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SP0054 The concept of treat-to-target
  1. J Braun
  1. Rheumazentrum Ruhrgebiet, 44649 Herne, Germany


Many illnesses including most rheumatic diseases have substantial effects on well-being and quality of life, including deterioration of physical and mental function and a reduced life expectancy, since they can cause damage to organs and cells. If healing and regeneration cannot be achieved an impairment of organ function can be expected. In acute diseases this may occur rapidly over hours to days and weeks, while it often takes months to years in chronic diseases. However, if treatment is instituted early enough, organ damage may be prevented or diminished.

Critical for an optimal management of diseases with potentially severe outcomes is to determine the responsible thresholds for, for example, disease activity or to define the maximum level of a surrogate marker at which damage is unlikely to occur and, thus, will not be harmful in the long term. Although the optimal aim of therapy is cure, and appropriate therapy may even normalize life expectancy, many chronic diseases such as hypertension, diabetes, rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have remained without curative therapies in the last decades – even though considerable progress has been made. Thus, a strategic therapeutic approach should aim for prevention of future damage, and maximal improvement of compromised organ function. Therefore, a clearly defined threshold of a validated measure that predicts future harm or no or minimal harm, is a target of critical importance for chronic diseases with potentially severe outcomes. Treat-to-target strategies having been developed to achieve this have widespread implications. They should be routinely followed - as long as the potential harm from treatment is carefully balanced against its benefit. Clearly, if inappropriately managed, the consequences of diabetes and hypertension in the long run include, myocardial infarction, stroke, renal failure, blindness, etc. Therefore, target values for biological markers have been determined below which organ damage does usually not occur and life expectancy is normalised. Examples for domains in which such thresholds have been defined are blood pressure, glycosylated haemoglobin (HbA1c), and others.

Inflammatory rheumatic diseases lead to organ damage not only in the musculoskeletal system but they may also harm internal organs. A target level of a measure related to its long-term outcome, can be a surrogate measure like the cholesterol level for cardiovascular diseases, or a composite measure of disease activity as used in RA (DAS28) or in AS (ASDAS). The treat-to-target strategy can be reduced to a simple algorithm of, on the one hand measuring activity and on the other hand, in consequence, adapting treatment. Treatment adaptation does not necessarily mean changing a medication or increasing the dosage of a drug but may even also mean life style changes, as long as the therapeutic target is attained or nearly attained - importantly within a prespecified time frame. Therapeutic adaptations should always take patient factors, including comorbidities, adverse events and patient preferences, into account.

However, the musculoskeletal system can mostly not be assessed by using a simple surrogate or direct “gold standard” measures, since rheumatic diseasese with multiple signs and symptoms are mostly rather complex. In RA information derived from physical examination using a quantitative joint count is considered very important. This is different in AS. Additionally, information from the history, which can be collected through patient self-report multifaceted questionnaires, has proven effective in determining patient status and its change. This is even more important in AS. However, functional impairment has reversible and irreversible components. Damage is a consequence of high and/or persisting disease activity. The most important variables contributing to joint damage in RA are swollen joint counts and C-reactive protein (CRP). The latter in combination with questions on back pain is also important in AS, while in RA the use of composite measures of disease activity that comprise joint counts is critical. There is good evidence that, if this strategy is consequently followed, physical function will improve and joint damage be reduced in patients with RA. To determine optimal treatment targets in RA it is necessary to define the thresholds of disease activity measures at which progression of joint destruction is halted. Of note, only remission is associated with maximal reversal of functional impairment and a stop of progression of damage as well as work disability. However, it needs to be realized that some remission criteria are more stringent than others.

Disclosure of Interest None declared

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