Patent Application: US-81166507-A

Abstract:
a novel use of the known protein erythropoietin , and / or a derivative , and / or a fragment thereof , is disclosed . epo is used as a pharmaceutical for the treatment of chronic inflammations . a particularly beneficial result is seen in patients suffering from rheumatoid arthritis . significant effects are seen in clinical variables such as morning stiffness , swollen joints , and the like .

Description:
this study focused on the effects of r - hu - epo on ra disease activity parameters . it is a part of a project studying the pathogenesis of acd and possible therapeutic strategies . the effect of r - hu - epo on the anemia and iron metabolism is reported in more detail . 21 ten patients with ra 22 were studied , fulfilling the criteria for acd as proposed by cartwright . 8 acd was confirmed by measuring stainable iron in a bone marrow preparation . patients treated previously with iron , vitamin b12 , folic acid and cytotoxic drugs were excluded . other causes of anemia were also excluded , such as the presence of hematuria , positive occult blood test in stool , decreased creatinine clearance , hemolysis and low vitamin b12 or folic acid . the demographic features of the studied patients are summarized in table i . all patients used a variety of non - steroidal anti - inflammatory drugs . recombinant human erythropoietin ( r - hu - epo , boehringer , mannheim , germany ), was administered three times a week at a dose of 240 units / kg subcutaneously at the right upper leg for six weeks . detailed clinical and laboratory evaluation was performed at entry and weekly by the same physician , until the end of the study ( six weeks ), then at nine and twelve weeks after onset of the study . routine laboratory procedures were used for assessment of hemoglobin ( hb ), hematocrit ( ht ), mean corpuscular volume ( mcv ), mean corpus hemoglobin ( mch ) and reticulocytes count . serum iron was measured spectrophotometrically ( instruchemie , hilversum , the netherlands ). transferrin and crp was assessed with a nephelometer ( ablon medical systems , leusden , the netherlands ) and serum ferritin by solid phase enzyme immune assay ( ferrizyme , abbott labs , chicago , usa ). the erythrocyte sedimentation rate ( esr ) was measured by the westergren method . the ritchie index , grip strength , number of swollen joints , morning stiffness and a subjective pain score ( visual analogue scale , 0 to 10 points ) were assessed as well . liver and kidney function tests were performed to monitor possible side effects . for evaluation , all clinical data were stored and analyzed on a wang personal computer using the lotus 1 - 2 - 3 program . statistical evaluation of the results was by fishers &# 39 ; exact test for group differences . p values of 0 . 05 or less were considered significant . in all ra patents , a rise in hemoglobin was observed ( table ii ). despite the wide range of values , the increase in hemoglobin became significant after the second week of treatment , compared to baseline values . when treatment was stopped , hemoglobin stayed significantly higher , compared to the baseline value , but dropped in the twelfth week . iron deficiency developed , as shown by the fact that five patients were characterized by ferritin levels lower than 40 mg / ml . a decrease in esr was found in all patients ( table iii ), which started at the third week of treatment and remained so until the end of the study . as illustrated , the decrease in eight patients was more than 20 % of their baseline value , which was highly significant . the same holds true for the crp values , but due to the wide range in the absolute values and small number of investigated patients , no significance could be calculated . however , expressing the values as a percentage of the baseline value , in this way after the third week of treatment , a significant decrease in the crp levels was also observed . both parameters ( ps and ms ) showed during the follow - up a tendency to decrease ( table iv ). caused by the variability in absolute values and small number of patients , a significance could not be calculated . when the values were expressed in a percentage of the baseline value , the ps decreased significantly after the third week of treatment and the ms after the sixth week . objective disease activity scores : grip strength ( gs ), ritchie index ( rd and number of swollen joints ( sj ) all parameters as shown in table v showed a continuous tendency towards improvement that lasted during , and also after , the treatment period . in the absolute changes in number of tender joints , a significant decrease could be calculated from the third week of treatment . also , a continuous decrease in the number of swollen joints was observed from t3 on and , at t9 , nine out of ten patients had less swollen joints , which was highly significant . caused by the variation of the individual values of the gs , it was impossible to calculate a significance . however , when the values were expressed as a percentage of their baseline values after three weeks of treatment , a significant increase in gs was noted . it should be mentioned that the gs remained stable in three patients during our investigation . all patients were treated for more than two months with the mentioned disease - modifying anti - rheumatic drugs . ** marks the treatment period when the differences compared to baseline values became significant . 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