PHARMACOLOGY OF BIOLOGIC MEDICATIONS

Unutar skupine upalnih bolesti crijeva dva su najpoznatija entiteta - Crohnova bolest i ulcerozni kolitis. Razumijevanje njihove patofiziologije te slijeda inflamatorne kaskade dovelo je do otkrića lijekova koji mogu selektivno djelovati na određenu molekulu ili signalni put te ispraviti neravnotežu proinflamatornih i antiinflamatornih medijatora. Prvi su razvijeni antagonisti TNF-; solubilni receptori poput etanercepta te monoklonalna antitijela. Infliksimab je širom svijeta odobren za liječenje umjerenog do teškog te fistulizirajućeg oblika aktivne Crohnove bolesti te teškog oblika ulceroznog kolitisa u odraslih bolesnika koji ne reagiraju na punu i adekvatnu terapiju nekim kortikosteroidom i/ili imunosupresivom, odnosno u onih koji ne podnose ili u kojih postoje medicinske kontraindikacije za takvu terapiju te za liječenje teškog oblika aktivne bolesti kod djece. Razvoj antitijela na infliksimab koji dovode do gubitka djelotvornosti lijeka i alergijskih reakcija otvorile su mjesto primjeni adalimumaba. Na osnovi dostupnih podataka iz pretkliničkih i ranih faza kliničkog ispitivanja još jedan TNF-antagonist (certolizumab), inhibitori Th 1 polarizacije (fontolizumab, ustekinumab) te inhibitor selektivnih adhezijskih molekula (natalizumab) potencijalno kandidiraju za nove biološke lijekove u liječenju upalnih bolesti crijevaTwo major types of inflammatory bowel diseases (IBD) are Crohn’s disease (CD) and ulcerative colitis (UC). Insights into their pathophysiology and inflammatory cascade have lead to the discovery of medications that can have a selective effect on a particular molecule or signal pathway and correct an imbalance in pro- and anti-inflammatory mediators. The first to be developed were the TNF-antagonists, soluble receptors like etanercept and monoclonal antibodies. Infliximab has been approved worldwide for treatment of moderate to severe and active fistulizing forms of Crohn’s disease, as well as for severe forms of ulcerative colitis in adults who do not react to full and adequate corticosteroid and/or immunosuppressive therapy, i.e. for patients who have problems with or medical contraindications to such therapy and for treatments of severe forms of active disease in children. Adalimumab can be applied in cases when antibodies develop as a reaction to infliximab, leading to reduced drug efficacy and allergic reactions. According to the available data from preclinical tests and earlier phases of clinical tests, potential candidates for new biological medications in treating IBDs are another TNF-antagonist (certolizumab), inhibitors of Th1 polarisation (fontolizumab,ustekinumab) and selective adhesion-molecule inhibitors (natalizumab