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Abstract
Background Patients with spondyloarthritis with radiographic sacroiliitis are traditionally classified according to the modified New York (mNY) criteria as ankylosing spondylitis (AS) and more recently according to the Assessment of SpondyloArthritis international Society (ASAS) criteria as radiographic axial spondyloarthritis (r-axSpA).
Objective To investigate the agreement between the mNY criteria for AS and the ASAS criteria for r-axSpA and reasons for disagreement.
Methods Patients with back pain ≥3 months diagnosed as axSpA with radiographic sacroiliitis (mNY radiographic criterion) were selected from eight cohorts (ASAS, Esperanza, GESPIC, OASIS, Reuma.pt, SCQM, SPACE, UCSF). Subsequently, we calculated the percentage of patients who fulfilled the ASAS r-axSpA criteria within the group of patients who fulfilled the mNY criteria and vice versa in six cohorts with complete information.
Results Of the 3882 patients fulfilling the mNY criteria, 93% also fulfilled the ASAS r-axSpA criteria. Inversely, of the 3434 patients fulfilling the ASAS r-axSpA criteria, 96% also fulfilled the mNY criteria. The main cause for discrepancy between the two criteria sets was the reported age at onset of back pain.
Conclusion Almost all patients with axSpA with radiographic sacroiliitis fulfil both ASAS and mNY criteria, which supports the interchangeable use of the terms AS and r-axSpA.
- spondyloarthritis
- ankylosing spondylitis
- outcomes research
- epidemiology
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Key messages
What is already known about this subject?
Patients with spondyloarthritis with radiographic sacroiliitis can be classified using the modified New York (mNY) criteria for ankylosing spondylitis (AS) or the Assessment of SpondyloArthritis international Society (ASAS) criteria for radiographic axial spondyloarthritis (r-axSpA). However, discussion remains whether these criteria define the same patients.
What does this study add?
This study demonstrates that patients with axSpA classified as AS according to the mNY criteria and those classified as r-axSpA according to the ASAS criteria are mostly the same. These findings support the interchangeable use of the terms r-axSpA and AS.
How might this impact on clinical practice or future developments?
Acknowledging that r-axSpA and AS are interchangeable increases comparability between studies, since both terms describe the same patients (ie, patients with axSpA with radiographic sacroiliitis). This also ensures that results from older research on AS cohorts can be directly compared with more recently published articles on r-axSpA cohorts.
Background
Traditionally, patients with axial spondyloarthritis (axSpA) with definite structural changes on conventional radiographs are classified according to the modified New York (mNY) criteria as ankylosing spondylitis (AS). However, they may also be classified according to the more recent Assessment of SpondyloArthritis international Society (ASAS) axSpA criteria as radiographic axSpA (r-axSpA).
Both the mNY and the ASAS axSpA classification criteria use the radiographic criterion as defined by the mNY criteria (ie, sacroiliitis of at least grade 2 bilaterally or at least grade 3 unilaterally). However, the additionally required (clinical) features of the classification criteria differ (table 1). Importantly, patients with age at onset of back pain ≥45 years cannot fulfil the ASAS criteria, but there is no age limit for the mNY criteria.1 2 Patients without the inflammatory character of back pain fulfil the ASAS criteria if another SpA feature is present, but only fulfil the mNY criteria if there is limitation in spinal mobility. These differences in the clinical part of both criteria sets raise the question whether the two sets classify the same patients with axSpA with radiographic sacroiliitis.
The aim of this study was to investigate if patients who fulfil the mNY criteria also fulfil the ASAS criteria for r-axSpA and vice versa. The second objective was to investigate reasons for disagreement.
Methods
Patients diagnosed with axSpA who had back pain for at least 3 months and definite radiographic sacroiliitis based on local reading, according the mNY radiographic criterion (#4a or 4b in table 1) were selected from eight cohorts (ASAS, Esperanza, GErman SPondyloarthritis Inception Cohort (GESPIC), Outcome in Ankylosing Spondylitis International Study (OASIS), Reuma.pt, Swiss Clinical Quality Management (SCQM), SPondyloArthritis Caught Early cohort (SPACE) and University of California San Francisco (UCSF) axSpA cohort1 3–9). The ASAS cohort included patients with undiagnosed axSpA irrespective of symptom duration in 25 ASAS centres across 16 countries in Western Europe, Turkey, Asia, Colombia and Canada between 2005 and 2009.1 Esperanza is a Spanish national health programme for early SpA, which started inclusion in 2007.6 GESPIC started in 2000 and consists of patients with axSpA and symptom duration of up to 10 years.7 OASIS consists of Dutch, Belgian and French patients with established AS, which started in 1996.8 Since 2008, Reuma.pt started with the inclusion of Portuguese rheumatic patients of various diseases and disease stages in a national register, including patients with early and established axSpA.3 The SCQM axSpA cohort started in Switzerland in 2005 including patients with early and established disease.4 SPACE is an early chronic back pain cohort including European patients since 2009.9 Patients in the UCSF axSpA cohort started enrolling in 2007; patients with early and established disease from the UCSF clinic are included.5 Approval from the medical ethical committees was obtained per cohort, and for all patients written informed consent was obtained prior to inclusion.
For these cohorts, we calculated how many patients with SpA with radiographic sacroiliitis fulfil the mNY criteria (mNY+) and the ASAS r-axSpA criteria (ASAS+). Subsequently, we calculated the percentage of patients who fulfil the ASAS r-axSpA criteria within the group of patients who fulfil the mNY criteria. In six cohorts, we were also able to calculate the percentage of patients fulfilling the mNY criteria within the group fulfilling the ASAS r-axSpA criteria. For the Esperanza and OASIS cohorts, specific information on the individual items of the mNY clinical criteria was unavailable. Consequently, it was not possible to calculate the percentage of patients fulfilling the mNY criteria within the subgroup fulfilling the ASAS criteria. Flowcharts were used to visualise fulfilment of the criteria sets (online supplementary figure S1).
Supplemental material
For the patients with axSpA with radiographic sacroiliitis, the first step was to determine whether a patient had inflammatory back pain (IBP). For the purpose of this study, the first clinical criterion of the mNY was equated to IBP according to the ASAS definition.10 The second step was to determine the number of SpA features (<1 vs ≥1) as well as whether the patient had mobility restrictions. Mobility restrictions were defined using the age-adjusted fifth percentile scores of healthy individuals from Ramiro et al 11; if the Schober’s test and lateral spinal flexion were below the age-adjusted fifth percentile value or chest expansion was below the age-adjusted and height-adjusted fifth percentile value, mobility was considered restricted. The final step was to look at age at onset of back pain (<45 vs ≥45 years old).
Results
A total of 7636 patients with a SpA diagnosis and back pain >3 months were included in these eight cohorts. Of these, 4041 patients had a diagnosis of axSpA with radiographic sacroiliitis and were available for analysis. In total, 3882 patients fulfilled the mNY criteria, of which 3607 (93%; range 88%–100%) also fulfilled the ASAS r-axSpA criteria (figure 1A). From the six cohorts (N=3721) in which the fulfilment of the mNY criteria in the subgroup of patients fulfilling the ASAS r-axSpA criteria (N=3434) could be analysed, 3300 (96%; range 84%–98%) also fulfilled the mNY criteria (figure 1B).
Percentage of patients fulfilling ASAS r-axSpA within subgroup fulfilling mNY criteria (3607/3882) (A) and percentage of patients fulfilling mNY criteria within subgroup fulfilling ASAS r-axSpA (3300/3434) (B), per cohort and overall. ASAS, Assessment of SpondyloArthritis international Society cohort; Esperanza, Spanish national health programme for early SpA; GESPIC, GErman SPondyloarthritis Inception Cohort; mNY, modified New York; OASIS, Outcome in Ankylosing Spondylitis International Study; r-axSpA, radiographic axial spondyloarthritis; Reuma.pt, Portuguese Register for Rheumatic Diseases; SCQM, Swiss Clinical Quality Management cohort; SPACE, SPondyloArthritis Caught Early cohort; UCSF, University of California San Francisco axSpA cohort.
For all 4041 patients with r-axSpA fulfilment of the criteria sets was determined (online supplementary tables S1-S3). In total, 3607 (89%) of patients fulfilled both criteria sets; 275 (7%) only the mNY criteria; 134 (3%) only the ASAS criteria and 25 (1%) neither set (table 2).
Percentage of patients with axSpA with radiographic sacroiliitis fulfilling both sets of criteria, either criteria set or neither
The main difference between the two criteria sets was caused by the reported age at onset of back pain; 99.7% of the patients fulfilling the mNY criteria could potentially fulfil the ASAS criteria except for registered age at onset (online supplementary figure S4).
Out of the 275 mNY+patients not fulfilling the ASAS criteria (7% of all included patients), 265 (96%) cases were due to the age criterion and 10 (4%) due to the absence of SpA features including IBP (online supplementary table 1). These 10 patients had spinal mobility limitation as the only clinical feature. The 134 mNY-/ASAS+ did not have mobility restriction or IBP but another SpA feature instead. For the cohorts that had data available (N=1833), the human leucocyte antigen B27 (HLA-B27) status was determined in each of the subgroups. In the mNY+/ASAS+ group, HLA-B27 positivity was 68%. In the mNY-/ASAS+ group, a similar percentage was found (72%), whereas in the mNY+/ASAS- group this percentage was only 46%, thus only slightly higher than the mNY-/ASAS- group (42%) (online supplementary table S2).
Discussion
‘Classification criteria are standardised definitions that are primarily intended to create well-defined, relatively homogeneous cohorts of patients for clinical research; they are not intended to capture every single patient but rather to capture the majority of patients who share key features of the condition’.12 Patients with axSpA with radiographic sacroiliitis are traditionally classified according to the mNY criteria and more recently according to the ASAS criteria. The data presented in this study show that patients with axSpA classified as AS according to mNY criteria and those classified as r-axSpA according to ASAS criteria are mostly the same. Nonetheless, there is minor disagreement, mainly due to age at onset of back pain. The latter is reported by patients at the time of diagnosis in almost all cohorts and therefore susceptible to recall bias, a valid concern especially for the cohorts containing patients with a long disease duration and long gap between symptom onset and diagnosis. The age criterion was introduced with the implementation of the ASAS criteria in 2009; this was mainly based on data from Feldtkeller et al, 13 which showed that 95% of AS patients reported an age of onset <45 years. Based on this fact, one would expect around 5% of the patients fulfilling the mNY criteria not to fulfil the ASAS criteria. In this study, this percentage is 7%.
Due to the nature of the data and the slight differences between the two criteria sets some assumptions had to be made, which is a limitation to this study. The first assumption concerns IBP; in general, the ASAS definition of IBP10 was used. However, if this was unavailable (and could not be defined from individual components of IBP), the rheumatologist’s assessment as provided in the dataset was used instead. The second assumption regards mobility limitations; according to the mNY criteria, mobility limitations are to be identified based on age-adjusted and gender-adjusted comparisons; however, in the original publication no reference values were provided. Therefore, reference values resulting from the MOBILITY study11 were used. If information on mobility was unavailable, the rheumatologist’s judgement of ‘restricted mobility’ as provided in the dataset was used. Both assumptions may have influenced the proportion of patients fulfilling either of the criteria sets.
As shown in the HLA-B27 analysis, the mNY+/ASAS- group showed a lower percentage of HLA-B27 positives. HLA-B27 positivity is associated with earlier disease onset,13–15 which may explain the low percentage of HLA-B27+ in the mNY+/ASAS- group (48%) and is in line with the highest HLA-B27 positivity (72%) in the mNY-/ASAS+ group. An alternative explanation may be that patients in the mNY+/ASAS- group are misclassified as having r-axSpA as a higher HLA-B27 percentage is expected in mNY+ patients. The overall percentage of HLA-B27 found in this study is relatively low, which may be due to the local readings of the radiographs that may have resulted in false classifications for both classification sets.16
In conclusion, this study found that agreement between the mNY and ASAS r-axSpA criteria is very high, which supports the interchangeable use of the terms AS and r-axSpA. This has important implications for the axSpA research field, since older literature used mNY and AS, whereas more recent literature often uses ASAS criteria and r-axSpA. Acknowledging that both criteria sets identify the same patients implies that older literature on AS and newer literature on r-axSpA can be directly compared.
Acknowledgments
The authors thank all patients and their rheumatologists for participation in the different cohorts. For Esperanza, we would like to thank all patients participating in the Esperanza Programme as well as all members of the Esperanza Study Group. For scientific advice on the GESPIC cohort design, we thank Prof M Leirisalo-Repo, Prof D van der Heijde, and Prof M Dougados. We thank B Buss and P Tietz for monitoring the GESPIC cohort; J Callhoff, A Weiss and M Niewerth for the data management support; J Vahldiek and G Heine for the X-ray images handling and for the development of the image scoring interface and to all patients who voluntarily participated in this cohort. Further, we would like to thank all rheumatologists for inclusion of their patients in GESPIC: J Brandt, H Brandt, G-R Burmester, H Deister, E Edelmann, J Emmerich, M Enderlein, A Gauliard, E Gromnica-Ihle, F Heldmann, S Hermann, U von Hinüber, Ü Hübner, K Karberg, H Nüßlein, R Pelle-Lohfink, D Pick, G Reichmuth, E Riehers, M Rihl, R Schmidt, S Schnarr, U Schneider, I-H Song, I Spiller, U Syrbe, V Walz, S Wassenberg, H M Wisseler, S Zinke. For Reuma.pt, the authors would like to thank all the Portuguese Rheumatology centres that participate in Reuma.pt and contributed to this work. The authors would also like to acknowledge the assistance with data cleaning and analysis of M Hebeisen in the SCQM population subset. A list of rheumatology private practices and hospitals that are contributing to the SCQM registries can be found on: http://www.scqm.ch/institutions. For SPACE, the authors would like to thank the different participating centres: University of Padova, Padova, Italy (Dr R Ramonda); Diakonhjemmet Hospital, Oslo, Norway (Prof H Dagfinrud); University of Göteborg, Göteborg, Sweden (Prof LTH Jacobsson) on behalf of Swedish centres, Amsterdam UMC, Amsterdam, the Netherlands (Dr M van de Sande); Groene Hart Hospital, Gouda, the Netherlands (Dr M van Oosterhout). The initial findings of the work presented in this manuscript have been presented at the EULAR 2019 conference in Madrid and have been published in a conference abstract (OP0031 Ann Rheum Dis 2019;78(Suppl 2):85-85. doi: 10.1136/annrheumdis-2019-eular.992).
References
Footnotes
Handling editor Josef S Smolen
Contributors DvdH and SR helped in study concept and design. All authors contributed to acquisition, analysis and interpretation of data. AB, SR and DvdH wrote the manuscript. All authors critically revised the manuscript. All authors revised and approved the final manuscript to be published.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests AM reports grants and speaker/consultancy fees from AbbVie, Pfizer, BMS, UCB and Merck, outside the submitted work; DvdH reports speaker/consultancy fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB outside the submitted work and is the Director of Imaging Rheumatology bv.; EDM reports grants and speaker/consultancy fees from AbbVie, BMS, MSD, Novartis, Pfizer, Roche and UCB outside the submitted work; DP reports grants and speaker/consultancy fees from AbbVie, MSD, Novartis and Pfizer and speaker/consultancy fees from BMS, Lilly, Roche, UCB and Celgene outside the submitted work; MR reports speaker/consultancy fees from AbbVie, BMS, Celgene, Chugai, Eli-Lily, Janssen, MSD, Novartis, Pfizer and UCB outside the submitted work; AvT reports grants from Pfizer, AbbVie, UCB and Biogen and grants and speaker/consultancy fees from Novartis outside the submitted work; FAvG reports grants from MSD, Novartis, AbbVie, the Dutch Arthritis Society, Stichting Vrienden van Sole Mio, UCB and Pfizer outside the submitted work; SR reports speaker/consultancy fees from AbbVie, Eli-Lilly, Novartis and Sanofi and grants and speaker/consultancy fees from MSD outside the submitted work. AB, AC, MD, LG and MJS have nothing to disclose. GESPIC has been financially supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung—BMBF), as part of the German competence network in rheumatology (Kompetenznetz Rheuma). As funding by BMBF was reduced according to schedule in 2005 and stopped in 2007, complementary financial support has been obtained also from Abbott/Abbvie, Amgen, Centocor, Schering-Plough and Wyeth. Since 2010 GESPIC is supported by Abbvie, additional support has been obtained also from ArthroMark (grants number FKZ 01EC1401A) and METARTHROS (grant number FKZ 01EC1407A) projects funded by BMBF.
Patient consent for publication Obtained in each of the original cohorts.
Ethics approval Obtained in each of the original cohorts.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data may be obtained from a third party and are not publicly available.