EFFECT OF LEFLUNOMIDE (A NEW DISEASE MODIFYING ANTI:RHEUMATIC DRUG), METHOTREXATE AND THEIR COMBINATION IN THE TREATMENT OF ADJUVANT ARTHRITIS
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This work was carried out in order to compare the effect of lefiunomide, methotrexate and their combination in the treatment of adjuvant induced arthritis in rats. 50 rats were divided into 5 equal groups, the 1st group was normal control rats, the 2nd group was arthritic non treated control rats, the 3rd, 4th and 5th groups, were arthritic rats received leflunomide (at a loading dose of 45mg/lcg orally for 3 drys, followed by 9mg/kg/dcty orally), methotrexate (0.75 mg /Kg 11W once weekly) and combination of lefiurtomide + methotrexate (in the same previously mentioned doses) respectively. One month after initiation of the treatment the results revealed that: lefiunomide, methotrexate and their combination signcantly (P<0.001) reduced the mean volt /Ps of the hind paws thickness of the arthritic rats and the percentage reduction of the hind paws swellings were 9096. 64.09 and 96.07% respectively . Furthermore, lefiunomide, methotrexate and their combination significantly (P<0.001) increased the mean values of the hind paws pressure shresholds of the arthritic rats and the percentage increase of the pressure thresholds were 89.52%, 69.8% and 97.75% respectively . These results were also confirmed by the histopathological examination of the ankle joints of the different groups, lefiunomide was superior to methotrexate in the repair of the destructive lesion, meanwhile the combination therapy showed marked improvement in the repair process than that observed by each drug alone . Treatment with leflunomide. methotrexate or their combination did not induce any significant changes in H896, total RBCs count, platelets count, serum urea and creatinine and total serum bilirubirt, meanwhile there were signcant decreases in the total WBCs counts and significant increases in liver enzymes (SCOT & SGPT). No differences were observed in all the tested haPmatological and biochemical parameters between the group treated by the combination of leflunomide and methotrexate and the groups treated by leflunomidy or methotrexate separately. The histopathological examination of the kidneys and livers supported the previous results. In conclusion, leflunomide is superior to methotrexte in the treatment of adjuvant arthritis and their combination offers additional efficacy while remains relatively safe.