Predictors of longterm outcome in ankylosing spondylitis

OBJECTIVE: To determine predictors of longterm outcome in ankylosing spondylitis (AS). METHODS: Data were collected retrospectively on constitutional and environmental factors that may predict outcome in AS in 311 patients (252 men, 81%). Univariate statistics and multivariable linear regression analyses were used to identify factors correlated with disease outcome, which was defined in terms of radiological (Bath AS Radiology Index, BASRI) and functional status (Bath AS Functional Index, BASFI). RESULTS: Disease duration, sex, and iritis are independently associated with BASRI and account for 23% (p < 0.001) of variation in radiological scores (BASRI-t), a measure that includes the hip joint in the score. Radiological hip involvement is significantly associated with higher scores of spinal radiological change (BASRI-s) (p < 0.001). Cigarette smoking, radiological status, and Bath AS Disease Activity Index score (BASDAI) are independently associated with and account for 50% of variability in functional status (p < 0.001). CONCLUSION: Much of the variability in disease severity in AS remains unexplained. All but one of the factors associated with outcome in this study are inherent. This suggests that genetic factors have a greater influence than environmental factors on radiological progression and disability in AS. It may, however, be possible to improve longterm functional outcome in AS by targeting high risk individuals early in the disease course with more aggressive management strategies and encouraging smoking cessation in all patients with AS.     

Clinical aspects, outcome assessment, and management of ankylosing spondylitis and postenteric reactive arthritis

The cause of ankylosing spondylitis remains unclear. Proof that this disorder is an autoimmune disease attributable to crossreactivity between bacteria and HLA-B27 is still lacking. Differences in endogenous peptide presentation by HLA-B27 subtypes might be relevant in the etiopathogenesis. Fractures of the osteoporotic spine contribute to morbidity. Spinal cord injury may occur. MR imaging enables identifying sacroiliitis earlier than plain radiography. Sweet syndrome has now been described in patients with ankylosing spondylitis and Crohn disease. Progress has been made in the assessment of ankylosing spondylitis. There are now core sets for different settings and validated instruments for functioning and disease activity that will enable demonstrating efficacy of new therapeutic interventions.The debate continues on classification of postinfectious and reactive arthritis. Bacterial antigens may be found in the inflamed joints; occasionally 16S ribosomal RNA is also demonstrated. Antibiotics seem not to be effective in postenteric reactive arthritis.More than 25 years have now elapsed since the association between ankylosing spondylitis and HLA-B27 was first described in 1973. The cause of this disease is still unknown, but a lot of progress has been made regarding the molecular structure of HLA-B27, the spectrum of disease, the clinical and radiographic assessment of ankylosing spondylitis, and its treatment. Recent advances in research on ankylosing spondylitis are reviewed here.     

The assessment of ankylosing spondylitis in clinical practice

Ankylosing Spondylitis (AS) is a chronic inflammatory arthritis that predominantly affects the axial skeleton in adolescent patients causing spinal pain and stiffness. There is a marked delay, on average 8 years, between onset of disease symptoms and clinical diagnosis. The distinction between the symptoms of mechanical and inflammatory back pain remains one of the main contributing factors for the delay in diagnosis. Several classification criteria exist to aid the diagnosis of AS, but their accuracy is poor. The Ankylosing Spondylitis Assessment Study group (ASAS) has defined a core set of domains for clinical outcome measurement in AS in order to assess the disease process in individual patients and to identify those with rapidly progressive disease. New therapies, such as the tumor necrosis factor (TNF) inhibitors, have transformed the treatment paradigm in AS, especially for those patients with aggressive disease. Thus, the definition of both patient selection criteria for these agents and the development of clinical methods to assess response to therapy have become a priority. This Review focuses on measuring the degree of disease activity, function and damage in patients with AS in an ambulatory care setting, and the assessment of suitability of various outcome measures for monitoring response to treatment with TNF inhibitors.     

Plain radiographs as an outcome measure in ankylosing spondylitis

Radiographic evidence of sacroiliitis is a prerequisite for classification according to the (modified) New York criteria. Structural damage is also an important endpoint in the assessment of ankylosing spondylitis (AS). However, little research has been done on the development, validation, and application of scoring methods for radiographic changes in AS. Methodological issues that can be addressed concerning radiographic scoring methods are discussed in detail. A short introduction to the available scoring methods is presented.     

New light on uveitis in ankylosing spondylitis

Inflammatory eye disease is well recognized in ankylosing spondylitis (AS) but the relationship between the uveitis and the spondyloarthropathy is poorly defined. The following conclusions may be drawn from a study of 1331 consecutive patients with AS: the prevalence of uveitis was 40% (535 subjects), almost half of whom had greater than 5 attacks. Family studies of sib pairs, concordant for AS, showed that uveitis occurred randomly with a concordance for uveitis/no uveitis of only 43%. A comparison of patients with (n = 535) and without (n = 796) uveitis showed no important differences. Analysis of potential trigger factors among 72 patients with recurrent disease revealed no seasonal, infective or other correlation. The removal of an intrauterine device from a woman with severe intractable bilateral uveitis was associated with remission of the eye disease. In summary, although genetic background determines susceptibility to uveitis the pattern of the disease suggests the possibility of random environmental triggers unrelated to the course of the underlying rheumatological disorder.     

Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis

OBJECTIVE: To develop criteria for symptomatic improvement in patients with ankylosing spondylitis (AS), using outcome domain data from placebo-controlled clinical trials of nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: Patient data from 5 short-term, randomized, controlled trials were used to assess equivalence, reliability, and responsiveness of multiple items in the 5 outcome domains for AS treatment: physical function, pain, spinal mobility, patient global assessment, and inflammation. At least one measure per domain was responsive (standardized response mean of > 0.5), except for the spinal mobility domain, which was omitted from the criteria. We developed and tested candidate improvement criteria in a random two-thirds subset from the 3 largest trials and used the remaining one-third for validation. These 3 largest trials included 923 patients (631 receiving NSAIDs, 292 in placebo groups). We selected the multiple domain definition that best distinguished NSAID treatment from placebo by chi-square test and that had a placebo response rate of < or = 25%. RESULTS: Candidate definitions were changes in single domains and in multiple measure indices, as well as combinations of improvements in multiple domains. Worsening in a domain was defined as a change for the worse of > or = 20% and a net change for the worse of > or = 10 units on a scale of 0-100. Partial remission (for comparison purposes) was defined as an end-of-trial value of < 20/100 in each of the 4 domains. Among 20 candidate criteria, change of > or = 20% and > or = 10 units in each of 3 domains and absence of worsening in the fourth discriminated best in the development subset (51% of patients improved with NSAIDs, 25% with placebo; chi2 = 36.4, P < 0.001). Results were confirmed in the validation subset. Almost all patients satisfying the definition of partial disease remission at the end of the trial had also improved by this criterion. Among all 923 patients, improvement rates using this criterion were 49% for NSAID-treated patients and 24% for placebo-treated patients. CONCLUSION: Although further validation using data from new trials is still needed, we conclude that we have developed a clinically valid, easy-to-use measure of short-term improvement in AS.     

New pathogenetic aspects of ankylosing spondylitis

Ankylosing spondylitis is one of the oldest diseases in humans; however, it is still one of the most fascinating and mysterious in human pathology. The unusual combination of both fundamental pathological processes: inflammation and ossification (which are mostly independent in respect to time and place) is unique. Until 1973, ankylosing spondylitis did not attract much immunological research. After the detection of an association between HLA B27 and the disease, clinical and immunological research was stimulated. It was supposed that HLA B27 may be a pathogenic factor. Meanwhile, it has become well known that HLA B27 itself is not required for development of the disease; however, discovery of immunological cross-reactivity between HLA B27 and some Klebsiella antigens inspired pathogenic considerations. It is discussed that the structural similarities between enteric bacteria and HLA B27 induce autoantibodies, or that HLA B27 plays a role in antigen recognition. Possibly, HLA B27 may also act as a receptor for infectious agents and their products. Fascinating, but controversely discussed is the hypothesis that bacterial products modify the B27 molecule and, in this way, trigger the disease. All present theories about pathogenesis of ankylosing spondylitis are unsatisfactory, because many important questions cannot be answered. There are no explanations for the unusual affinity of possible pathogenic immune reactions to the spine and other organs, the induction of ossification, the merging of cartilage, or the development of sacroilitis. Especially, we do not know the important bridge (if one exists) between inflammation and ossification. The typical ossification of the spine is of dramatic consequence for the patient in respect to function and mobility.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relevance of osteoproliferation as an outcome parameter in ankylosing spondylitis

In light of the impressive efficacy of tumor necrosis factor blockers in the treatment of ankylosing spondylitis, particularly in patients with short disease duration, defining outcome parameters to monitor the structural damage of the disease has become more pertinent. In this Viewpoint the authors explore the relevance of osteoproliferation amongst other outcome parameters.     

Neurological complications of ankylosing spondylitis: neurophysiological assessment

Studies examined the neurological involvement of ankylosing spondylitis (AS) are limited. This study aimed to assess the frequency of myelopathy, radiculopathy and myopathy in AS correlating them to the clinical, radiological and laboratory parameters. Included were 24 patients with AS. Axial status was assessed using bath ankylosing spondylitis metrology index (BASMI). Patients underwent (a) standard cervical and lumbar spine and sacroiliac joint radiography, (b) somatosensory (SSEP) and magnetic motor (MEP) evoked potentials of upper and lower limbs, (c) electromyography (EMG) of trapezius and supraspinatus muscles. Patients’ mean age and duration of illness were 36 and 5.99 years. Bath ankylosing spondylitis metrology index mean score was 4.6. Twenty-five percent (n = 6) of patients had neurological manifestations, 8.3% of them had myelopathy and 16.7% had radiculopathy. Ossification of the posterior (OPLL) and anterior (OALL) longitudinal ligaments were found in 8.3% (n = 2) and 4.2% (n = 1). About 70.8% (n = 17) had ≥1 neurophysiological test abnormalities. Twelve patients (50%) had SSEP abnormalities, seven had prolonged central conduction time (CCT) of median and/or ulnar nerves suggesting cervical myelopathy. Six had delayed peripheral or root latencies at Erb’s or interpeak latency (Erb’s-C5) suggesting radiculopathy. Motor evoked potentials was abnormal in 54% (n = 13). Twelve (50%) and five (20.8%) patients had abnormal MEP of upper limbs and lower limbs, respectively. About 50% (n = 12) had myopathic features of trapezius and supraspinatus muscles. Only 8.3% (n = 2) had neuropathic features. We concluded that subclinical neurological complications are frequent in AS compared to clinically manifest complications. Somatosensory evoked potential and MEP are useful to identify AS patients prone to develop neurological complications.     

Total hip arthroplasty in ankylosing spondylitis: outcome in 340 patients

OBJECTIVE: The longterm outcome of total hip arthroplasty (THA) in ankylosing spondylitis (AS) remains unclear. Concern has been expressed regarding joint survival, given that recipients are young and active. We present outcome data on 340 THA after a mean followup of 14 years. METHODS: The 6.7% of patients (n = 309: 237 contactable) who had undergone THA were identified from our database of 4569 subjects. Responses were received from 166 subjects (112 men, 54 women, M:F = 2:1) who were assessed for employment status and outcome [i.e., pain, mobility, satisfaction, disease activity (BASDAI), function (BASFI), and global well being (BAS-G)]. A non-THA AS control group was matched for age, sex, and disease duration. RESULTS: The mean age at AS disease onset for THA recipients was 19.5 yrs compared to 24.4 yrs for the total database (p < 0.05). The mean age at the first THA was 40.0 yrs. Of the 340 THA, 276 were primary (bilateral in 66%) and 64 were revisions. The mean followup for THA was 14.0 yrs (range 1-52). Overall, for the 340 THA, the patients considered outcome to be very good in 85%. In relation to the matched control group, THA patients were comparable for BASDAI, but had poorer function (p < 0.05) and lower global well being (p < 0.05). Of the 80 men under 60 years of age, 39 (49%) were employed compared to 49 (68%) of the control group (p < 0.01). Survival of original THA and revisions after 10, 15, and 20 yrs was 90%, 78%, 64%, respectively (originals), and 73%, 55%, 55%, respectively (revisions). CONCLUSION: The longterm outcome of THA in AS is outstanding. THA recipients have a younger age at onset than nonrecipients. The longterm survival characteristics of THA in young patients with AS is excellent.     

Assessments in ankylosing spondylitis

Assessment of disease status and response to therapy in ankylosing spondylitis is a rapidly expanding area of research. The assessment in ankylosing spondylitis international working group has contributed greatly to this development, defining core sets of health domains for use in daily practice and in clinical trials, developing and validating measurement instruments corresponding to these health domains, and developing response and remission criteria for use in clinical trials. This chapter reviews available measures of three major areas of disease impact in ankylosing spondylitis (disease activity, structural damage and functioning), and discusses which measures are relevant for use in clinical practice.