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07-04-2016 | Spondyloarthropathies | Review | Article

New evidence on the management of spondyloarthritis

Journal: Nature Reviews Rheumatology

Authors: Joachim Sieper, Denis Poddubnyy

Authors: Joachim Sieper, Denis Poddubnyy

Publisher: Nature Publishing Group UK

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for patients with symptomatic axial spondyloarthritis (SpA), who seem to respond best if treated early in the course of disease. The effect of NSAIDs on radiographic disease progression is less clear. Conventional disease-modifying antirheumatic drugs (DMARDs) are not recommended in the treatment of axial SpA, either alone or in combination with TNF blockers. Patients with nonradiographic axial SpA (nr-axSpA) seem to respond as well to TNF blockers as do patients with radiographic axial SpA (ankylosing spondylitis (AS)). However, patients with nr-axSpA should, in addition to a high severity of symptoms, also have objective signs of inflammation, detectable by MRI or by C-reactive protein testing, to be treated with TNF blockers. Whether early TNF-blocker treatment can retard new bone formation needs clarification. In clinical trials, anti-IL-17 agents and TNF blockers showed similar efficacy in patients with AS. The potential of IL-23 blockade for treatment of axial SpA needs to be further investigated. Treatment options for peripheral SpA have been much less thoroughly investigated than those for axial SpA. However, some data indicate that TNF blockers are effective for treating peripheral arthritis, enthesitis and dactylitis, the typical manifestations of peripheral SpA.

Nat Rev Rheumatol 2016;12:282–295. doi:10.1038/nrrheum.2016.42

Literature
1.
Rudwaleit, M. et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann. Rheum. Dis. 68, 777–783 (2009).PubMed
2.
Rudwaleit, M. et al. The Assessment of SpondyloArthritis international Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann. Rheum. Dis. 70, 25–31 (2011).PubMed
3.
Sieper, J. et al. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann. Rheum. Dis. 68, 784–788 (2009).PubMed
4.
van der Linden, S., Valkenburg, H. A. & Cats, A. Evaluation of diagnostic criteria for ankylosing spondylitis. Arthritis Rheum. 27, 361–368 (1984).PubMed
5.
Carter, J. D. et al. Chlamydiae as etiologic agents in chronic undifferentiated spondylarthritis. Arthritis Rheum. 60, 1311–1316 (2009).PubMedPubMedCentral
6.
Van Praet, L. et al. Degree of bone marrow oedema in sacroiliac joints of patients with axial spondyloarthritis is linked to gut inflammation and male sex: results from the GIANT cohort. Ann. Rheum. Dis. 73, 1186–1189 (2014).PubMed
7.
Sieper, J. Developments in therapies for spondyloarthritis. Nat. Rev. Rheumatol. 8, 280–287 (2012).PubMed
8.
Zochling, J. et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann. Rheum. Dis. 65, 442–452 (2006).PubMed
9.
Braun, J. et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann. Rheum. Dis. 70, 896–904 (2011).PubMed
10.
Ward, M. M. 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. 68, 282–298 (2016).PubMed
11.
van der Heijde, D. et al. 2010 update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis. Ann. Rheum. Dis. 70, 905–908 (2011).PubMed
12.
Smolen, J. S. et al. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force. Ann. Rheum. Dis. 73, 6–16 (2014).PubMed
13.
Dougados, M. et al. Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug. Arthritis Rheum. 44, 180–185 (2001).PubMed
14.
Dougados, M. et al. Ximoprofen in ankylosing spondylitis: a double blind placebo controlled dose ranging study. Scand. J. Rheumatol. 23, 243–248 (1994).PubMed
15.
Sieper, J. 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. 67, 323–329 (2008).PubMed
16.
van der Heijde, D. et al. Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: results of a fifty-two-week, randomized, controlled study. Arthritis Rheum. 52, 1205–1215 (2005).PubMed
17.
Barkhuizen, A. et al. Celecoxib is efficacious and well tolerated in treating signs and symptoms of ankylosing spondylitis. J. Rheumatol. 33, 1805–1812 (2006).PubMed
18.
Sieper, J. 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. 73, 101–107 (2014).PubMed
19.
Anderson, J. J., Baron, G., van der Heijde, D., Felson, D. T. & Dougados, M. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum. 44, 1876–1886 (2001).PubMed
20.
Sieper, J. et al. Maintenance of biologic-free remission with naproxen or no treatment in patients with early, active axial spondyloarthritis: results from a 6-month, randomised, open-label follow-up study, INFAST Part 2. Ann. Rheum. Dis. 73, 108–113 (2014).PubMed
21.
Kroon, F. P. et al. Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis). Cochrane Database Syst. Rev. 7, CD010952 (2015).
22.
Wang, R., Dasgupta, A. & Ward, M. M. Comparative efficacy of non-steroidal anti-inflammatory drugs in ankylosing spondylitis: a Bayesian network meta-analysis of clinical trials. Ann. Rheum. Dis. (2015).
23.
Coxib and traditional NSAID Trialists' (CNT) Collaboration et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 382, 769–779 (2013).
24.
Song, I. H., Poddubnyy, D. A., Rudwaleit, M. & Sieper, J. Benefits and risks of ankylosing spondylitis treatment with nonsteroidal antiinflammatory drugs. Arthritis Rheum. 58, 929–938 (2008).PubMed
25.
Bakland, G., Gran, J. T. & Nossent, J. C. Increased mortality in ankylosing spondylitis is related to disease activity. Ann. Rheum. Dis. 70, 1921–1925 (2011).PubMed
26.
Haroon, N. N., Paterson, J. M., Li, P., Inman, R. D. & Haroon, N. Patients with ankylosing spondylitis have increased cardiovascular and cerebrovascular mortality: a population-based study. Ann. Intern. Med. 163, 409–416 (2015).PubMed
27.
Dougados, M. et al. Evaluation of the nonsteroidal anti-inflammatory drug-sparing effect of etanercept in axial spondyloarthritis: results of the multicenter, randomized, double-blind, placebo-controlled SPARSE study. Arthritis Res. Ther. 16, 481 (2014).PubMedPubMedCentral
28.
Molto, A. et al. Brief report: nonsteroidal antiinflammatory drug-sparing effect of tumor necrosis factor inhibitors in early axial spondyloarthritis: results from the DESIR cohort. Arthritis Rheumatol. 67, 2363–2368 (2015).PubMed
29.
Haibel, H. et al. No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial. Ann. Rheum. Dis. 66, 419–421 (2007).PubMed
30.
Chen, J., Lin, S. & Liu, C. Sulfasalazine for ankylosing spondylitis. Cochrane Database Syst. Rev. 11, CD004800 (2014).
31.
Haibel, H., Rudwaleit, M., Braun, J. & Sieper, J. Six months open label trial of leflunomide in active ankylosing spondylitis. Ann. Rheum. Dis. 64, 124–126 (2005).PubMedPubMedCentral
32.
Braun, J. et al. Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis: a randomized, double-blind trial. Arthritis Rheum. 63, 1543–1551 (2011).PubMed
33.
Song, I. H. 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. 70, 590–596 (2011).PubMed
34.
Braun, J. et al. Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial. Ann. Rheum. Dis. 65, 1147–1153 (2006).PubMedPubMedCentral
35.
Vincent, F. B. et al. Antidrug antibodies (ADAb) to tumour necrosis factor (TNF)-specific neutralising agents in chronic inflammatory diseases: a real issue, a clinical perspective. Ann. Rheum. Dis. 72, 165–178 (2013).PubMed
36.
Breban, M. 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. 58, 88–97 (2008).PubMed
37.
Braun, J., Baraliakos, X., Kudrin, A., Kim, H. U. & Lee, S. J. Striking discrepancy in the development of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in response to infliximab (INF) and its biosimilar CT-P13. Presented at the 2014 ACR/ARHP Annual Meeting (2014).
38.
Heiberg, M. S. et al. The comparative one-year performance of anti-tumor necrosis factor α drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: results from a longitudinal, observational, multicenter study. Arthritis Rheum. 59, 234–240 (2008).PubMed
39.
Lie, E. et al. 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, 970–978 (2015).PubMed
40.
Maksymowych, W. P. et al. A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug-refractory ankylosing spondylitis. Arthritis Rheum. 46, 766–773 (2002).PubMed
41.
Haibel, H. et al. Efficacy of oral prednisolone in active ankylosing spondylitis: results of a double-blind, randomised, placebo-controlled short-term trial. Ann. Rheum. Dis. 73, 243–246 (2014).PubMed
42.
Braun, J. et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 359, 1187–1193 (2002).PubMed
43.
van der Heijde, D. et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum. 52, 582–591 (2005).PubMed
44.
Davis, J. C. et al. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum. 48, 3230–3236 (2003).PubMed
45.
Davis, J. C. et al. Sustained durability and tolerability of etanercept in ankylosing spondylitis for 96 weeks. Ann. Rheum. Dis. 64, 1557–1562 (2005).PubMedPubMedCentral
46.
van der Heijde, D. et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 54, 2136–2146 (2006).PubMed
47.
Inman, R. D. 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. 58, 3402–3412 (2008).PubMed
48.
Landewe, R. 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. 73, 39–47 (2014).PubMed
49.
Haibel, H. et al. Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two. Arthritis Rheum. 58, 1981–1991 (2008).PubMed
50.
Barkham, N. et al. Clinical and imaging efficacy of infliximab in HLA-B27-positive patients with magnetic resonance imaging-determined early sacroiliitis. Arthritis Rheum. 60, 946–954 (2009).PubMed
51.
Sieper, J. 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. 72, 815–822 (2013).PubMed
52.
Dougados, M. 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. 66, 2091–2102 (2014).PubMed
53.
Sieper, J. et al. A randomized, double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 67, 2702–2712 (2015).PubMedPubMedCentral
54.
Machado, P. et al. Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores. Ann. Rheum. Dis. 70, 47–53 (2010).PubMed
55.
Deodhar, A. 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. 66, 2649–2656 (2014).PubMed
56.
Poddubnyy, D., Haibel, H., Braun, J., Rudwaleit, M. & Sieper, J. Brief report: clinical course over two years in patients with early nonradiographic axial spondyloarthritis and patients with ankylosing spondylitis not treated with tumor necrosis factor blockers: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheumatol. 67, 2369–2375 (2015).PubMed
57.
Haibel, H. et al. Long-term efficacy of adalimumab after drug withdrawal and retreatment in patients with active non-radiographically evident axial spondyloarthritis who experience a flare. Arthritis Rheum. 65, 2211–2213 (2013).PubMed
58.
Song, I. H. et al. Frequency and duration of drug-free remission after 1 year of treatment with etanercept versus sulfasalazine in early axial spondyloarthritis: 2 year data of the ESTHER trial. Ann. Rheum. Dis. 71, 1212–1215 (2012).PubMed
59.
US National Library of Science. ClinicalTrials.gov [online], (2016).
60.
US National Library of Science. ClinicalTrials.gov [online], (2016).
61.
US National Library of Science. ClinicalTrials.gov [online], (2016).
62.
Sieper, J. et al. Effect of certolizumab pegol over ninety-six weeks in patients with axial spondyloarthritis: results from a phase III randomized trial. Arthritis Rheumatol. 67, 668–677 (2015).PubMedPubMedCentral
63.
Rudwaleit, M. et al. MRI in predicting a major clinical response to anti-tumour necrosis factor treatment in ankylosing spondylitis. Ann. Rheum. Dis. 67, 1276–1281 (2008).PubMed
64.
Molto, A., Paternotte, S., Claudepierre, P., Breban, M. & Dougados, M. Effectiveness of tumor necrosis factor α blockers in early axial spondyloarthritis: data from the DESIR cohort. Arthritis Rheumatol. 66, 1734–1744 (2014).PubMed
65.
Ciurea, A. et al. Tumor necrosis factor α inhibition in radiographic and nonradiographic axial spondyloarthritis: results from a large observational cohort. Arthritis Rheum. 65, 3096–3106 (2013).PubMed
66.
Haibel, H., Rudwaleit, M., Listing, J. & Sieper, J. Open label trial of anakinra in active ankylosing spondylitis over 24 weeks. Ann. Rheum. Dis. 64, 296–298 (2005).PubMed
67.
Song, I. H. et al. Treatment of active ankylosing spondylitis with abatacept: an open-label, 24-week pilot study. Ann. Rheum. Dis. 70, 1108–1110 (2011).PubMed
68.
Song, I. H. 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. 62, 1290–1297 (2010).PubMed
69.
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. 73, 95–100 (2014).PubMed
70.
Sieper, J. et al. Sarilumab for the treatment of ankylosing spondylitis: results of a phase II, randomised, double-blind, placebo-controlled study (ALIGN). Ann. Rheum. Dis. 74, 1051–1057 (2015).PubMed
71.
Nam, J. L. et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann. Rheum. Dis. 73, 516–528 (2014).PubMed
72.
Langley, R. G. et al. Secukinumab in plaque psoriasis — results of two phase 3 trials. N. Engl. J. Med. 371, 326–338 (2014).PubMed
73.
Gordon, K. B. et al. A phase 2 trial of guselkumab versus adalimumab for plaque psoriasis. N. Engl. J. Med. 373, 136–144 (2015).PubMed
74.
Papp, K. et al. Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br. J. Dermatol. 173, 930–939 (2015).PubMed
75.
Leonardi, C. L. et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 371, 1665–1674 (2008).PubMed
76.
Papp, K. A. et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 371, 1675–1684 (2008).PubMed
77.
McInnes, I. B. et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 382, 780–789 (2013).PubMed
78.
Mease, P. J. et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N. Engl. J. Med. 373, 1329–1339 (2015).PubMed
79.
Baeten, D. et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet 382, 1705–1713 (2013).PubMed
80.
Baeten, D. et al. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N. Engl. J. Med. 373, 2534–2548 (2015).PubMed
81.
Sieper, J. et al. Secukinumab, a monoclonal antibody to interleukin-17A, significantly improves signs and symptoms of active ankylosing spondylitis: results of a phase 3, randomized, placebo-controlled trial with subcutaneous loading and maintenance dosing. Arthritis Rheum. 66, S232 (2014).
82.
Baeten, D. et al. Secukinumab, a monoclonal antibody to interleukin-17A, significantly improves signs and symptoms of active ankylosing spondylitis: results of a 52-week phase 3 randomized placebo-controlled trial with intravenous loading and subcutaneous maintenance dosing. Arthritis Rheum. 66 (Suppl.), S360 (2014).
83.
Poddubnyy, D., Hermann, K. G., 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. 73, 817–823 (2014).PubMed
84.
US National Library of Science. ClinicalTrials.gov [online], (2016).
85.
US National Library of Science. ClinicalTrials.gov [online], (2016).
86.
US National Library of Science. ClinicalTrials.gov [online], (2016).
87.
US National Library of Science. ClinicalTrials.gov [online], (2016).
88.
van der Heijde, D. et al. Tofacitinib in patients with ankylosing spondylitis: a phase 2, 16-week, randomized, placebo-controlled, dose-ranging study [abstract]. Arthritis Rheumatol. 67 (Suppl. 10), 5L (2015).
89.
Sandborn, W. J. et al. Ustekinumab induction and maintenance therapy in refractory Crohn's disease. N. Engl. J. Med. 367, 1519–1528 (2012).PubMed
90.
Hueber, W. 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 61, 1693–1700 (2012).PubMed
91.
Genovese, M. C. et al. Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study. Ann. Rheum. Dis. 72, 863–869 (2013).PubMed
92.
Smolen, J. et al. A phase 2 study evaluating the efficacy and safety of subcutaneously administered ustekinumab and guselkumab in patients with active rheumatoid arthritis despite treatment with methotrexate. Ann. Rheum. Dis. 74 (Suppl. 2), 76 (2015).
93.
Poddubnyy, D. et al. Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis. Ann. Rheum. Dis. 70, 1369–1374 (2011).PubMed
94.
Poddubnyy, D. et al. Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis. Arthritis Rheum. 64, 1388–1398 (2012).PubMed
95.
Ramiro, S. et al. Higher disease activity leads to more structural damage in the spine in ankylosing spondylitis: 12-year longitudinal data from the OASIS cohort. Ann. Rheum. Dis. 73, 1455–1461 (2014).PubMed
96.
Sieper, J., Appel, H., Braun, J. & Rudwaleit, M. Critical appraisal of assessment of structural damage in ankylosing spondylitis: implications for treatment outcomes. Arthritis Rheum. 58, 649–656 (2008).PubMed
97.
Boersma, J. W. Retardation of ossification of the lumbar vertebral column in ankylosing spondylitis by means of phenylbutazone. Scand. J. Rheumatol. 5, 60–64 (1976).PubMed
98.
Wanders, A. et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum. 52, 1756–1765 (2005).PubMed
99.
Kroon, F., Landewe, R., Dougados, M. & van der Heijde, D. Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis. Ann. Rheum. Dis. 71, 1623–1629 (2012).PubMed
100.
Poddubnyy, D. et al. Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort. Ann. Rheum. Dis. 71, 1616–1622 (2012).PubMed
101.
Sieper, J. et al. 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. http://​dx.​doi.​org/​10.​1136/​annrheumdis-2015-207897 (2015).
102.
van der Heijde, D. et al. Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum. 58, 3063–3070 (2008).PubMed
103.
van der Heijde, D. et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum. 58, 1324–1331 (2008).PubMed
104.
van der Heijde, D. 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. 11, R127 (2009).PubMedPubMedCentral
105.
Braun, J. et al. The effect of two golimumab doses on radiographic progression in ankylosing spondylitis: results through 4 years of the GO-RAISE trial. Ann. Rheum. Dis. 73, 1107–1113 (2014).PubMed
106.
Baraliakos, X., Haibel, H., Listing, J., Sieper, J. & Braun, J. 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, 710–715 (2014).PubMed
107.
Haroon, N. et al. The impact of tumor necrosis factor α inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum. 65, 2645–2654 (2013).PubMedPubMedCentral
108.
Baraliakos, X. et al. 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), 6L (2015).
109.
Gossec, L. et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann. Rheum. Dis. http://​dx.​doi.​org/​10.​1136/​annrheumdis-2015-208337 (2015).
110.
Coates, L. C. et al. Group for research and assessment of psoriasis and psoriatic arthritis: treatment recommendations for psoriatic arthritis 2015. Arthritis Rheumatol. http://​dx.​doi.​org/​10.​1002/​art.​39573 (2016).
111.
Dougados, M. et al. A randomised, multicentre, double-blind, placebo-controlled trial of etanercept in adults with refractory heel enthesitis in spondyloarthritis: the HEEL trial. Ann. Rheum. Dis. 69, 1430–1435 (2010).PubMed
112.
Paramarta, J. E. et al. Efficacy and safety of adalimumab for the treatment of peripheral arthritis in spondyloarthritis patients without ankylosing spondylitis or psoriatic arthritis. Ann. Rheum. Dis. 72, 1793–1799 (2013).PubMed
113.
Mease, P. et al. Randomized controlled trial of adalimumab in patients with nonpsoriatic peripheral spondyloarthritis. Arthritis Rheumatol. 67, 914–923 (2015).PubMedPubMedCentral
114.
Brown, M. A. et al. SAT0258 baseline MRI/CRP as predictors of response to etanercept in the management of patients with non-radiographic axial spondyloarthritis. Ann. Rheum. Dis. 74 (Suppl. 2), 752 (2015).