Current Therapeutic Approaches in Inflammatory Bowel Disease

Amir      Ali Sohrabpour; Reza      Malekzadeh; Ali      Keshavarzian

doi:10.2174/138161210794079155

Abstract

Inflammatory bowel disease (IBD) is a chronic, relapsing, inflammatory disorder of the gastrointestinal tract and is broadly classified into Crohns disease (CD) and ulcerative colitis (UC). In the last decade, our understanding of the etiology and pathogenesis of this group of disorders has been improved. More specifically, recent development of biologics and use of immunomodulator agents in IBD have made it possible to robustly control mucosal inflammation and heal mucosal ulcerations and thus provide an opportunity to potentially modify disease course and prevent complications and future surgery. However, unfortunately we have not identified reliable, sensitive and specific markers to predict disease course and to identify those patients with aggressive and progressive course that would benefit from early use of biologics to prevent future complication and surgery. Thus, optimal medical management of IBD has remained multifaceted and individualized. Our primary therapeutic goals have remained unchanged and are to: [1] improve patient quality of life by treating flare ups [induction of remission], maintaining remission, and treating symptoms like diarrhea; [2] predict and prevent/treat complication; [3] prevent/treat nutritional deficiency and maintain optimal nutrition, [4] provide appropriate psychosocial support, and of course [5] attempt to modify disease course in those with aggressive disease. We can achieve these goals by appropriate use of therapeutic agents that include 5-aminosalicylates, corticosteroids, immunosuppressive agents, antibiotics, nutritional support, and the biologic agents. Information from well designed double blind placebo controlled trials combined with knowledge of the potential impact of patient and disease characteristics on disease course which can assist us to individualized treatment plan will be the guide for us to appropriately use these therapeutic agents. For example, age of the onset of the disease, patient gender and race, mode of the disease presentation, disease location, disease-associated complications such as perianal disease/fistula, and serology and genetic markers can all help to individualize disease treatment. These factors can help to determine whether one should start with 5-ASA/antibiotic/steroid [step-up where there is no risk factors for aggressive disease course] or whether one should initiate biologic therapy at diagnosis [top-down approach], and whether it is most advisable to use monotherapy with biologic treatment [e.g. in young, Caucasian male or elderly] or use a combination therapy with a biologic and an immunomodulator. Ongoing research promises, in a near future, development of more robust set of markers to be able to model disease behavior to more accurately predict disease course and thus decide on therapeutic approach with most appropriate efficacy/risk ratio for a given patient. Furthermore, current basic laboratory research has provided a large number of potential therapeutic targets to treat IBD with new promising highly specific and targeted agents.

Keywords: Inflammatory bowel disease, Crohn's disease, Ulcerative colitis, treatment, anti-TNF antibodies, gastrointestinal tract, mucosal inflammation, 5-aminosalicylates, corticosteroids, immunosuppressive agents, antibiotics, Caucasian, Perianal disease, abscesses, Sulfasalazine, cyclooxygenase, lipoxygenase, B-cells, peroxisome proliferators activated receptor ligand, NFkB, balsalazide, olsalazine, CD Activity Index, Asacol, mesalamine, colonic disease, mesalazine, chromosomal DNA, glucocorticoid, azathioprine, mercaptopurine, methotrexate, leukopenia, nonalcoholic steatohepatitis, mycophenolate mofetil, ciprofloxacin, rifaximin, metronidazole, tobramycin, antibiotic resistance, certolizumab, Natalizumab