Review article: new drug formulations, chemical entities and therapeutic approaches for the management of ulcerative colitis

Abstract

Summary Background Treatment options for ulcerative colitis (UC) are expanding with the development of novel drug formulations and dosing regimens and new chemical entities. Although the goals of medical therapy for UC remain unchanged, that is to induce and to maintain remission, focus has also centred on improving patient compliance, modifying the natural course of disease and healing the mucosa. Aim To examine novel formulations, new chemical entities and novel therapeutic approaches to the management of UC. Methods Searches for all studies related to UC treatment in Medline and abstracts from major national and international meetings published in the last 10 years. Results 5‐Aminosalicylic acids (5‐ASA) remain the standard first‐line treatment for patients with mild to moderately active UC. New formulations with altered delivery, and new dosing regimens have demonstrated possible improvements in efficacy compared with historically available preparations and dosing patterns. Once‐daily dosing, micropellet formulations, and high‐dose tablets offer enhanced efficacy and improved compliance. 5‐ASA is now recognized as a ligand for peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) and it has a role as a chemo‐preventive agent in long‐standing UC. New colonic release corticosteroid formulations help to limit systemic toxicity; turmeric, tacrolimus and infliximab have shown promising results. New anti‐inflammatory targeted therapies include an anti‐CD3 antibody, selective integrin blockers, anti‐IL‐2 antibody and PPAR‐γ agonists. Conclusion The evolution of novel oral 5‐ASA formulations and dosage regimens, and recent development of new molecules have expanded the therapeutic armamentarium of UC.

Efficacy of Rectal Tacrolimus for Induction Therapy in Patients With Resistant Ulcerative Proctitis

“…Tacrolimus and cyclosporin are classical calcineurin inhibitors and are widely used as immunosuppressive medications and have demonstrated promising results in the management of UC 7,8 . Calcineurin, or protein phosphatase 2B (PP2B), is a ubiquitously expressed cytosolic Ser/Thr protein phosphatase, that is highly conserved in eukaryotes 9 .…”

Consensus guidelines for the management of inflammatory bowel disease

“…Among the several action mechanisms of the 5-ASA action are modulation of proinflammatory cytokines secretion, inhibition of leukotriene and prostaglandin production, ability to scavenge free radicals and decrease oxidative stress, reduction of nuclear factor k-B (NF-kB), cell proliferation inhibition and apoptosis promotion. More recently, it has been shown that a great part of 5-ASA (mesalazine) action is due to its ability to activate PPAR-g (peroxisoma proliferator-activated receptor-g), which plays a role in inflammation control, cell proliferation and apoptosis (63) . Side effects of SSZ are more commonly dose-dependent and related to sulphapiridine serum levels.…”

Novel topical therapies for distal colitis

“…Tacrolimus and cyclosporine are classical calcineurin inhibitors that are widely used as immunosuppressive medications with some promising results observed in UC [7,8] . Calcineurin, or protein phosphatase 2B (PP2B), is a ubiquitously expressed cytosolic Ser/Thr protein phosphatase that is highly conserved in eukaryotes [9] .…”