Naslov (srp)

Procena sigurnosti i efekta primene antiagregacione terapije kod bolesnika sa srednje teškom formom ulceroznog kolitisa

Autor

Petrović, Stanko S., 1973-, 55092233

Doprinosi

Tarabar, Dino, 1960-, 9946471
Zdravković, Nataša, 1973-, 11114087
Đukić, Svetlana, 1974-, 11623015
Sokić-Milutinović, Aleksandra, 13799527

Opis (eng)

Background/Aim: It has become clear that platelets play important role in pathogenesis of ulcerative colitis, due to their role in hemostasis and intestinal microthrombosis - which represents the earliest histopathological finding in mucosa of these patients and the fact that platelets are proinflammatory cells, that upon activation, release a multitude of molecules from their granules and thereby amplify inflammation. The aim of our clinical study was to evaluate safety ant efficacy of antiplatelet therapy - Brilique in patients suffering from moderate form of ulcerative colitis. Methods: Forty patients suffering form the moderate form of ulcerative colitis are included into this randomized, double blind, prospective study with parallel design, being previously treated with sistemic or local mesalazin, Sulfasalazin or Pentasa. Patients are randomized in two groups: standard group, which received standard therapy (Imuran tbl 2mg per kilogram of body weight, Prednison 40mg daily, with dose tapering to 20mg daily, and after three months of therapy with Prednison, tapering and exclusion from therapy) and Placebo, and second group, which received standard therapy plus Brilique tablet 90 mg once daily, for three months. Total colonoscopy with biopsies and assigned Nancy score were performed twice in all patients: before treatment and in the period of one to three months from the beginning of treatment. AST, ALT, magnesium, CRP, sCD40L, sP-selectin, IL-6, IL-13, TNF-α , IFN γ, IL-17A, IL-17F, IL21, IL-22, IL-4, IL-5, IL-2, IL-9, IL-10, ADP dependent platelet aggregation (from blood), and fecal calprotectin were performed in all patients at the beginning of treatment, on the seventh day and 30 days from the beginning of treatment. Statistical analysis of the data was completed using the PASW Statistics 18® statistical software package. Adverse drug reactions were monitored during this clinical study, especially increased intestinal or occurrence of extraintestinal bleeding, thrombocytopenia, bradycardia, dyspnea. Results: We found significantly lower average values IL-2 and value differences in IL-6, TNFα, IL-17A, IL-21, IL-22, IL-9 in patients who received Brilique which is associated with decrease in sCD40l and sP-selectin, comparing to the standard group of patients, on the seventh day from the beginning of the treatment. Six patients reported minor bruises on the skin of the legs, lasting for 7-10 days. No other side effect of the drug was reported. Conclusion: results obtained from this clinical study support the potential of antiplatelet therapy for treating patients suffering from ulcerative colitis, together with standard therapy.

Opis (srp)

Uvod/Cilj: Trombociti imaju važnu ulogu u nastanku ulceroznog kolitisa obzirom na njihovu ulogu u hemostazi i stvaranju mikrotrombova u malim krvnim sudovima sluznice kolona što predstavlja prvu patološku promenu u ulceroznom kolitisu, i činjenicu da su oni proinflamatorne ćelije, da nakon aktivacije oslobađaju veliki broj biološki aktivnih supstanci i time potenciraju inflamaciju. Osnovni cilj našeg istraživanja je bio da se ispita bezbednost i efikasnost primene leka Brilique, koji smanjuje agregaciju i aktivnost trombocita, kod bolesnika sa srednje teškom formom ulceroznog kolitisa u pogoršanju. Metode: U ovu dvostruko slepu, randomizovanu prospektivnu kliničku studiju sa paralelnim dizajnom, uključili smo 40 bolesnika sa srednje teškom formom ulceroznog kolitisa u pogoršanju, koji su prethodno lečeni sistemskom i lokalnom primenom preparata Mesalazina, Sulfasalazinom ili Pentazom. Bolesnici su randomizovani u 2 grupe: standardnu grupu koja je lečena standardnom terapijom (Imuran 2 mg na kilogram telesne mase uz Prednison, u početnoj dozi od 40 mg dnevno, sa postepenim smanjenjem doze do 20 mg dnevno, a nakon 3 meseca uzimanja Prednison-a, isti bi postepeno isključio iz terapije) uz Placebo, i grupu koja je lečena standardnom terapijom uz Brilique tablete 90 mg jednom dnevno, tokom 3 meseca. Kod svih bolesnika je pre početka ispitivanja i u peridou od mesec dana pa do isteka 90 dana od početka ispitivanja urađena kolonoskopija i određen Nancy score. Na početku studije, 7. i 30. dana od početka ispitivanja kod svih bolesnika određivani su, u krvi, kompletna krvna slika, urea, kreatinin, glukoza, albumin, kalijum, holesterol, trigliceridi, AST, ALT, magnezijum, CRP, sCD40L, sP-selectin, IL-6, IL-13, TNF-α , IFN γ, IL-17A, IL-17F, IL-21, IL22, IL-4, IL-5, IL-2, IL-9, IL-10, ADP zavisna agregacija trombocita i fekalni kalprotektin u stolici. Potom su analizirane dobijene vrednosti parametara koje smo pratili, a sve vreme su praćeni neželjeni efekti terapije (pojačano intestinalno ili novonastalo ekstraintestinalno krvarenje, trombocitopenija, bradikardija, dispneja). Rezultati: u grupi bolesnika koji su primali Brilique, u odnosu na standardnu grupu, došlo je do ispoljavanja antiinflamatornog dejstva leka Brilique, što se manifestovalo značajno nižim prosečnim vrednostima IL-2 i razlikama vrednosti IL-6, TNF-α, IL-17A, IL-21, IL-22, IL-9, 7. dana od početka isptivanja, a što je praćeno sniženjem sCD40L i sP-selectin u krvi. Osim modrica po koži donjih ekstremiteta kod 6 bolesnika, koje su se povukle nakon 7-10 dana, nije zabeležen nikakav drugi neželjeni efekat terapije sa Brilique-om. Zaključak: nakon primene leka Brilique kod bolesnika sa srednje teškom formom ulceroznog kolitisa u pogoršanju došlo je do ispoljavanja antiinflamatornog efekta, što može imati veliki klinički značaj.

Jezik

srpski

Datum

2020

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 2.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 2.0 Austria License.

CC BY-NC-ND 2.0 AT

http://creativecommons.org/licenses/by-nc-nd/2.0/at/