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AB0147 Drug treatment of osteoarthritis: aspects of symptom and structure modification
  1. KK Förster,
  2. KW Schmid
  1. Department of Clinical Research, Opfermann Arzneimittel GmbH, Wiehl, Germany

Abstract

Background “Osteoarthritis (OA) is a degenerative disease of the joint cartilage. It is of diverse aetiology and obscure pathogenesis. Clinically, OA is characterised by joint pain, tenderness, movement limitation, occasional effusion, and variable degrees of local inflammation, but without systemic effects. Therapeutically, OA is characterised by a lack of specific healing”.1 Therefore, treatment of OA is mainly a symptomatic one, a specific treatment, with a demonstrable causal effect on the pathological process, is still on the way to be proven clinically.

Objectives Historically, OA has been viewed as a disease for which little can be done to block its progression. However, the significant increase in understanding the underlying pathologic processes has substantially increased the number of potential targets for drug intervention (Howell et al. 1995). In order to clearly define OA therapies, recently it was agreed to classify OA drugs as follows:

  1. Symptom modifying drugs (with no detectable effect on the structural changes of the disease).

  2. Structure modifying drugs (which interfere with the progression of OA).

Methods Based on published placebo as well as reference controlled clinical studies, evidence is assessed for the classification of drugs used in the treatment of osteoarthritis.

Results Besides corticosteroids, classical NSAIDs, and analgesics, symptom modifying OA pharmacotherapy includes Ademethionine, ASU, Chondroitin sulfate (CS), Diacerein, Glucosamine sulfate (GS, dona 2oo-S), Hyaluronic acid (HA), and Oxaceprol. All show an anti-inflammatory effect, but unlike classical NSAIDs most of them do not inhibit lip- or cyclo-oxygenase. Therefore, they have been described as nonclassical NSAIDs.2

On the other hand, experience based on in vitro studies and animal models shows that some drugs used in the treatment of OA, rather than having a beneficial symptomatic effect, may accelerate or exacerbate the pathological changes of OA (Brandt et al. 1998). This potential drug induced cartilage change for the worse has stimulated interest in pharmacologic agents which may positively influence the pathogenetic mechanisms in OA. In case these agents would be disease modifying (Lequesne et al. 1994) or structure modifying drugs (Dougados et al. 1996). Many substances have already been tested experimentally. However, a specific OA treatment has very rarely been confirmed so far in hypothesis testing clinical studies.

Concerning potential structure modification of CS and HA, there are only a few pilot clinical studies. Concerning GS, it was proven recently that during long-term treatment the drug exerts combined structure-modifying and symptom-modifying effects so that it is to suggest that GS could be a disease modifying agent in osteoarthritis (Reginster et al. 2001).

Conclusion A future challenge will be the design and implementation of further appropriate clinical trials (Dieppe 1994), with longer follow-up and with different designs, to assess whether disease modification leads to reduced need of joint surgery and prolonged time to substantial disability, respectively (Reginster et al. 1996).

References

  1. Mankin HJ, Brandt KD, Shulman LE. Workshop on etiopathogenesis of osteoarthritis. Proceedings and recommendations. J Rheumatol. 1986;13:1127–60

  2. Förster KK. Drug treatment of osteoarthritis: clinical aspects. In: Grifka J, Ogilvie-Harris DJ, eds. Osteoarthritis. Berlin Heidelberg New York: Springer-Verlag, 2000: 66–81

  3. Reginster JY, Deroisy R, Paul I, Lee RL, Henrotin Y, Giacovelli G, Dacre J, Rovati LC, Gosset C. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 1999;i:251–6

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