Downloaded from ard.bmj.com on September 26, 2014 - Published by group.bmj.com
Letter
The concept of axial spondyloarthritis. Lessons from the INFAST study Sieper et al1 evaluated whether combination therapy with infliximab (IFX) and naproxen (NPX) was superior to treatment with NPX alone in patients who had active moderate-to-severe early (disease duration under 3 years) active axial spondyloarthritis (SpA) and who were naive to non-steroidal anti-inflammatory drugs (NSAIDs) or had only been treated with a submaximal dose of NSAIDs. This study is the first investigation of the potential benefits of early tumour necrosis factor (TNF) antagonist treatment in active axial SpA patients who are not yet refractory to NSAID therapy. Additionally, this represents the first randomised controlled clinical trial to use the imaging portion of the Assessment of SpondyloArthritis International Society criteria for axial SpA with active inflammation of the sacroiliac joints on MRI at baseline. Most importantly, the evidence from this study supports early diagnosis and treatment of SpA with a full dose of NSAIDs first, escalating to combination NSAID+TNF antagonist treatment in patients who have insufficient response. Moreover, this study provides important insights about the application of the new classification criteria for axial SpA in a clinical trial. Approximately 60% of patients had ankylosing spondylitis (AS) fulfilling the modified New York radiographic criteria. Thus, 40% of patients had non-radiographic axial SpA classified by MRI; it would be of interest to know if in these patients the additional SpA features for classification were different from AS patients. Arthritis was quite often in both treatment arms (45.3% vs 26.9%, respectively). Importantly, the 66-joint swollen joint count and 68-joint tender joint count were ameliorated considerably in both treatment arms and significantly better for swollen joints with NSAID+TNF antagonist treatment. Also in other studies testing adalimumab against placebo and etanercept against sulfasalazine, respectively, arthritis was found in 29% up to 52% of patients with early axial SpA.2–4 Evidently, simultaneous peripheral symptoms are frequent in non-radiographic and early axial SpA. This raises the question if future studies should include together patients fulfilling the axial and/or peripheral SpA criteria to establish treatment evidences for SpA in general; thus would be possible to promote approval of established and new treatments for most conditions unified under the umbrella of SpA instead of testing for each individual diagnosis and subgroup of clinical manifestations. However, this requires more attention to infections associated with reactive arthritis which have been included in the criteria for peripheral but not for axial SpA.5–7 Preceding infections (balanitis, urethritis, cervicitis and/or acute diarrhoea) are noted in 37% of patients with peripheral SpA.8 Furthermore, 35% of the patients with peripheral SpA have radiographic sacroiliitis.8 This overlap between axial and peripheral symptoms demonstrates that the construct of separating SpA into predominant clinical manifestations is somewhat artificial and only partially reflects the clinical reality given the heterogeneous character and fluctuating course of the diseases belonging to the SpA concept. Especially in the early years of the disease, the main target of the new classification criteria, AS progresses by a series of flares involving localised areas such as the knee, neck, ankle or localised area of the back.9–11 Many patients with SpA at some time of the disease can have either
Ann Rheum Dis April 2014 Vol 73 No 4
prominent peripheral and axial symptoms concurrently or peripheral and axial symptoms successively. The classification may change from axial to peripheral and vice versa at different times in a given study, compromising the consistency of classification in long-term trials. Finally, the description of increased frequency of Chlamydia-positive synovial tissue samples in patients with chronic undifferentiated SpA, the growing insight into the aetiology of persistent chlamydial infection and the promising treatment of Chlamydia-induced arthritis with combination antibiotic therapy indicate the necessity of further splitting SpA into underlying disease entities such as reactive arthritis (c.f. ref. 12). Henning Zeidler Correspondence to Professor Henning Zeidler, Emeritus, Hannover Medical School, Hannover, Germany, Wolfsburger Damm 26c, Hannover 30625, Germany; [email protected] Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed. To cite Zeidler H. Ann Rheum Dis 2014;73:e18. Received 19 November 2013 Accepted 21 November 2013 Published Online First 6 December 2013
▸ http://dx.doi.org/10.1136/annrheumdis-2013-204955 Ann Rheum Dis 2014;73:e18. doi:10.1136/annrheumdis-2013-204940
REFERENCES 1
2
3
4
5
6
7 8
9
10 11
12
Sieper J, Lenaerts J, Wollenhaupt 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 2014;73:101–7. Sieper J, van der Heijde D, Dougados M, 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;72:815–22. Haibel H, Rudwaleit M, Listing J, 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 2008;58:1981–91. Song IH, Hermann K, Haibel 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 randomized controlled trial. Ann Rheum Dis 2011;70:590–6. Rudwaleit M, van der Heijde D, Landewé R, et al. The Assessment of SpondyloArthritis International Society (ASAS) Classification Criteria for peripheral Spondyloarthritis and for Spondyloarthritis in general. Ann Rheum Dis 2011;70:15–21. Zeidler H, Amor B. The Assessment in Spondyloarthritis International Society (ASAS) classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general: the spondyloarthritis concept in progress. Ann Rheum Dis 2011;70:1–3. Zeidler H. The historical concept of interrelated conditions lumped together as a family of distinct diseases is not outdated. Arthritis Rheum 2013;65:2214–5. van den Berg R, van Gaalen F, van der Helm-van Mil A, et al. Performance of classification criteria for peripheral spondyloarthritis and psoriatic arthritis in the Leiden Early Arthritis cohort. Ann Rheum Dis 2012;71:1366–9. Wilkinson M, Bywaters EG. Clinical features and course of ankylosing spondylitis; as seen in a follow-up of 222 hospital referred cases. Ann Rheum Dis 1958;17:209–28. Brophy S, Calin A. Definition of disease flare in ankylosing spondylitis: the patients’ perspective. J Rheumatol 2002;29:954–8. Stone MA, Pomeroy E, Keat A, et al. Assessment of the impact of flares in ankylosing spondylitis disease activity using the Flare Illustration. Rheumatology 2008;47:1213–8. Zeidler H, Hudson AP. New insights into Chlamydia and arthritis. Promise of a cure? Ann Rheum Dis 2014;73:637–44.
e18
Downloaded from ard.bmj.com on September 26, 2014 - Published by group.bmj.com
The concept of axial spondyloarthritis. Lessons from the INFAST study Henning Zeidler Ann Rheum Dis 2014 73: e18 originally published online December 6, 2013
doi: 10.1136/annrheumdis-2013-204940
Updated information and services can be found at: http://ard.bmj.com/content/73/4/e18.full.html
These include:
References
This article cites 12 articles, 10 of which can be accessed free at: http://ard.bmj.com/content/73/4/e18.full.html#ref-list-1
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Letter
The concept of axial spondyloarthritis. Lessons from the INFAST study Sieper et al1 evaluated whether combination therapy with infliximab (IFX) and naproxen (NPX) was superior to treatment with NPX alone in patients who had active moderate-to-severe early (disease duration under 3 years) active axial spondyloarthritis (SpA) and who were naive to non-steroidal anti-inflammatory drugs (NSAIDs) or had only been treated with a submaximal dose of NSAIDs. This study is the first investigation of the potential benefits of early tumour necrosis factor (TNF) antagonist treatment in active axial SpA patients who are not yet refractory to NSAID therapy. Additionally, this represents the first randomised controlled clinical trial to use the imaging portion of the Assessment of SpondyloArthritis International Society criteria for axial SpA with active inflammation of the sacroiliac joints on MRI at baseline. Most importantly, the evidence from this study supports early diagnosis and treatment of SpA with a full dose of NSAIDs first, escalating to combination NSAID+TNF antagonist treatment in patients who have insufficient response. Moreover, this study provides important insights about the application of the new classification criteria for axial SpA in a clinical trial. Approximately 60% of patients had ankylosing spondylitis (AS) fulfilling the modified New York radiographic criteria. Thus, 40% of patients had non-radiographic axial SpA classified by MRI; it would be of interest to know if in these patients the additional SpA features for classification were different from AS patients. Arthritis was quite often in both treatment arms (45.3% vs 26.9%, respectively). Importantly, the 66-joint swollen joint count and 68-joint tender joint count were ameliorated considerably in both treatment arms and significantly better for swollen joints with NSAID+TNF antagonist treatment. Also in other studies testing adalimumab against placebo and etanercept against sulfasalazine, respectively, arthritis was found in 29% up to 52% of patients with early axial SpA.2–4 Evidently, simultaneous peripheral symptoms are frequent in non-radiographic and early axial SpA. This raises the question if future studies should include together patients fulfilling the axial and/or peripheral SpA criteria to establish treatment evidences for SpA in general; thus would be possible to promote approval of established and new treatments for most conditions unified under the umbrella of SpA instead of testing for each individual diagnosis and subgroup of clinical manifestations. However, this requires more attention to infections associated with reactive arthritis which have been included in the criteria for peripheral but not for axial SpA.5–7 Preceding infections (balanitis, urethritis, cervicitis and/or acute diarrhoea) are noted in 37% of patients with peripheral SpA.8 Furthermore, 35% of the patients with peripheral SpA have radiographic sacroiliitis.8 This overlap between axial and peripheral symptoms demonstrates that the construct of separating SpA into predominant clinical manifestations is somewhat artificial and only partially reflects the clinical reality given the heterogeneous character and fluctuating course of the diseases belonging to the SpA concept. Especially in the early years of the disease, the main target of the new classification criteria, AS progresses by a series of flares involving localised areas such as the knee, neck, ankle or localised area of the back.9–11 Many patients with SpA at some time of the disease can have either
Ann Rheum Dis April 2014 Vol 73 No 4
prominent peripheral and axial symptoms concurrently or peripheral and axial symptoms successively. The classification may change from axial to peripheral and vice versa at different times in a given study, compromising the consistency of classification in long-term trials. Finally, the description of increased frequency of Chlamydia-positive synovial tissue samples in patients with chronic undifferentiated SpA, the growing insight into the aetiology of persistent chlamydial infection and the promising treatment of Chlamydia-induced arthritis with combination antibiotic therapy indicate the necessity of further splitting SpA into underlying disease entities such as reactive arthritis (c.f. ref. 12). Henning Zeidler Correspondence to Professor Henning Zeidler, Emeritus, Hannover Medical School, Hannover, Germany, Wolfsburger Damm 26c, Hannover 30625, Germany; [email protected] Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed. To cite Zeidler H. Ann Rheum Dis 2014;73:e18. Received 19 November 2013 Accepted 21 November 2013 Published Online First 6 December 2013
▸ http://dx.doi.org/10.1136/annrheumdis-2013-204955 Ann Rheum Dis 2014;73:e18. doi:10.1136/annrheumdis-2013-204940
REFERENCES 1
2
3
4
5
6
7 8
9
10 11
12
Sieper J, Lenaerts J, Wollenhaupt 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 2014;73:101–7. Sieper J, van der Heijde D, Dougados M, 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;72:815–22. Haibel H, Rudwaleit M, Listing J, 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 2008;58:1981–91. Song IH, Hermann K, Haibel 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 randomized controlled trial. Ann Rheum Dis 2011;70:590–6. Rudwaleit M, van der Heijde D, Landewé R, et al. The Assessment of SpondyloArthritis International Society (ASAS) Classification Criteria for peripheral Spondyloarthritis and for Spondyloarthritis in general. Ann Rheum Dis 2011;70:15–21. Zeidler H, Amor B. The Assessment in Spondyloarthritis International Society (ASAS) classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general: the spondyloarthritis concept in progress. Ann Rheum Dis 2011;70:1–3. Zeidler H. The historical concept of interrelated conditions lumped together as a family of distinct diseases is not outdated. Arthritis Rheum 2013;65:2214–5. van den Berg R, van Gaalen F, van der Helm-van Mil A, et al. Performance of classification criteria for peripheral spondyloarthritis and psoriatic arthritis in the Leiden Early Arthritis cohort. Ann Rheum Dis 2012;71:1366–9. Wilkinson M, Bywaters EG. Clinical features and course of ankylosing spondylitis; as seen in a follow-up of 222 hospital referred cases. Ann Rheum Dis 1958;17:209–28. Brophy S, Calin A. Definition of disease flare in ankylosing spondylitis: the patients’ perspective. J Rheumatol 2002;29:954–8. Stone MA, Pomeroy E, Keat A, et al. Assessment of the impact of flares in ankylosing spondylitis disease activity using the Flare Illustration. Rheumatology 2008;47:1213–8. Zeidler H, Hudson AP. New insights into Chlamydia and arthritis. Promise of a cure? Ann Rheum Dis 2014;73:637–44.
e18
Downloaded from ard.bmj.com on September 26, 2014 - Published by group.bmj.com
The concept of axial spondyloarthritis. Lessons from the INFAST study Henning Zeidler Ann Rheum Dis 2014 73: e18 originally published online December 6, 2013
doi: 10.1136/annrheumdis-2013-204940
Updated information and services can be found at: http://ard.bmj.com/content/73/4/e18.full.html
These include:
References
This article cites 12 articles, 10 of which can be accessed free at: http://ard.bmj.com/content/73/4/e18.full.html#ref-list-1
Email alerting service
Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions
To order reprints go to: http://journals.bmj.com/cgi/reprintform
To subscribe to BMJ go to: http://group.bmj.com/subscribe/
