New clinical treatments

  • Chevalier X
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Abstract

Purpose: Currently available pharmacological treatments for OA can relieve pain temporarily, but since we don't have any therapy which may substantially slow down the progression of the disease. Thus there is a real need for disease modifying OA drug as well as need for drug which act as long term pain killer. At best the "ideal" drug should both decrease pain, improve function and acts on structure. Treatments with cellular transplants are not under the scope of this review. New therapeutic options in OA have largely benefit from a better understanding of the pathophysiology of OA. Osteoarthritis is now regarded as an organ failure which associated at variable degrees, inflammation of the synovial membrane, increase in the subchondral bone turn-over and destruction of the cartilage extracellular matrix. Aim of new therapies is focused on one of this tissue process. This review will give an update of the available new trials in OA as well as future possible directions. Methods: This review has been focused on clinical studies in humans performed with so called MeSH terms: osteoarthritis, anti NGF, biologics, growths factors, subchondral bone, anti osteoporotic drugs, stems cells, gene therapy, lubricin, PRP. PubMed Medline search was conducted through January 2013.We also looked to abstracts frommain OA congress and to ongoing registered clinical trials in OA. Results: Several randomised controlled studies have now merged using biologics in OA. Biologics hold considerable promise for OA therapy since their effect in others rheumatic inflammatory diseases like rheumatoid arthritis were dramatic. One should differentiate the drugs only targeting pain such as anti nerve growth factor antibodies from the one with a more structure disease modifying profile such as anti cytokine therapy. Anti NGF therapy raises promising results, though recording of cases of rapid destructive arthropathy deserves some caution. Biologics using anti interleukin-1 agents in knee OA raises negative results on the evolution of pain and none study has been built to regard the chondroprotective action of those IL-1 blockers. Tumor necrosis alpha blockers have been tried mainly in hand OA with disappointing results both on the structural evolution and on pain. Similarly anti nitric oxide agents failed in a long term study to slow down the progression of knee OA. Owing to these repeated negative results with biologics, new strategies should be contemplated such as gene therapy. On the other hand, new emerging treatments may be more related on the repair side of cartilage. This could be targeted by using growth factor delivery. Intra articular administration of autologous platelets is widely used by the level of proofs still need to be confirmed in large randomized trials. One placebo controlled study using repeated intra articular administration of FGF 18 failed to demonstrate neither any pain relief nor any structural changes. The therapeutically option consisting in the intra articular administration of autologous stem cells is ongoing in a phase 1 study in humans. In the next future, new lubricants agents such recombinant lubricin also offers an appealing approach. Finally, recent placebo controlled study with ranelate strontium, a decoupling bone agent, showed promising results on the evolution of joint space narrowing in patients with knee OA. Conclusions: Looking for new treatments options in OA should not only consider new drugs with an appealing mechanism of action but should also consider to whom patient and when those therapies could be at best prescribed.

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APA

Chevalier, X. (2013). New clinical treatments. Osteoarthritis and Cartilage, 21, S3–S4. https://doi.org/10.1016/j.joca.2013.02.018

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