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SP0031 Biomarkers: the Future or Waste of Resources: the Evidence behind Laboratory Biomarkers
  1. H.-M. Lorenz
  1. Medicine V, Rheumatology, University Hospital, Heidelberg, Germany

Abstract

Biomarkers might be helpful for (early) diagnosis and risk stratification in certain diseases, biomarkers might predict response to a certain drug/biologic agent and side effects of medications. Lastly, biomarkers might help to judge the risk of mortality and define compliance of the patients to therapy. In practical terms, however, in rheumatology only a few biomarkers are really helpful to date for the above mentioned intentions. Disease specific antibodies like rheumatoid factor, CCP antibodies, antibodies against proteinase 3, myeloperoxydase, dsDNA or nucleosomes help to define the disease entity, clinical symptoms, however, are still the leading indicators of the disease. Genetic markers are more or less specific: specific in the definition for example of recurrent fever syndromes or other genetically driven diseases. HLA-B27 is helpful, but can never define a disease alone. Protein serum levels, for example the concentration of ferritin (in autoinflammatory diseases) or CRP as indicator of inflammation are of use in the judgement of disease activity, but neither specific nor sensitive for the diagnosis. Biomarkers for risk stratification of certain diseases or flare of the diseases have been better established: rheumatoid factor and CCP antibodies, CRP, the number of erosions or swollen joints in arthritis, the age influencing the risk of infections, phospholipid antibodies for events like thromboses or pregnancy complications, the gender again in rheumatoid arthritis. There are some useful serological biomarkers which are helpful in the judgement of disease activity like complements in lupus or CRP in rheumatoid arthritis and others. In contrast, some yielded disappointing results like PR3 antibody titers in GPA. The amount of proteinuria is a good indicator for the risk of chronic kidney failure. Prediction of response to a certain drug or a biologic antibody is urgently needed. Many laboratories proposed certain markers which mostly could not be confirmed by other labs or in a population with different genetic backgrounds. Most promising might be multi-parameter assays combining protein levels as well as genetic markers in a matrix. This might perhaps double the probability of good responses to biologics. These assays are not established in routine praxis, however. There are many papers which propose genetic markers or polymorphisms increasing response for example to TNFa-antibody therapy, these genetic polymorphisms might be relevant in certain populations but might not account in another population with a different genetic background. Well established predictors of side effects are asian ancestry (Methotrexat tolerance) or genetic polymorphisms in the Thiopurin-Methyltransferase (TPMT) gene (Azathioprine tolerance). Risk factors for a lethal acute coronary event have been well established. NT-pro-BNP is a well confirmed risk factor for death in pulmonary arterial hypertension. Compliance of the patients can be sometimes defined by measurement of serum drug level (Cyclosporin A) or bone turn over markers in therapy of osteoporosis. In conclusion we all use biomarkers for any of the above mentioned intentions. However, we all know that clinical experience, knowledge and good guidance of the patients and their disease are still much better predictors of response and risk prevention than any biomarker to date. This might change in the upcoming years as many research efforts are being spent in biomarker development.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.6101

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