Effects of Tranilast on Pharmacokinetics of Methotrexate (MTX) in Patients With Rheumatoid Arthritis (RA)
Status:
Withdrawn
Trial end date:
2009-09-01
Target enrollment:
Participant gender:
Summary
The treatment of rheumatoid arthritis has improved considerably in recent years with the
understanding that better outcomes can be achieved by optimising the dosage schedule of
conventional drugs that suppress the inflammatory response in joints. Furthermore, the
development of protein based drugs that are given parenterally (i.e. by subcutaneous
injection or intravenous infusion), known as biologics, have given rise to even better
clinical results. However, despite this over 60% of patients with rheumatoid arthritis can
still be expected to have an unacceptably high degree of disease activity and the
prohibitively high cost of biologic therapy has resulted in rationing following NICE review.
Therefore there is a need for more effective and less costly treatment.
The proposed study is designed to test potential drug interactions between one such candidate
oral treatment, tranilast, and the gold standard therapy for rheumatoid arthritis,
methotrexate, which is given as a once weekly oral, intramuscular or intradermal regimen. The
drug to be tested, tranilast, an analogue of a naturally occurring molecule that regulates
inflammatory responses, is currently used in the treatment of allergic inflammation and has
recently been shown to be effective in an animal model of multiple sclerosis. Tranilast is an
analogue of a naturally tryptophan metabolite. Laboratory studies of cell biology indicate
that this molecule inhibits a number of key inflammatory pathways and the function of white
blood cells that play a critical role in the inflammatory features of rheumatoid arthritis.
The aim of this study is to assess whether tranilast may be useful for the treatment of RA.
In an animal model of rheumatoid arthritis, initial assessment showed that prophylactic
administration of tranilast interfered with the development of disease. Therapeutically, in
an animal model of arthritis, tranilast was very effective, and reduced all aspects of the
disease, including joint swelling, clinical score, and histological damage in a
dose-dependent fashion, and reduced pain. This degree of benefit compares well with
therapeutics that have been highly successful in humans, such as anti-TNF therapy.
Furthermore studies at the Kennedy Institute of Rheumatology Division, Imperial College
suggest that tranilast has a greater analgesic effect than the potent steroid dexamethasone
at effective anti-inflammatory doses