Ankylosing spondylitis (AS) is a chronic inflammatory disorder that is part of a spectrum of diseases known as seronegative spondyloarthropathies. The disease is characterized by spinal inflammation and structural damage from osteoproliferation (1,2). The prevalence of AS has been reported to be from 0.1% to 1.4% (3) globally, and 0.2% to 0.5% (4) in the United States. AS typically affects the axial skeleton and sacroiliac joints and can lead to spinal deformity, functional disability, and significant pain and stiffness (2). However, studies have shown that 25% to 70% of patients have involvement of the hips, knees, or other joints (5,6). Moreover, spinal deformities causing sagittal imbalance can affect knee flexion, which can lead to worsened disability as well as increase joint pain (7).
Management of AS revolves around symptom relief, maintenance of function, and prevention of complications, such as contractures (8,9). Pharmacologic therapies for AS include non-steroidal anti-inflammatory drugs (NSAIDs), other analgesics, sulfasalazine, and anti-tumor necrosis factor α (TNFα) agents (10). The TNFα inhibitors have led to decreased disease activity and improved functional capacity in AS patients (11). The American College of Rheumatology guidelines recommend that adults who have active AS should initially be treated with NSAIDs and exercise, and then progress to TNFα inhibitors if the initial treatment fails. Additionally, the use of slow-acting anti-rheumatic drugs (SAARDs) and locally administered parenteral glucocorticoids have been recommended in AS patients who have active peripheral arthritis (8). Despite the pharmacological efforts, joint involvement may become progressively disabling and painful, ultimately necessitating surgical intervention (7).
Total knee arthroplasty (TKA) has been proven to be effective at improving pain in AS patients (12). Yet, despite TKA being known as an effective management technique for patients with AS, it remains unclear whether or not the annual rates of TKA in AS patients have been affected. Therefore, the purpose of this study was to evaluate AS patients who underwent TKA using a large national administrative database. Specifically, we examined the annual trends of TKA in AS patients. Specifically, we evaluated: (I) the annual trends of TKAs due to AS in the United States population; (II) the annual trends in the proportion of TKAs due to AS in the United States.
The Nationwide Inpatient Sample (NIS) was reviewed from 2002 to 2013. The NIS database provides the largest all-payer database of inpatient hospital admissions in the United States. A stratified sample of approximately 8 million records is collected annually by the database, which is part of the Healthcare Cost and Utilization Project (13). Data includes demographics, insurance type, International Classification of Diseases, Ninth Revision (ICD-9) diagnosis and procedure codes, admission and discharge data, and total charges (14). The NIS database is publically available and contains de-identified data, therefore, this study was deemed exempt by the Institutional Review Board.
All patients who underwent a primary TKA, defined by the ICD-9 procedure code 81.54, performed between January 1, 2002 and December 31, 2013 were identified (n=6,492,873). Then, to create a cohort of AS patients who underwent TKA, all TKA patients who had a diagnosis of AS, defined by the ICD-9 diagnosis code 720.0, were identified.
The incidences of TKAs due to AS were obtained by dividing the number of TKAs due to AS by the annual US population, obtained from the census bureau. The proportion of TKAs due to AS was also evaluated for each year by dividing the number of TKAs due to AS by the total number of TKAs.
Poisson regression analysis was used to analyze whether there was an annual increase in the incidence of the TKAs due to AS in the United States population, due to the count nature of the dependent variable. The United States population was used as an offset term in the regression model. The changes in the incidence of TKAs are represented using incidence rate ratios (IRRs), with IRR >1 denoting an increase in the procedural volume. Linear regression analyses were used to study the annual changes in the proportion of TKAs due to AS. The annual change in the proportion of TKAs due to AS is denoted by the regression coefficient (slope). A P value of less than 0.05 was used as the threshold for statistical significance. The 95% confidence intervals were calculated for the different measures used in the study. All of the data were analyzed with SPSS version 23 (IBM Corporation, Armonk, New York, USA). All figures were developed using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA).
During the study period, 2,986 patients who had AS who underwent TKA were identified. The annual number of TKAs with a diagnosis of AS increased by 168% from 125 to 335 (Figure 1). After normalizing to the US population, the incidence of TKAs with AS increased from 0.58 to 1.38 TKAs per million US adults [IRR =1.08 (95% CI: 1.07–1.09), P<0.001] (Figure 2).
Out of the 350,122 TKAs in 2002, 125 (0.04%) were due to AS, whereas, out of the 640,695 TKAs in 2013, 335 (0.05%) were due to AS. The prevalence of AS in those who underwent TKA increased from 2002 to 2013 [coefficient =0.002 (95% CI: 0.001–0.003), P=0.004] (Figure 3) .
Prevalence estimates of AS in the United States have been reported to range from 13.1 to 31.9 per 10,000 persons (15,16). The mainstay of treatment for AS has been medical management, with NSAIDs and exercise being considered first-line therapy (8). Since the approval of TNFα inhibitors for the management of AS, studies have confirmed their efficacy in improving clinical outcomes, functionality, and disease activity (8,11). However, it remains uncertain as to whether TNFα inhibitors slow disease progression. While TNFα inhibitors have been recommended for AS in the setting of active disease or when NSAIDs fail to work, TNFα inhibitors have yet to be established as a first-line therapy (8). On the other hand, NSAIDs have been shown to both improve pain and stiffness in both axial and non-axial disease, and to slow radiographic disease progression (17-19). Worsening joint pain and disability that has not responded to non-surgical treatment in AS patients is a major indication for arthroplasty (7). In evaluating the yearly trends of AS patients who underwent TKA, the present study found that there was a significant increase in the TKA prevalence between 2002 and 2013.
This study had limitations that were worth mentioning. A large administrative database was utilized as the primary source of data collection, which can be subject to errors at the data entry level. The most common criticism with the use of such databases relates to the accuracy of diagnosis and procedural codes (20-22). However, use of administrative data sets have proven to be valuable, and it was shown that the combination usage of diagnostic codes with procedural codes enhances the validity and reliability of the data (23), which is how the data was used in the present study. Another potential limitation of this study is that the NIS database does not provide specific data in regards to disease activity levels or medication types; therefore, this data could not be extracted from the database. As a result, we were not able to determine if certain pharmacologic regimens affected TKA trends. However, a survey study by Zochling et al. (24) reported on 1,080 AS patients who had a mean age of 50 years (range, 21–86 years), and found that 78% of patients were regularly taking NSAIDs 12 months prior to the survey. Despite these limitations, the authors of this study believe the findings are accurate and provide valuable insight into the recent TKA trends in AS patients.
The most commonly reported orthopedic procedure performed in AS patients has been total hip arthroplasty, followed by spinal osteotomies (25). Despite the prevalence of knee involvement in AS reaching as high as 70%, the literature reporting on this is limited (5,6). A recent study by Mertelsmann-Voss et al. (26) evaluated 3,825 patients who had spondyloarthritis (SpA) and had a mean age of 57 years and found that the trends in rates of TKA significantly increased over the 14-year period, from 2.7 TKAs per 100,000 persons per year in 1991 to 2.9 TKAs per 100,000 persons per year in 2005 (P<0.001). The authors additionally showed that patients who did not have inflammatory arthritis also had an increase in the trends of TKA from 49.1 per 100,000 persons per year in 1991 to 134.4 per 100,000 persons per year in 2005 (P<0.001).
There is a paucity of literature available addressing arthroplasty trends in patients who had AS and this is the first study to analyze TKA trends in the AS population. However, the literature has shown that NSAIDs (18) and potentially TNFα inhibitors (27), slow progression of bone disease in AS; however, this did not support the results of the present study, which showed a significant increase in TKA trends in AS patients between 2002 and 2013.
In conclusion, the present study evaluated the annual trends of AS patients who underwent TKA, which demonstrated an increase in TKA trends during the study period. Longer observational studies should assess TKA trends in AS patients with stratification of the data by current medical management and age. This data would allow for the analysis of TKA trends in AS patients based on the medical regimen they are receiving and also determine the age trends in those who received TKA, which in the setting of an increasing trend would also indicate success in medical therapy as TKA is being delayed. In order to truly determine the effectiveness of the AS medical therapy guidelines, disease progression must be analyzed.
Conflicts of Interest: MA Mont: AAOS, Cymedica, DJ Orthopaedics, Johnson & Johnson, Journal of Arthroplasty, Journal of Knee Surgery, Microport, National Institutes of Health (NIAMS & NICHD), Ongoing Care Solutions, Orthopedics, Orthosensor, Pacira, Peerwell, Performance Dynamics Inc., Sage, Stryker: IP royalties, Surgical Techniques International, TissueGene. JW Barrington: Biome, DJ Orthopaedics, Iconacy, Mallinckrodt, Pacira, Professional Communications, Inc. Smith & Nephew, Tier 1 Healthcare and Education Research, Zimmer. CB Paulino: DePuy, A Johnson & Johnson CompanyEthicon. M Chughtai: DJ Orthopaedics, Sage Products, Stryker. The other authors have no conflicts of interest to declare.
Ethical Statement: The NIS database is publically available and contains de-identified data, therefore, this study was deemed exempt by the Institutional Review Board.
- Wanders A, Landewé R, Dougados M, et al. Association between radiographic damage of the spine and spinal mobility for individual patients with ankylosing spondylitis: can assessment of spinal mobility be a proxy for radiographic evaluation? Ann Rheum Dis 2005;64:988-94. [Crossref] [PubMed]
- Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007;369:1379-90. [Crossref] [PubMed]
- Akkoc N. Are Spondyloarthropathies as common as rheumatoid arthritis worldwide? A review. Curr Rheumatol Rep 2008;10:371-8. [Crossref] [PubMed]
- Reveille JD. Epidemiology of spondyloarthritis in North America. Am J Med Sci 2011;341:284-6. [Crossref] [PubMed]
- Kim TJ, Kim TH. Clinical spectrum of ankylosing spondylitis in Korea. Joint Bone Spine 2010;77:235-40. [Crossref] [PubMed]
- Malaviya AN, Agrawal N, Patil NS. Clinical characteristics of peripheral spondyloarthritis without psoriasis, inflammatory enteropathy or preceding infection, from a single rheumatology clinic in northern India. Clin Rheumatol 2017;36:2613-8. [Crossref] [PubMed]
- Goodman SM, Figgie M. Lower extremity arthroplasty in patients with inflammatory arthritis: preoperative and perioperative management. J Am Acad Orthop Surg 2013;21:355-63. [PubMed]
- Ward MM, Deodhar A, Akl EA, 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 2016;68:282-98. [Crossref] [PubMed]
- van der Heijde D, Ramiro S, Landewé R, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 2017;76:978-91.
- Gordon A, Matar HE, Wilkinson JM. Hip and Knee Arthroplasty in the Patient with Inflammatory Arthritis. In: Arthroplasty-Update. Rijeka: InTech, 2013:261-90.
- Callhoff J, Sieper J, Weiß A, et al. Efficacy of TNFα blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis. Ann Rheum Dis 2015;74:1241-8. [Crossref] [PubMed]
- Parvizi J, Duffy GP, Trousdale RT. Total knee arthroplasty in patients with ankylosing spondylitis. J Bone Joint Surg Am 2001;83-A:1312-6. [Crossref] [PubMed]
- HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization Project (HCUP). 2013. Agency for Healthcare Research and Quality, Rockville, MD. Available online: https://www.hcup-us.ahrq.gov/nisoverview.jsp
- Steiner C, Elixhauser A, Schnaier J. The healthcare cost and utilization project: an overview. Eff Clin Pract 2002;5:143-51. [PubMed]
- Mikkelsen WM, Dodge HJ, Duff IF, et al. Estimates of the prevalence of rheumatic diseases in the population of Tecumseh, Michigan, 1959-60. J Chronic Dis 1967;20:351-69. [Crossref] [PubMed]
- Carter ET, McKenna CH, Brian DD, et al. Epidemiology of Ankylosing spondylitis in Rochester, Minnesota, 1935-1973. Arthritis Rheum 1979;22:365-70. [Crossref] [PubMed]
- Zochling J, van der Heijde D, Dougados M, et al. Current evidence for the management of ankylosing spondylitis: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Ann Rheum Dis 2006;65:423-32. [Crossref] [PubMed]
- Wanders A. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: A randomized clinical trial. Arthritis Rheum 2005;52:1756-65. [Crossref] [PubMed]
- Song IH, Poddubnyy DA, Rudwaleit M, et al. Benefits and risks of ankylosing spondylitis treatment with nonsteroidal antiinflammatory drugs. Arthritis Rheum 2008;58:929-38. [Crossref] [PubMed]
- van Walraven C, Bennett C, Forster AJ. Administrative database research infrequently used validated diagnostic or procedural codes. J Clin Epidemiol 2011;64:1054-9. [Crossref] [PubMed]
- Johnson EK, Nelson CP. Utility and pitfalls in the use of administrative databases for outcomes assessment. J Urol 2013;190:17-8. [Crossref] [PubMed]
- George J, Newman JM, Ramanathan D, et al. Administrative databases can yield false conclusions-an example of obesity in total joint arthroplasty. J Arthroplasty 2017;32:S86-90. [Crossref] [PubMed]
- Tanpowpong P, Broder-Fingert S, Obuch JC, et al. Multicenter study on the value of ICD-9-CM codes for case identification of celiac disease. Ann Epidemiol 2013;23:136-42. [Crossref] [PubMed]
- Zochling J, Bohl-Bühler MH, Baraliakos X, et al. Nonsteroidal anti-inflammatory drug use in ankylosing spondylitis--a population-based survey. Clin Rheumatol 2006;25:794-800. [Crossref] [PubMed]
- Kubiak EN, Moskovich R, Errico TJ, et al. Orthopaedic management of ankylosing spondylitis. J Am Acad Orthop Surg 2005;13:267-78. [Crossref] [PubMed]
- Mertelsmann-Voss C, Lyman S, Pan TJ, et al. US trends in rates of arthroplasty for inflammatory arthritis including rheumatoid arthritis, juvenile idiopathic arthritis, and spondyloarthritis. Arthritis Rheumatol 2014;66:1432-9. [Crossref] [PubMed]
- Haroon N, Inman RD, Learch TJ, et al. The impact of tumor necrosis factor α inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum 2013;65:2645-54. [PubMed]