Re: Hueber et al. Sensitivity and specificity of anti-Sa autoantibodies for rheumatoid arthritis

P. Jobanputra

Department of Rheumatology, Selly Oak Hospital, Birmingham B29 6JB, UK

Sir, I read with interest the report by Hueber et al. [1] on anti-Sa, a potential new serological test for diagnosing rheumatoid arthritis (RA). The authors report a highly specific, but rather insensitive, test for RA and concede that further studies are required to judge the precise utility of this test. It is important that patients with early disease (in their case disease duration less than 3 months) are evaluated when determining the utility of a diagnostic test, especially in a disease such as RA. However, there are difficulties when researchers feel obliged to rely substantially on the 1987 American Rheumatism Association (ARA) criteria for a diagnosis of RA, since in practice a substantial proportion of patients with a clinical diagnosis of RA may not fulfil these criteria [2, 3]. As a new diagnostic test must find utility in routine practice, these issues ought to be addressed. Not doing so could result in an inaccurate estimation of a test's utility. For example, Hueber et al. do not wholly rely on the ARA criteria as a ‘gold standard’ test since patients with systemic lupus erythematosus (SLE) and other rheumatic diseases who fulfil the 1987 ARA criteria for RA (29 of 180 patients) were not analysed in their 2 x 2 table as having RA. Doing so results in the following 2x2 table:

ARA criteria ARA criteria


yes

no



Anti-Sa +ve 24 1 25
Anti-Sa -ve 72 150 222
96 151 247

This yields data (sensitivity 0.15, specificity 0.99) very similar to their own data (sensitivity 0.19, specificity 0.98). Their data rely on classifying RA patients on the basis of ARA criteria and clinical judgement coupled with clinical observation (for example, in their group of early arthritis patients). This is entirely sensible, but what is key is that patients with a clinical diagnosis of RA not fulfilling ARA criteria were not tested.

Another consideration is the setting in which a diagnostic test is to be applied. A new diagnostic test for RA, if it is to be effective in the goal of delivering appropriate early treatment for patients, should find use in a primary care setting. This yields a likelihood ratio, using my calculations from their data, and using ARA criteria as a gold standard, of 25 for positive anti-Sa. This produces a post-test probability, assuming a pre-test probability of RA of around 1% in a primary care setting, and using appropriate nomograms [4], of approximately 20% results (if the test is positive). These figures are impressive but of concern is the poor sensitivity of anti-Sa. For example, 81% of their early arthritis patients were negative for anti-Sa. Even in combination with anti-A2/RA33 and rheumatoid factor, 13 of their 31 patients (42%) with early RA were negative for all three antibodies. On this basis it is difficult to see how anti-Sa can find use in routine practice.

References

  1. Hueber W, Hassfeld W, Smolen JS, Steiner G. Sensitivity and specificity of anti-Sa autoantibodies for rheumatoid arthritis. Rheumatology 1999;38:155–9.[Free Full Text]
  2. Harrison BJ, Symmons DP, Barrett EM, Silman AJ. The performance of the 1987 ARA criteria for rheumatoid arthritis in a population based cohort of patients with early inflammatory polyarthritis. J Rheumatol 1998;25:2324–30.[ISI][Medline]
  3. Dugowson CE, Nelson JL, Koepsell TD. Evaluation of the 1987 revised criteria for rheumatoid arthritis in a cohort of newly diagnosed female patients. Arthritis Rheum 1990;33:1042–6.[ISI][Medline]
  4. Fagan TJ. Nomogram for Bayes' theorem. N Engl J Med 1975;293:257.[ISI][Medline]
Accepted 8 September 1999





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