Progression of Nonradiographic Axial Spondyloarthritis to Ankylosing Spondylitis

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1 ARTHRITIS & RHEUMATOLOGY Vol. 68, No. 6, June 2016, pp DOI /art VC 2016, American College of Rheumatology Progression of Nonradiographic Axial Spondyloarthritis to Ankylosing Spondylitis A Population-Based Cohort Study Runsheng Wang, 1 Sherine E. Gabriel, 2 and Michael M. Ward 1 Objective. The long-term outcome of patients with nonradiographic axial spondyloarthritis (SpA) is unclear, particularly whether few or most progress to ankylosing spondylitis (AS). Our objective was to examine the progression to AS in a population-based inception cohort of patients with nonradiographic axial SpA. Methods. The Rochester Epidemiology Project (REP) is a longstanding population-based study of health in the residents of Olmsted County, Minnesota. We searched the REP from 1985 to 2010 using diagnostic and procedural codes for back pain, HLA B27, and magnetic resonance imaging of the pelvis, and we performed detailed chart reviews to identify subjects who fulfilled the Assessment of SpondyloArthritis international Society classification criteria for axial SpA but did not have AS. We followed these subjects from disease onset to March 15, 2015, and used survival analysis to measure the time to progression to AS. Results. After screening 2,151 patients, we identified 83 subjects with new-onset nonradiographic axial The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Supported in part by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH. The current study used data from the Rochester Epidemiology Project, which is supported by the NIH (National Institute on Aging award R01-AG and National Center for Advancing Translational Sciences Clinical and Translational Science Award Program grant UL1-TR ). 1 Runsheng Wang, MD, Michael M. Ward, MD, MPH: National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland; 2 Sherine E. Gabriel, MD, MSc: Mayo Clinic, Rochester, Minnesota. Address correspondence to Michael M. Ward, MD, MPH, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Building 10 CRC, Room , 10 Center Drive, Bethesda, MD wardm1@mail.nih.gov. Submitted for publication August 18, 2015; accepted in revised form December 3, SpA. Over a mean follow-up of 10.6 years, progression to AS occurred in 16 patients. The probability that the condition would remain as nonradiographic axial SpA at 5, 10, and 15 years was 93.6%, 82.7%, and 73.6%, respectively. There was more frequent and more rapid progression among subjects in the imaging arm (n 5 18) than among those in the clinical arm (n 5 65) (28% versus 17%; hazard ratio 3.50 [95% confidence interval ], P ). Conclusion. Progression to AS occurred in a minority (26%) of patients with nonradiographic axial SpA over as long as 15 years of follow-up. This suggests that the classification criteria for nonradiographic axial SpA identifies many patients in whom the condition is unlikely to progress to AS or that nonradiographic axial SpA represents a prolonged prodromal state that takes longer to evolve to AS and thus requires longer follow-up. Spondyloarthritis (SpA) is a group of inflammatory conditions that primarily affect the axial skeleton, with ankylosing spondylitis (AS) being the prototypical disease. Radiographic sacroiliitis is the key component for classification of AS by the modified New York criteria (1). However, it may take up to 10 years from the onset of clinical symptoms for radiographic sacroiliitis of this degree to develop, and delay in diagnosis and treatment may consequently occur (2,3). The condition, which is characterized by symptoms of AS but without radiographic abnormalities in sacroiliac joints, was originally reported in HLA B27 positive relatives of AS patients (4). More recently, this condition was called preradiographic spondylitis and was proposed to be a precursor stage of AS (5). To facilitate earlier identification of patients, the Assessment of SpondyloArthritis international Society (ASAS) developed new classification criteria for axial SpA which included patients with 1415

2 1416 WANG ET AL clinical features of SpA who may or may not have radiographic sacroiliitis (6). Patients can be classified as having axial SpA either by having HLA B27 and 2 clinical features of SpA (the clinical arm criteria) or by having sacroiliitis on radiographs or magnetic resonance imaging (MRI) and 1 clinical SpA feature (the imaging arm criteria) (6). Patients who fulfill the criteria for axial SpA but do not have radiographic sacroiliitis sufficiently advanced to meet the modified New York criteria have been categorized as nonradiographic axial SpA. Cohorts of patients with nonradiographic axial SpA according to the ASAS criteria have greater clinical and genetic heterogeneity than do cohorts of patients with AS, including a lower proportion of men and lower levels of systemic and spinal inflammation (3,7 9). This clinical heterogeneity has raised questions about the prognosis of patients with nonradiographic axial SpA and the degree to which the criteria identify patients who are likely to progress to AS or who may have a different outcome. This question has been addressed in two previous studies. A prospective longitudinal study reported that 11.6% of 95 patients with nonradiographic axial SpA had progression to AS in 2 years, whereas a population-based study of 20 patients reported that 20% had progression in 8 years (10,11). It remains unclear what proportion of patients with nonradiographic axial SpA have progression to AS and over what time frame. In addition, the long-term prognosis of patients in the clinical arm of nonradiographic axial SpA has been questioned because in the absence of sacroiliitis on imaging, some patients with fibromyalgia or mechanical back pain could be included (12). Cross-sectional studies have reported that patients in the clinical arm and those in the imaging arm were similar in terms of most clinical features, disease activity, and disease severity (13,14). However, the likelihood of progression to AS in patients in these 2 arms has not been compared. Furthermore, the lower proportion of men with nonradiographic axial SpA compared to AS has suggested that male sex may be a risk factor for radiographic progression, but this has not been examined in longitudinal studies (3,8). To address these questions, a population-based longitudinal study in which patients are followed up for years is needed, given that the development of radiographic sacroiliitis is slow. The Rochester Epidemiology Project (REP) is a unique medical linkage system, with access to the medical records of the population of Olmsted County, Minnesota, and detailed recording of diagnoses, tests, and procedures since 1966 (15). In 2000 and 2010, 98% of Olmsted County residents, including 90, ,000 adults, agreed to participate in the REP (15). The REP is therefore ideal for population-based studies requiring long-term follow-up. Using the REP, we conducted a retrospective study in which we identified an inception cohort of patients with nonradiographic axial SpA and examined their progression to AS. PATIENTS AND METHODS Subject inclusion and exclusion criteria. We sought to identify an inception cohort of patients with nonradiographic axial SpA. Inclusion criteria were as follows: enrollment in the REP, occurrence of new-onset back pain at ages years that lasted more than 3 months and occurred between January 1, 1985 and December 31, 2010, and meeting the ASAS criteria for axial SpA, for either the imaging arm or the clinical arm (6). In addition, for the clinical arm, subjects were required to have at least 1 radiograph that did not show sacroiliitis within 2 years before or at any time after documentation of the occurrence of the second SpA feature. Subjects who had radiographic sacroiliitis within 2 years before and after positive findings on MRI were excluded from the imaging arm. We gave precedence to MRI evidence of sacroiliitis, and therefore, subjects who satisfied criteria for both arms were included in the imaging arm. We excluded subjects who had back pain lasting,3 months, isolated neck pain, or physician visits for chronic back pain before This study was approved by the institutional review boards of the Mayo Clinic and Olmsted Medical Center. Case ascertainment. To identify subjects who fulfilled criteria for the imaging arm, we searched for Olmsted County residents who had an MRI of the pelvis at ages years during the period between January 1, 1997 and December 31, We screened the MRI reports for sacroiliitis. Reports showing active sacroiliitis, osteitis, bone marrow edema, or inflammatory lesions were considered positive, and MRI images were then reviewed by a rheumatologist (MMW) to confirm the presence of active sacroiliitis based on the ASAS criteria (6). Pelvis MRIs were rarely available in the REP prior to 1997, so we did not extend our search to an earlier date. To identify subjects who fulfilled the clinical arm criteria, we searched for Olmsted County residents who met the inclusion criteria and had a procedural or diagnostic code for HLA B27 testing. Among the patients who were identified as possibly having nonradiographic axial SpA based on the research codes in the REP, we then performed a detailed review of the full medical records of those who had either active sacroiliitis on MRI or HLA B27 plus chronic back pain. Clinical information, including back pain characteristics, SpA features, radiographic and MRI reports, and medications, was collected through March 15, 2015 to determine their eligibility and outcomes. SpA features were defined as described in the ASAS handbook (6). For inflammatory back pain, we used any of 3 criteria sets (Calin et al, Berlin, or ASAS) that were commonly used during the years of this study, or we used the treating rheumatologist s determination. All subsequent and available radiographs of the pelvis, hips, lumbar spine, or abdomen were reviewed, and radiographic sacroiliitis was graded according to the modified New York criteria by a rheumatologist (MMW) who was

3 PROGNOSIS OF NONRADIOGRAPHIC AXIAL SpA 1417 blinded with regard to the clinical information. The intrareader reliability was tested on 25 randomly selected radiographs scored several days apart and was found to be high (k for specific grade and k for meeting/not meeting the modified New York criteria). If films were unavailable, we judged whether the modified New York criteria were met based on the descriptions in the radiology reports. Statistical analysis. We used survival analysis, with Kaplan-Meier curves and the log rank test, to measure time to progression to AS. For subjects in the imaging arm, time 0 was defined as the date of the first pelvis MRI demonstrating active sacroiliitis. For subjects in the clinical arm, time 0 was defined as the date when the second clinical SpA feature was recorded by a physician. AS was defined by the presence of bilateral grade 2 or unilateral grade 3 or grade 4 sacroiliitis on radiographs (1). The end point for analysis was the date of the first film demonstrating radiographic sacroiliitis of this degree. Subjects who did not have radiographic sacroiliitis of this degree during follow-up and had a clinic visit after March 15, 2013, were considered not to have had progression to AS, and those whose last clinic visit was before March 15, 2013, were considered to be lost to follow-up. Subjects who died, were lost to follow-up, or had no events during the follow-up period were censored on the date of death or the last clinic visit. In a sensitivity analysis, we used the date of the last negative radiograph as the time of censoring. Sex differences were compared using the t-test, Fisher s exact test, and Wilcoxon s rank sum test, as appropriate. We used R programs (version 3.0.1) (R Foundation for Statistical Computing) for all analyses. RESULTS Study cohort. We identified 1,142 Olmsted County residents who had a pelvis MRI at ages years during the period between 1997 and 2010 (Figure 1). Most Figure 1. Flow chart showing the process of inclusion and exclusion of study subjects. Shaded boxes represent patients who were included in the nonradiographic axial spondyloarthritis (SpA) cohort. In the clinical arm, subjects who did not have any radiograph within 2 years before or at any time after documentation of the occurrence of the second SpA feature (22, 1) were excluded. MRI 5 magnetic resonance imaging; CPT 5 Current Procedural Terminology; ICD-9 5 International Classification of Diseases, Ninth Revision; HICDA 5 Hospital International Classification of Disease Adaptation of the ICD-8 for hospital morbidity; ASAS 5 Assessment of SpondyloArthritis international Society.

4 1418 WANG ET AL Table 1. cohort* Demographic and clinical features of 83 subjects included in the nonradiographic axial SpA Total (n 5 83) Imaging arm (n 5 18) Clinical arm (n 5 65) Age at inclusion, mean 6 SD years Age at back pain onset, mean 6 SD years Duration of follow-up, mean 6 SD years Male, % HLA B27 positive, % Uveitis, % Arthritis, % Dactylitis, % Enthesitis, % History of psoriasis, % History of IBD, % History of reactive arthritis, % History of IBP, % History of smoking, % Family history of SpA, % Good response to NSAIDs, % Elevated levels of markers of inflammation, % Methotrexate, ever taken, % Sulfasalazine, ever taken, % TNFi, ever taken, % No. of follow-up radiographs after inclusion, median (range) 1 (0 7) 1 (0 4) 1 (0 7) * SpA 5 spondyloarthritis; IBD 5 inflammatory bowel disease; IBP 5 inflammatory back pain; NSAIDs 5 nonsteroidal antiinflammatory drugs; TNFi 5 tumor necrosis factor inhibitor. The remainder were HLA B27 negative or unknown. studies were ordered for investigation of abdominal or gynecologic symptoms rather than musculoskeletal complaints. After review, we identified 26 subjects who had an MRI of the pelvis that showed active sacroiliitis. All of the pelvis MRIs that were included were performed under a dedicated sacroiliitis protocol, except in 1 patient with inflammatory bowel disease, which was performed for gastrointestinal reasons. We identified 1,009 Olmsted County residents who had a clinic visit for back pain at ages years during the period between 1985 and 2010 and who underwent testing for HLA B27 (Figure 1). Of these, 168 subjects were HLA B27 positive, among whom 136 had back pain for more than 3 months. After detailed medical record review and application of inclusion and exclusion criteria, a total of 83 subjects with new-onset nonradiographic axial SpA were identified. Figure 2. Kaplan-Meier curves for the progression from nonradiographic axial spondyloarthritis (SpA) to ankylosing spondylitis. A, Entire cohort (solid line), with 95% confidence interval (shaded area). B, Patients in the imaging arm and the clinical arm. The x-axes represent years of follow-up; the y-axes represent the proportion remaining as nonradiographic axial SpA. Numbers across the bottom are the number of subjects at risk at each time point.

5 PROGNOSIS OF NONRADIOGRAPHIC AXIAL SpA 1419 Figure 3. Kaplan-Meier curves for the progression from nonradiographic axial spondyloarthritis (SpA) to ankylosing spondylitis, using the last radiograph with negative findings as the time of censoring. A, Entire cohort (solid line), with 95% confidence interval (shaded area). B, Patients in the imaging arm and the clinical arm. The x-axes represent years of follow-up; the y-axes represent the proportion remaining as nonradiographic axial SpA. Numbers across the bottom are the number of subjects at risk at each time point. Eighteen subjects were included in the imaging arm and 65 subjects were included in the clinical arm (6 of whom had a negative pelvis MRI and 59 of whom did not have a pelvis MRI). Their demographic and clinical features are presented in Table 1. The mean 6 SD age at inclusion was years. The mean 6 SD follow-up in the entire cohort was years, with a significantly shorter period in the imaging arm than in the clinical arm ( years versus years; P, ). Subjects in the clinical arm had 0 7 followup radiographs (median 1), whereas those in the imaging arm had 0 4 (median 1). Progression to AS. At the end of follow-up, progression to AS had occurred in 16 subjects (median time to progression 5.9 years [range years]). In 54 subjects (65%), the condition remained as nonradiographic axial SpA without progression; 11 subjects (13%) were censored because of loss to follow-up, and 2 subjects (2.4%) were censored because of death. The probability that the condition would remain as nonradiographic axial SpA at 5, 10, and 15 years was 93.6% (95% confidence interval [95% CI] ), 82.7% (95% CI ), and 73.6% (95% CI ), respectively (Figure 2A). Progression to AS was significantly more frequent and faster among subjects in the imaging arm (28%; median time to AS 4.8 years) than among those in the clinical arm (17%; median time to AS 6.8 years), with a hazard ratio of 3.50 (95% CI ; P ) (Figure 2B). Because the pelvic radiographs were performed for clinical care rather than by protocol, we could have underestimated the development of radiographic sacroiliitis. To assess this potential, we did a sensitivity analysis using the date of the last negative radiograph as the time of censoring. The probability of remaining as nonradiographic axial SpA at 5, 10, and 15 years was 89.6% (95% CI ), 70.4% (95% CI ), and 53.9% (95% CI ), respectively (Figure 3A). Again, the development of radiographic sacroiliitis was significantly more frequent and faster in subjects in the imaging arm than in those in the clinical arm (P ) (Figure 3B). Sex associations. There were 44 men and 39 women in the study cohort. The men tended to be younger than the women ( years versus years; P ) and were more likely to be smokers (43% versus 26%; P ). More women than men had ever been treated with methotrexate (36% versus 18%; P ). The men had fewer follow-up radiographs (median 1 [range 0 4]) than did the women (median 1 [range 0 7]; P ). Sex was not associated with radiographic progression. Twenty-three percent of the men experienced progression, with a median time to AS of 5.9 years, while 15% of women experienced progression, with a median time to AS of 6.3 years (hazard ratio 1.58 [95% CI ], P ). No significant difference in the progression rates between men and women was seen in the sensitivity analysis (P ) (data not shown.) DISCUSSION Since the introduction of the ASAS criteria for axial SpA, there has been considerable interest in

6 1420 WANG ET AL whether patients identified as having nonradiographic axial SpA represent a group with early AS or a group with a different etiology and prognosis (7). Few studies have examined the prognosis of these patients. In the German Spondyloarthropathy Inception Cohort (GESPIC), 11.6% of 95 patients with nonradiographic axial SpA had progression to AS in 2 years (10). A small population-based study from Norway reported that 20% of subjects with nonradiographic axial SpA developed radiographic sacroiliitis in 8 years (11). Older studies that examined patients with undifferentiated SpA or possible AS, rather than those meeting the new ASAS criteria, reported that 24 42% of patients had progression to AS over a period of 5 10 years (16 18). Low-grade radiographic sacroiliitis, HLA B27, and buttock pain were prognostic factors for progression to AS in those studies (17,18). Comparisons among these studies are difficult because they included patients in different segments of the SpA spectrum. Additionally, the studies were limited by losses to follow-up of more than 40% of patients. Because the patient populations were from rheumatology clinics, the studies likely overestimated the progression to AS. Our population-based analysis addressed many of these limitations in a cohort with a larger sample, longer follow-up, and low rate of loss to follow-up. In our cohort, the probability of progressing to AS after 15 years was 26%. Our study is the first to compare the prognosis of patients in a clinical arm and in an imaging arm of nonradiographic axial SpA. We found that subjects in the imaging arm were 3.5 times more likely to have progression to AS than those in the clinical arm. This finding suggests an important difference among the entities included in the nonradiographic axial SpA umbrella, one of which is much closer to preradiographic AS while the other represents a condition with a different prognosis. Previous studies have also identified MRI evidence of sacroiliitis as a marker of progression to AS (19). Cross-sectional studies of the Spondyloarthritis Caught Early (SPACE) cohort and the Devenir des Spondylarthropathies Indiffererenciees Recentes (DESIR) cohort reported no major differences between patients in the 2 arms in terms of most clinical features, disease activity, and disease severity, although patients in the imaging arm were more likely to be male, younger, and to have a longer disease duration, no family history of SpA, and higher C-reactive protein levels (13,14). Although clinical features may be similar between the 2 arms, our results indicate that the prognosis of these patients differs substantially. In several cross-sectional studies comparing patients with nonradiographic axial SpA to patients with AS, a notable finding has been a higher proportion of men with AS as compared to nonradiographic axial SpA (3,8,9,14). Men were also found to have a higher likelihood of sacroiliitis on MRI (20). Therefore, male sex was proposed as a risk factor for radiographic progression. While we found a trend toward more frequent progression to AS in men, the difference was not statistically significant, which is likely due in part to the size of our sample. Our study has some limitations, mainly because of its retrospective design. Given the slow rate of progression to AS, only this study design was practical. First, the radiographs were taken for clinical indications, and we may have therefore underestimated the development of radiographic sacroiliitis. The end point was determined by the timing of a positive radiograph, rather than the natural progression of the condition. Not all subjects in the imaging arm had subsequent radiographs to document the development of radiographic sacroiliitis. Most subjects in the clinical arm had additional films if they had persistent symptoms, or they had no further investigations if their symptoms resolved. To investigate the impact of these actions on our estimates of progression to AS, we performed the sensitivity analysis using the date of the last negative plain films as the time of censoring. The frequency of true progression is estimated to be between that in the main analysis and that in the sensitivity analysis. Second, HLA B27 testing and pelvis MRI were not universally obtained in patients with new-onset chronic back pain, but rather, were ordered based on diagnostic needs. Similarly, some clinical features were not always explicitly documented in the clinical notes, such as the response to NSAIDs or the family history. We might therefore have omitted some patients who would have been included if this information had been available. It is difficult to predict how this might bias the results, if at all. Third, in a few subjects with early symptoms for whom radiographs were not available, we based the presence of radiographic sacroiliitis on the radiologists reports. Because radiologists are more likely to underreport than to over-report radiographic sacroiliitis, we may have underestimated the progression to AS in this small group of subjects. In conclusion, in our population-based inception cohort of patients with nonradiographic axial SpA according to the ASAS criteria, 26% developed radiographic sacroiliitis after 15 years of follow-up. Significantly more subjects in the imaging arm than in the clinical

7 PROGNOSIS OF NONRADIOGRAPHIC AXIAL SpA 1421 arm experienced progression. Our results suggest either that the classification criteria for nonradiographic axial SpA identifies many patients who are unlikely to progress to AS or that nonradiographic axial SpA is a prolonged prodromal state, with a longer evolution to AS, requiring longer follow-up time. Some researchers, after careful review of the available evidence, have raised concerns about the performance of the ASAS criteria and have proposed steps to improve their validity (21,22). Further longitudinal studies are needed to evaluate the clinical, laboratory, and radiologic features with high predictive value for progression to AS. AUTHOR CONTRIBUTIONS All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Ward had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design. Wang, Ward. Acquisition of data. Wang, Gabriel, Ward. Analysis and interpretation of data. Wang, Ward. REFERENCES 1. Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum 1984;27: Feldtkeller E, Khan MA, van der Heijde D, van der Linden S, Braun J. Age at disease onset and diagnosis delay in HLA-B27 negative versus positive patients with ankylosing spondylitis. Rheumatol Int 2003;23: Rudwaleit M, Haibel H, Baraliakos X, Listing J, Marker-Hermann E, Zeidler H, et al. The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum 2009;60: Khan MA, van der Linden SM, Kushner I, Valkenburg HA, Cats A. Spondylitic disease without radiologic evidence of sacroiliitis in relatives of HLA B27 positive ankylosing spondylitis patients. Arthritis Rheum 1985;28: Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum 2005;52: Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, Burgos- Vargas R, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis 2009;68 Suppl2:ii Robinson PC, Wordsworth BP, Reveille JD, Brown MA. Axial spondyloarthritis: a new disease entity, not necessarily early ankylosing spondylitis. Ann Rheum Dis 2013;72: Kiltz U, Baraliakos X, Karakostas P, Igelmann M, Kalthoff L, Klink C, et al. Do patients with non-radiographic axial spondylarthritis differ from patients with ankylosing spondylitis? Arthritis Care Res (Hoboken) 2012;64: Malaviya AN, Kalyani A, Rawat R, Gogia SB. Comparison of patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axspa) from a single rheumatology clinic in New Delhi. Int J Rheum Dis 2015;18: Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Marker-Hermann E, Zeidler H, et al. Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis. Ann Rheum Dis 2011;70: Bakland G, Alsing R, Singh K, Nossent JC. Assessment of SpondyloArthritis International Society criteria for axial spondyloarthritis in chronic back pain patients with a high prevalence of HLA B27. Arthritis Care Res (Hoboken) 2013;65: Deodhar A, Reveille JD, van den Bosch F, Braun J, Burgos- Vargas R, Caplan L, 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 2014;66: Van den Berg R, de Hooge M, van Gaalen F, Reijnierse M, Huizinga T, van der Heijde D. Percentage of patients with spondyloarthritis in patients referred because of chronic back pain and performance of classification criteria: experience from the Spondyloarthritis Caught Early (SPACE) cohort [published erratum appears in Rheumatology (Oxford) 2015;54:1336]. Rheumatology (Oxford) 2013;52: Molto A, Paternotte S, van der Heijde D, Claudepierre P, Rudwaleit M, Dougados M. 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 2015;74: St Sauver JL, Grossardt BR, Yawn BP, Melton LJ III, Pankratz JJ, Brue SM, et al. Data resource profile: the Rochester Epidemiology Project (REP) medical records-linkage system. Int J Epidemiol 2012;41: Mau W, Zeidler H, Mau R, Majewski A, Freyschmidt J, Stangel W, et al. Clinical features and prognosis of patients with possible ankylosing spondylitis: results of a 10-year followup. J Rheumatol 1988;15: Huerta-Sil G, Casasola-Vargas JC, Londono JD, Rivas-Ruiz R, Chavez J, Pacheco-Tena C, et al. Low grade radiographic sacroiliitis as prognostic factor in patients with undifferentiated spondyloarthritis fulfilling diagnostic criteria for ankylosing spondylitis throughout follow up. Ann Rheum Dis 2006;65: Sampaio-Barros PD, Bortoluzzo AB, Conde RA, Costallat LT, Samara AM, Bertolo MB. Undifferentiated spondyloarthritis: a longterm followup. J Rheumatol 2010;37: Bennett AN, McGonagle D, O Connor P, Hensor EM, Sivera F, Coates LC, et al. Severity of baseline magnetic resonance imaging evident sacroiliitis and HLA B27 status in early inflammatory back pain predict radiographically evident ankylosing spondylitis at eight years. Arthritis Rheum 2008;58: Van Onna M, Jurik AG, van der Heijde D, van Tubergen A, Heuft-Dorenbosch L, Landewe R. HLA-B27 and gender independently determine the likelihood of a positive MRI of the sacroiliac joints in patients with early inflammatory back pain: a 2-year MRI follow-up study. Ann Rheum Dis 2011;70: Akkoc N, Khan MA. Looking into the new ASAS classification criteria for axial spondyloarthritis through the other side of the glass. Curr Rheumatol Rep 2015;17: Van der Linden S, Akkoc N, Brown MA, Robinson PC, Khan MA. The ASAS criteria for axial spondyloarthritis: strengths, weaknesses, and proposals for a way forward. Curr Rheumatol Rep 2015;17:62.