Patient characteristics
There were 74 newly diagnosed cases who met the study criteria. The annual number of diagnoses was broadly similar between 2000 and 2006 (representing an incidence of approximately 4/100,000 registered patients per year) but fell after 2006 – this coincided with a progressive reduction in the size of the database as GP practice computer systems were replaced.
Cases were matched to 296 population controls and 169 symptomatic controls. 53 cases (72%) were men and median age at diagnosis of AS was 37 years (interquartile range 31 to 43).
Data quality
54 cases (73%) were registered with the same GP practice (and therefore had continuous records in the PTI database) for at least six years before diagnosis. Similar proportions were seen for population and symptomatic controls (81% and 72 % respectively). A code for one or more prescription of an appropriate treatment (e.g. a NSAID) was present for 68 cases (92%). Diagnostic tests were coded less often – any relevant diagnostic code (such as for a full blood count, ESR or x-ray) was present in only 30 cases (41%).
Occurrence of diagnostic features
The numbers and proportions of patients with at least one instance of each feature, either in the 3 years prior to the index date or at any time are shown in table 2 (vs. population controls) and table 3 (vs. symptomatic controls). Tables 2 & 3 also show the ORs (with 95% CIs) for the two comparisons.
As expected axial pain was more common in cases than population controls (OR 9.8, 95% CI 5.1 to 18.9) but not than symptomatic controls (OR 1.0, 95% CI 0.6 to 1.8) in the three years period before the index date. Tendon related disorders and iritis were both more common in cases than population controls (OR 3.4, 95% CI 1.3 to 8.7 and OR 32.0, 95% CI 4.0 to 255.9) but were recorded in only 21% and 16% of cases respectively. Urethral symptoms were infrequently recorded in all groups. Fatigue was not more common in cases when compared to population and symptomatic controls (OR 1.9, 95% CI 0.8 to 4.2 and 2.1, 95% CI 0.8 to 5.7) respectively. A history of inflammatory bowel disease was present in 16% of cases at any time before diagnosis. Codes indicating recording of x-rays and MRI scans were rare among cases and controls.
Occurrence of prescribed treatments
In both the population and the symptomatic group comparisons, both analgesics (OR 6.0, 95% CI 3.3 to 10.8 and OR 2.0, 95% CI 1.1 to 3.6) and NSAIDS (OR 12.9, 95% CI 6.3 to 26.8 and OR 3.6, 95% CI 1.8 to 7.1) were more commonly prescribed in the three year period before the index date to cases than controls. Prescriptions of tricyclic antidepressants, typically prescribed for chronic pain, were more common compared to population controls, unlike prescriptions for other antidepressants.
Composite features
Table 4 shows the number and proportion of patients with at least one instance of each of the composite features over the three years before date of diagnosis/ matching. Several composite features appeared relatively infrequently. Only three occurred in more than 15% of cases: distinct episodes of axial pain separated by more than 6 months (OR 12.7, 95% CI 4.5 to 34.6); the occurrence of axial pain with and tendon symptoms within the same year (OR 21.7, 95% CI 2.6 to 181.5); and the co-occurrence (within 30 days) of axial pain and a prescription for nonsteroidal anti-inflammatory drug (OR 10.4, 95% CI 4.9 to 22.1).
Occurrence of diagnostic features over the time prior to diagnosis.
Figure 1 shows histograms of the number of years between first episode of back pain or NSAID prescription and diagnosis (or matching) for cases and symptomatic controls. The median time between first coded episode of back pain and diagnosis of AS was 4 years (interquartile range 2 to 7). For the same patients the median time between first prescription for a NSAID was 4 years (interquartile range 2 to 6). Figure 2 shows plots of eight diagnostic features, showing the ORs for three-year time windows with different intervals between the end of the three-year window and the diagnosis / matching date. Each plot compares cases with matched population controls (in blue) and matched symptomatic controls (in red). In all plots, 95% confidence intervals are indicated by dotted lines. The comparison with population controls demonstrates the development of features over time. The comparison with symptomatic controls indicates whether features have different predictive value in diagnosing symptomatic patients at different stages.
The plot for axial pain shows that the odds ratio for coded episodes of axial pain rose steadily from the three year period ending 3years before diagnosis to the three year period ending at the time of diagnosis when compared to population controls. On the other hand, the plots for large joint symptoms and (in the two years prior to diagnosis) enthesopathy suggests little or no time trend. The combination of axial pain and large joint symptoms – while relatively infrequent – shows a strong signal beginning at least 2 years before diagnosis.