease? Arthritis Rheum 65:543–551CrossRef
8.
go back to reference van der Linden S, Akkoc N, Brown MA, Robinson PC, Khan MA (2015) The ASAS criteria for axial spondyloarthritis: strengths, weaknesses, and proposals for a way forward. Curr Rheumatol Rep. doi:10.1007/s11926-015-0535-y van der Linden S, Akkoc N, Brown MA, Robinson PC, Khan MA (2015) The ASAS criteria for axial spondyloarthritis: strengths, weaknesses, and proposals for a way forward. Curr Rheumatol Rep. doi:10.​1007/​s11926-015-0535-y
9.
go back to reference Wallman JK, Kapetanovic MC, Petersson IF, Geborek P, Kristensen LE (2015) Comparison of non-radiographic axial spondyloarthritis and ankylosing spondylitis patients baseline characteristics, treatment adherence, and development of clinical variables during three years of anti-TNF therapy in clinical practice. Arthritis Res Ther 17:378. doi:10.1186/s13075-015-0897-6 CrossRefPubMedPubMedCentral Wallman JK, Kapetanovic MC, Petersson IF, Geborek P, Kristensen LE (2015) Comparison of non-radiographic axial spondyloarthritis and ankylosing spondylitis patients baseline characteristics, treatment adherence, and development of clinical variables during three years of anti-TNF therapy in clinical practice. Arthritis Res Ther 17:378. doi:10.​1186/​s13075-015-0897-6 CrossRefPubMedPubMedCentral
10.
go back to reference Moltó A, Paternotte S, van der Heijde D, Claudepierre P, Rudwaleit M, Dougados M (2015) Evaluation of the validity of the different arms of the ASAS set of criteria for axial spondyloarthritis and description of the different imaging abnormalities suggestive of spondyloarthritis: data from the DESIR cohort. Ann Rheum Dis 74:746–751CrossRef Moltó A, Paternotte S, van der Heijde D, Claudepierre P, Rudwaleit M, Dougados M (2015) Evaluation of the validity of the different arms of the ASAS set of criteria for axial spondyloarthritis and description of the different imaging abnormalities suggestive of spondyloarthritis: data from the DESIR cohort. Ann Rheum Dis 74:746–751CrossRef
11.
go back to reference Akkoc N, Khan MA (2016) ASAS classification criteria for axial spondyloarthritis: time to modify. Clin Rheumatol 35:1415–1423CrossRef Akkoc N, Khan MA (2016) ASAS classification criteria for axial spondyloarthritis: time to modify. Clin Rheumatol 35:1415–1423CrossRef
12.
go back to reference Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Märker-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 70:1369–1374CrossRef Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Märker-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 70:1369–1374CrossRef
13.
go back to reference Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ (2014) Global prevalence of ankylosing spondylitis. Rheumatology (Oxford) 53:650–657CrossRef Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ (2014) Global prevalence of ankylosing spondylitis. Rheumatology (Oxford) 53:650–657CrossRef
15.
go back to reference Poddubnyy D, van Tubergen A, Landewé R, Sieper J, van der Heijde D (2015) Assessment of SpondyloArthritis international Society (ASAS). Development of an ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis. Ann Rheum Dis 74:1483–1487CrossRef Poddubnyy D, van Tubergen A, Landewé R, Sieper J, van der Heijde D (2015) Assessment of SpondyloArthritis international Society (ASAS). Development of an ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis. Ann Rheum Dis 74:1483–1487CrossRef
16.
go back to reference Feldtkeller E, Khan MA, van der Heijde D et al (2003) Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol Int 23:61–66PubMed Feldtkeller E, Khan MA, van der Heijde D et al (2003) Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol Int 23:61–66PubMed
17.
go back to reference Poddubnyy D, Vahldiek J, Spiller I et al (2011) Evaluation of 2 screening strategies for early identification of patients with axial spondyloarthritis in primary care. J Rheumatol 38:2452–2460CrossRef Poddubnyy D, Vahldiek J, Spiller I et al (2011) Evaluation of 2 screening strategies for early identification of patients with axial spondyloarthritis in primary care. J Rheumatol 38:2452–2460CrossRef
18.
go back to reference Sieper J, Srinivasan S, Zamani O et al (2013) Comparison of two referral strategies for diagnosis of axial spondyloarthritis: the Recognising and Diagnosing Ankylosing Spondylitis Reliably (RADAR) study. Ann Rheum Dis 72:1621–1627CrossRef Sieper J, Srinivasan S, Zamani O et al (2013) Comparison of two referral strategies for diagnosis of axial spondyloarthritis: the Recognising and Diagnosing Ankylosing Spondylitis Reliably (RADAR) study. Ann Rheum Dis 72:1621–1627CrossRef
19.
go back to reference Rudwaleit M, van der Heijde D, Khan MA, Braun J, Sieper J (2004) How to diagnose axial spondyloarthritis early. Ann Rheum Dis 63:535–543CrossRef Rudwaleit M, van der Heijde D, Khan MA, Braun J, Sieper J (2004) How to diagnose axial spondyloarthritis early. Ann Rheum Dis 63:535–543CrossRef
20.
go back to reference van den Berg R, de Hooge M, Rudwaleit M, et al (2013) ASAS modification of the Berlin algorithm for diagnosing axial spondyloarthritis: results from the SPondyloArthritis Caught Early (SPACE)-cohort and from the Assessment of SpondyloArthritis international Society (ASAS)-cohort. Ann Rheum Disb72:1646–1653 van den Berg R, de Hooge M, Rudwaleit M, et al (2013) ASAS modification of the Berlin algorithm for diagnosing axial spondyloarthritis: results from the SPondyloArthritis Caught Early (SPACE)-cohort and from the Assessment of SpondyloArthritis international Society (ASAS)-cohort. Ann Rheum Disb72:1646–1653
21.
go back to reference Reveille JD, Hirsch R, Dillon CF, Carroll MD, Weisman MH (2012) The prevalence of HLA-B27 in the US: data from the US National Health and Nutrition Examination Survey, 2009. Arthritis Rheum 64:1407–1411CrossRef Reveille JD, Hirsch R, Dillon CF, Carroll MD, Weisman MH (2012) The prevalence of HLA-B27 in the US: data from the US National Health and Nutrition Examination Survey, 2009. Arthritis Rheum 64:1407–1411CrossRef
22.
go back to reference Cortes A, Hadler J, Pointon JP, Robinson PC, Karaderi T, Leo P et al (2013) Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet 45:730–738CrossRef Cortes A, Hadler J, Pointon JP, Robinson PC, Karaderi T, Leo P et al (2013) Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet 45:730–738CrossRef
23.
go back to reference Robinson PC, Claushuis TA, Cortes A, Martin TM, Evans DM, Leo P et al (2015) Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis. Arthritis Rheumatol 67:140–151CrossRef Robinson PC, Claushuis TA, Cortes A, Martin TM, Evans DM, Leo P et al (2015) Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis. Arthritis Rheumatol 67:140–151CrossRef
24.
go back to reference Cortes A, Maksymowych WP, Wordsworth BP, Inman RD, Danoy P, Rahman P et al (2015) Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis. Ann Rheum Dis 74:1387–1393CrossRef Cortes A, Maksymowych WP, Wordsworth BP, Inman RD, Danoy P, Rahman P et al (2015) Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis. Ann Rheum Dis 74:1387–1393CrossRef
25.
go back to reference Rudwaleit M, Haibel H, Baraliakos X, Listing J, Marker-Hermann E, Zeidler H et al (2009) The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum 60:717–727CrossRef Rudwaleit M, Haibel H, Baraliakos X, Listing J, Marker-Hermann E, Zeidler H et al (2009) The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum 60:717–727CrossRef
26.
go back to reference Turina MC, Yeremenko N, van Gaalen F, van Oosterhout M, Berg IJ, Ramonda R, Lebre CM, Landewé R, Baeten D (2017) Serum inflammatory biomarkers fail to identify early axial spondyloarthritis: results from the SpondyloArthritis Caught Early (SPACE) cohort. RMD Open. doi:10.1136/rmdopen-2016-000319 CrossRef Turina MC, Yeremenko N, van Gaalen F, van Oosterhout M, Berg IJ, Ramonda R, Lebre CM, Landewé R, Baeten D (2017) Serum inflammatory biomarkers fail to identify early axial spondyloarthritis: results from the SpondyloArthritis Caught Early (SPACE) cohort. RMD Open. doi:10.​1136/​rmdopen-2016-000319 CrossRef
27.
go back to reference Poddubnyy D, Haibel H, Listing J, Märker-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 64:1388–1398CrossRef Poddubnyy D, Haibel H, Listing J, Märker-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 64:1388–1398CrossRef
28.
go back to reference Glintborg B, Ostergaard M, Krogh NS, Dreyer L, Kristensen HL, Hetland ML (2010) Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years’ surveillance in the Danish nationwide DANBIO registry. Ann Rheum Dis 69:2002–2008CrossRef Glintborg B, Ostergaard M, Krogh NS, Dreyer L, Kristensen HL, Hetland ML (2010) Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years’ surveillance in the Danish nationwide DANBIO registry. Ann Rheum Dis 69:2002–2008CrossRef
29.
go back to reference Vastesaeger N, van der Heijde D, Inman RD, Wang Y, Deodhar A et al (2011) Predicting the outcome of ankylosing spondylitis therapy. Ann Rheum Dis 70:973–981CrossRef Vastesaeger N, van der Heijde D, Inman RD, Wang Y, Deodhar A et al (2011) Predicting the outcome of ankylosing spondylitis therapy. Ann Rheum Dis 70:973–981CrossRef
30.
go back to reference Perrotta FM, Addimanda O, Ramonda R, D'Angelo S, Lubrano E, Marchesoni A, Olivieri I, Punzi L, Salvarani C, Spadaro A (2014) Predictive factors for partial remission according to the Ankylosing Spondylitis Assessment Study working group in patients with ankylosing spondylitis treated with anti-TNFα drugs. Reumatismo 66:208–214. doi:10.4081/reumatismo.2014.756 CrossRefPubMed Perrotta FM, Addimanda O, Ramonda R, D'Angelo S, Lubrano E, Marchesoni A, Olivieri I, Punzi L, Salvarani C, Spadaro A (2014) Predictive factors for partial remission according to the Ankylosing Spondylitis Assessment Study working group in patients with ankylosing spondylitis treated with anti-TNFα drugs. Reumatismo 66:208–214. doi:10.​4081/​reumatismo.​2014.​756 CrossRefPubMed
31.
go back to reference 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 randomized placebo-controlled trial (ABILITY-1). Ann Rheum Dis 72:815–822CrossRef 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 randomized placebo-controlled trial (ABILITY-1). Ann Rheum Dis 72:815–822CrossRef
32.
go back to reference Klingberg E, Nurkkala M, Carlsten H, Forsblad-d'Elia H (2014) Biomarkers of bone metabolism in ankylosing spondylitis in relation to osteoproliferation and osteoporosis. J Rheumatol 41:1349–1356CrossRef Klingberg E, Nurkkala M, Carlsten H, Forsblad-d'Elia H (2014) Biomarkers of bone metabolism in ankylosing spondylitis in relation to osteoproliferation and osteoporosis. J Rheumatol 41:1349–1356CrossRef
33.
go back to reference Appel H, Ruiz-Heiland G, Listing J, Zwerina J, Herrmann M, Mueller R, Haibel H, Baraliakos X, Hempfing A, Rudwaleit M, Sieper J, Schett G (2009) Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 60:3257–3262CrossRef Appel H, Ruiz-Heiland G, Listing J, Zwerina J, Herrmann M, Mueller R, Haibel H, Baraliakos X, Hempfing A, Rudwaleit M, Sieper J, Schett G (2009) Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 60:3257–3262CrossRef
34.
go back to reference Shi J, Ying H, Du J, Shen B (2017) Serum sclerostin levels in patients with ankylosing spondylitis and rheumatoid arthritis: a systematic review and meta-analysis. Biomed Res Int. doi:10.1155/2017/9295313 Shi J, Ying H, Du J, Shen B (2017) Serum sclerostin levels in patients with ankylosing spondylitis and rheumatoid arthritis: a systematic review and meta-analysis. Biomed Res Int. doi:10.​1155/​2017/​9295313
35.
go back to reference Mattey DL, Packham JC, Nixon NB, Coates L, Creamer P, Hailwood S, Taylor GJ, Bhalla AK (2012) Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis. Arthritis Res Ther. doi:10.1186/ar3857 CrossRef Mattey DL, Packham JC, Nixon NB, Coates L, Creamer P, Hailwood S, Taylor GJ, Bhalla AK (2012) Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis. Arthritis Res Ther. doi:10.​1186/​ar3857 CrossRef
36.
go back to reference Arends S, van der Veer E, Groen H, Houtman PM, Jansen TL, Leijsma MK et al (2011) Serum MMP-3 level as a biomarker for monitoring and predicting response to etanercept treatment in ankylosing spondylitis. J Rheumatol 38:1644–1650CrossRef Arends S, van der Veer E, Groen H, Houtman PM, Jansen TL, Leijsma MK et al (2011) Serum MMP-3 level as a biomarker for monitoring and predicting response to etanercept treatment in ankylosing spondylitis. J Rheumatol 38:1644–1650CrossRef
37.
go back to reference Keyszer G, Lambiri I, Nagel R, Keysser C, Keysser M, GromnicaIhle E et al (1999) Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers. J Rheumatol 26:251–258PubMed Keyszer G, Lambiri I, Nagel R, Keysser C, Keysser M, GromnicaIhle E et al (1999) Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers. J Rheumatol 26:251–258PubMed
38.
go back to reference Maksymowych WP, Landewé R, Conner-Spady B, Dougados M, Mielants H, van der Tempel H, Poole AR, Wang N, van der Heijde D (2007) Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis. Arthritis Rheum 56:1846–1853CrossRef Maksymowych WP, Landewé R, Conner-Spady B, Dougados M, Mielants H, van der Tempel H, Poole AR, Wang N, van der Heijde D (2007) Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis. Arthritis Rheum 56:1846–1853CrossRef
39.
40.
go back to reference Hammer HB, Kvien TK, Glennås A, Melby K (1995) A longitudinal study of calprotectin as an inflammatory marker in patients with reactive arthritis. Clin Exp Rheumatol 13:59–64PubMed Hammer HB, Kvien TK, Glennås A, Melby K (1995) A longitudinal study of calprotectin as an inflammatory marker in patients with reactive arthritis. Clin Exp Rheumatol 13:59–64PubMed
42.
go back to reference Reveille JD (2015) Biomarkers for diagnosis, monitoring of progression, and treatment responses in ankylosing spondylitis and axial spondyloarthritis. Clin Rheumatol 34:1009–1018CrossRef Reveille JD (2015) Biomarkers for diagnosis, monitoring of progression, and treatment responses in ankylosing spondylitis and axial spondyloarthritis. Clin Rheumatol 34:1009–1018CrossRef
43.
go back to reference Kim YG, Sohn DH, Zhao X, Sokolove J, Lindstrom TM, Yoo B, Lee CK, Reveille JD, Taurog JD, Robinson WH (2014) Role of protein phosphatase magnesium-dependent 1A and anti-protein phosphatase magnesium-dependent 1A autoantibodies in ankylosing spondylitis. Arthritis Rheumatol 66:2793–2803CrossRef Kim YG, Sohn DH, Zhao X, Sokolove J, Lindstrom TM, Yoo B, Lee CK, Reveille JD, Taurog JD, Robinson WH (2014) Role of protein phosphatase magnesium-dependent 1A and anti-protein phosphatase magnesium-dependent 1A autoantibodies in ankylosing spondylitis. Arthritis Rheumatol 66:2793–2803CrossRef
44.
go back to reference Baraliakos X, Baerlecken N, Witte T, Heldmann F, Braun J (2014) High prevalence of anti-CD74 antibodies specific for the HLA class II-associated invariant chain peptide (CLIP) in patients with axial spondyloarthritis. Ann Rheum Dis 73:1079–1082CrossRef Baraliakos X, Baerlecken N, Witte T, Heldmann F, Braun J (2014) High prevalence of anti-CD74 antibodies specific for the HLA class II-associated invariant chain peptide (CLIP) in patients with axial spondyloarthritis. Ann Rheum Dis 73:1079–1082CrossRef
45.
go back to reference van der Linden SM, Valkenburg HA, de Jongh BM, Cats A (1984) The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum 27:241–249CrossRef van der Linden SM, Valkenburg HA, de Jongh BM, Cats A (1984) The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum 27:241–249CrossRef
46.
go back to reference Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD (1973) Ankylosing spondylitis and HL-A 27. Lancet 1:904–907CrossRef Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD (1973) Ankylosing spondylitis and HL-A 27. Lancet 1:904–907CrossRef
48.
go back to reference Lin H, Gong YZ (2017) Association of HLA-B27 with ankylosing spondylitis and clinical features of the HLA-B27-associated ankylosing spondylitis: a meta-analysis. Rheumatol Int oi. doi:10.1007/s00296-017-3741-3742 Lin H, Gong YZ (2017) Association of HLA-B27 with ankylosing spondylitis and clinical features of the HLA-B27-associated ankylosing spondylitis: a meta-analysis. Rheumatol Int oi. doi:10.​1007/​s00296-017-3741-3742
49.
go back to reference Taurog JD, Chhabra A, Colbert RA (2016) Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med 374:2563–2574CrossRef Taurog JD, Chhabra A, Colbert RA (2016) Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med 374:2563–2574CrossRef
50.
go back to reference Tran TM, Hong S, Edwan JH, Colbert RA (2016) ERAP1 reduces accumulation of aberrant and disulfide-linked forms of HLA-B27 on the cell surface. Mol Immunol 74:10–17CrossRef Tran TM, Hong S, Edwan JH, Colbert RA (2016) ERAP1 reduces accumulation of aberrant and disulfide-linked forms of HLA-B27 on the cell surface. Mol Immunol 74:10–17CrossRef
51.
go back to reference Miossec P, Kolls JK (2012) Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov 11:763–776CrossRef Miossec P, Kolls JK (2012) Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov 11:763–776CrossRef
52.
go back to reference Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21:467–476CrossRef Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21:467–476CrossRef
53.
go back to reference Marinoni B, Ceribelli A, Massarotti MS et al (2014) The Th17 axis in psoriatic disease: pathogenetic and therapeutic implications. Auto Immun Highlights 5:9–19CrossRef Marinoni B, Ceribelli A, Massarotti MS et al (2014) The Th17 axis in psoriatic disease: pathogenetic and therapeutic implications. Auto Immun Highlights 5:9–19CrossRef
54.
go back to reference Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146CrossRef Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146CrossRef
55.
go back to reference Oppmann B, Lesley R, Blom B et al (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13:715–725CrossRef Oppmann B, Lesley R, Blom B et al (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13:715–725CrossRef
56.
go back to reference Smith JA, Colbert RA (2014) Review: the interleukin-23/interleukin-17 axis in spondyloarthritis pathogenesis: Th17 and beyond. Arthritis Rheumatol 66:231–241CrossRef Smith JA, Colbert RA (2014) Review: the interleukin-23/interleukin-17 axis in spondyloarthritis pathogenesis: Th17 and beyond. Arthritis Rheumatol 66:231–241CrossRef
57.
go back to reference Ciccia F, Ferrante A, Triolo G (2016) Intestinal dysbiosis and innate immune responses in axial spondyloarthritis. Curr Opin Rheumatol 28:352–358CrossRef Ciccia F, Ferrante A, Triolo G (2016) Intestinal dysbiosis and innate immune responses in axial spondyloarthritis. Curr Opin Rheumatol 28:352–358CrossRef
59.
go back to reference van Duivenvoorde LM, Dorris ML, Satumtira N, van Tok MN, Redlich K, Tak PP, Taurog JD, Baeten DL (2012) Relationship between inflammation, bone destruction, and osteoproliferation in the HLA-B27/human β2 -microglobulin-transgenic rat model of spondylarthritis. Arthritis Rheum 64:3210–3219CrossRef van Duivenvoorde LM, Dorris ML, Satumtira N, van Tok MN, Redlich K, Tak PP, Taurog JD, Baeten DL (2012) Relationship between inflammation, bone destruction, and osteoproliferation in the HLA-B27/human β2 -microglobulin-transgenic rat model of spondylarthritis. Arthritis Rheum 64:3210–3219CrossRef
60.
go back to reference Sieper J, Listing J, Poddubnyy D, Song IH, Hermann KG, Callhoff J, Syrbe U, Braun J, Rudwaleit M (2016) Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a randomised multicentre trial (ENRADAS). Ann Rheum Dis 75:1438–1443CrossRef Sieper J, Listing J, Poddubnyy D, Song IH, Hermann KG, Callhoff J, Syrbe U, Braun J, Rudwaleit M (2016) Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a randomised multicentre trial (ENRADAS). Ann Rheum Dis 75:1438–1443CrossRef
61.
go back to reference Spadaro A, Punzi L, Marchesoni A et al (2010) Switching from infliximab or etanercept to adalimumab in resistant or intollerant patients with spondyloarthritis: a 4-year study. Rheumatology (Oxford) 49:1107–1111. doi:10.1093/rheumatology/keq008 CrossRef Spadaro A, Punzi L, Marchesoni A et al (2010) Switching from infliximab or etanercept to adalimumab in resistant or intollerant patients with spondyloarthritis: a 4-year study. Rheumatology (Oxford) 49:1107–1111. doi:10.​1093/​rheumatology/​keq008 CrossRef
62.
go back to reference Lubrano E, Parsons WJ, Perrotta FM (2016) Assessment of response to treatment, remission, and minimal disease activity in axial psoriatic arthritis treated with tumor necrosis factor inhibitors. J Rheumatol 43:918–923. doi:10.3899/jrheum.151404 CrossRefPubMed Lubrano E, Parsons WJ, Perrotta FM (2016) Assessment of response to treatment, remission, and minimal disease activity in axial psoriatic arthritis treated with tumor necrosis factor inhibitors. J Rheumatol 43:918–923. doi:10.​3899/​jrheum.​151404 CrossRefPubMed
63.
go back to reference Spadaro A, Lubrano E, Marchesoni A et al (2013) Remission in ankylosing spondylitis treated with anti-TNF-α drugs: a national multicentre study. Rheumatology (Oxford) 52:1914–1919CrossRef Spadaro A, Lubrano E, Marchesoni A et al (2013) Remission in ankylosing spondylitis treated with anti-TNF-α drugs: a national multicentre study. Rheumatology (Oxford) 52:1914–1919CrossRef
64.
go back to reference Callhoff J, Sieper J, Weiß A, Zink A, Listing J (2015) Efficacy of TNFα blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis. Ann Rheum Dis 74:1241–1248CrossRef Callhoff J, Sieper J, Weiß A, Zink A, Listing J (2015) Efficacy of TNFα blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis. Ann Rheum Dis 74:1241–1248CrossRef
65.
go back to reference Sieper J, Kivitz A, van Tubergen A, Deodhar A, Coteur G, Woltering F, Landewé R (2015) Impact of certolizumab pegol on patient-reported outcomes in patients with axial spondyloarthritis. Arthritis Care Res (Hoboken) 67:1475–1480CrossRef Sieper J, Kivitz A, van Tubergen A, Deodhar A, Coteur G, Woltering F, Landewé R (2015) Impact of certolizumab pegol on patient-reported outcomes in patients with axial spondyloarthritis. Arthritis Care Res (Hoboken) 67:1475–1480CrossRef
66.
go back to reference van der Heijde D, Joshi A, Pangan AL, Chen N, Betts K, Mittal M, Bao Y (2016). 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) 55:80–88 van der Heijde D, Joshi A, Pangan AL, Chen N, Betts K, Mittal M, Bao Y (2016). 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) 55:80–88
67.
go back to reference Wu C, Wang S, Xian P, Yang L, Chen Y, Mo X (2016) Effect of anti-TNF antibodies on clinical response in rheumatoid arthritis patients: a meta-analysis. Biomed Res Int. doi:10.1155/2016/7185708 Wu C, Wang S, Xian P, Yang L, Chen Y, Mo X (2016) Effect of anti-TNF antibodies on clinical response in rheumatoid arthritis patients: a meta-analysis. Biomed Res Int. doi:10.​1155/​2016/​7185708
68.
go back to reference Maneiro JR, Souto A, Salgado E, Mera A, Gomez-Reino JJ (2015) Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis. RMD Open. doi:10.1136/rmdopen-2014-0000171 Maneiro JR, Souto A, Salgado E, Mera A, Gomez-Reino JJ (2015) Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis. RMD Open. doi:10.​1136/​rmdopen-2014-0000171
69.
go back to reference Ritchlin C, Rahman P, Kavanaugh A et al (2014) PSUMMIT 2 Study Group. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo controlled, randomized PSUMMIT 2 trial. Ann Rheum Dis 73:990–999CrossRef Ritchlin C, Rahman P, Kavanaugh A et al (2014) PSUMMIT 2 Study Group. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo controlled, randomized PSUMMIT 2 trial. Ann Rheum Dis 73:990–999CrossRef
70.
go back to reference Deodhar A, Gottlieb AB, Boehncke WB et al (2016) Efficacy and safety results of guselkumab, an anti-IL23 monoclonal antibody, in patients with active psoriatic arthritis over 24 weeks: a phase 2a, randomized, double-blind, placebo-controlled study. Poster session presented at ACR/ARHP Annual Meeting; 2016; Washington, DC. Deodhar A, Gottlieb AB, Boehncke WB et al (2016) Efficacy and safety results of guselkumab, an anti-IL23 monoclonal antibody, in patients with active psoriatic arthritis over 24 weeks: a phase 2a, randomized, double-blind, placebo-controlled study. Poster session presented at ACR/ARHP Annual Meeting; 2016; Washington, DC.
71.
go back to reference Poddubnyy D, Hermann KG, Callhoff J, Listing J, Sieper J (2014) 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 73:817–823CrossRef Poddubnyy D, Hermann KG, Callhoff J, Listing J, Sieper J (2014) 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 73:817–823CrossRef
72.
go back to reference Baeten D, Baraliakos X, Braun J et al (2013) Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet 382:1705–1713CrossRef Baeten D, Baraliakos X, Braun J et al (2013) Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet 382:1705–1713CrossRef
73.
go back to reference Baeten D, Sieper J, Braun J et al (2015) MEASURE 1 study group; MEASURE 2 study group. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med 373:2534–2548CrossRef Baeten D, Sieper J, Braun J et al (2015) MEASURE 1 study group; MEASURE 2 study group. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med 373:2534–2548CrossRef
74.
go back to reference Baraliakos X, Deodhar A, Braun J et al (2015) Effect of interleukin-17A inhibition on spinal radiographic changes through 2 years in patients with active ankylosing spondylitis: results of a phase 3 study with secukinumab [abstract]. Arthritis Rheumatol; 67 (suppl 10) Baraliakos X, Deodhar A, Braun J et al (2015) Effect of interleukin-17A inhibition on spinal radiographic changes through 2 years in patients with active ankylosing spondylitis: results of a phase 3 study with secukinumab [abstract]. Arthritis Rheumatol; 67 (suppl 10)
75.
go back to reference Smolen JS, Braun J, Dougados M, Emery P, Fitzgerald O, Helliwell P et al (2014) Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force. Ann Rheum Dis 73:6–16CrossRef Smolen JS, Braun J, Dougados M, Emery P, Fitzgerald O, Helliwell P et al (2014) Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force. Ann Rheum Dis 73:6–16CrossRef
76.
go back to reference Perrotta FM, Guerra G, De Socio A, Scriffignano S, Lubrano E (2017) Mesenchimal stem cells: a possible role in the pathogenesis and treatment of spondyloarthritis. Reumatismo 69:1–8CrossRef Perrotta FM, Guerra G, De Socio A, Scriffignano S, Lubrano E (2017) Mesenchimal stem cells: a possible role in the pathogenesis and treatment of spondyloarthritis. Reumatismo 69:1–8CrossRef
Metadata
Title
Unmet Needs in Axial Spondyloarthritis
Authors
Ennio Lubrano
Antonia De Socio
Fabio Massimo Perrotta
Publication date
01-12-2018
Publisher
Springer US
Published in
Clinical Reviews in Allergy & Immunology / Issue 3/2018
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-017-8637-0

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