Medical Therapy For Ulcerative Colitis Research Articles

Pericardial Tamponade in a Patient with Inactive Ulcerative Colitis

Cardiac tamponade is a rare extraintestinal manifestation of ulcerative colitis. We present a case report of tamponade occurring four years after curative proctocolectomy and in the absence of any medical therapy for ulcerative colitis. Options for medical management of this condition are also discussed.

Treatment of inflammatory bowel disease: A review of medical therapy

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract. While a cure remains elusive, both can be treated with medications that induce and maintain remission. With the recent advent of therapies that inhibit tumor necrosis factor (TNF) alpha the overlap in medical therapies for UC and CD has become greater. Although 5-ASA agents have been a mainstay in the treatment of both CD and UC, the data for their efficacy in patients with CD, particularly as maintenance therapy, are equivocal. Antibiotics may have a limited role in the treatment of colonic CD. Steroids continue to be the first choice to treat active disease not responsive to other more conservative therapy; non-systemic steroids such as oral and rectal budesonide for ileal and right-sided CD and distal UC respectively are also effective in mild-moderate disease. 6-mercaptopurine (6-MP) and its prodrug azathioprine are steroid-sparing immunomodulators effective in the maintenance of remission of both CD and UC, while methotrexate may be used in both induction and maintenance of CD. Infliximab and adalimumab are anti-TNF agents approved in the US and Europe for the treatment of Crohn's disease, and infliximab is also approved for the treatment of UC.

Medical therapy of inflammatory bowel diseases: Ulcerative colitis

There are fewer significant changes in the medical therapy of ulcerative colitis (UC) compared to Crohn's disease. The most important factors that determine therapy are disease extent and severity. 5-aminosalicylates (5-ASA) constitute the treatment of choice in mild-to-moderate UC. The efficacy of new compounds (e.g. mesalazine) is only mildly improved compared to sulphasalazine; however, their use has become more frequent due to a more favorable side effects profile. Topical medication is more effective in proctitis and distal colitis, and the combination of topical and orally-administered drugs is superior to oral therapy alone also in extensive disease. Thus, this latter regimen should be considered for cases where the escalation of treatment is required. Systemic steroids still represent the first line therapy in acute, severe UC, while in patients who do not respond to steroids, cyclosporine and infliximab should be considered as a second line therapy and as alternatives for colectomy. Maintenance treatment is indicated in all UC cases. 5-ASA compounds are suggested as first line maintenance therapy with the optimal dose still being under investigation. Topical compounds are effective also for maintenance in distal colitis or proctitis, if accepted by the patients. Immunosuppressives, especially azathioprine, should be considered in chronically active, steroid dependent or resistant patients. According to recent publications, azathioprine is almost equally effective in UC and CD. The question of chemoprevention is important during maintenance. There are increasing data supporting the notion that aminosalicylates may lower the risk for UC-associated colorectal cancer. The most important changes in the management of UC are the more frequent use of topical aminosalicylates and azathioprine, the availability of infliximab in severe UC, and increasing use of aminosalicylates for chemoprevention of colorectal carcinoma. Furthermore, adequate attention is needed to better organize the patient-doctor relationship and for greater adherence to medical therapy.

Review article: colon‐saving medical therapy vs. colectomy in ulcerative colitis – the case for colectomy

In the era of expanding medical therapy for ulcerative colitis, surgery is still a very valid option in those patients, where medicine is not able to control symptoms, both in the acute and chronic stages, and also for those at risk of developing a cancer. The ileal pouch-anal anastomosis (IPAA) will, for the vast majority of patients, give a very acceptable functional outcome. There is a risk of surgical complications and pouchitis; however, mortality is very low and compares well with medical therapy. Reduced female fertility is a concern but compared with the preoperative state, overall sexual function is largely improved. The ileorectal anastomosis is undergoing a revival and can be used especially in the case of female fertility concerns. Either the continent ileostomy or a conventional ileostomy is an option for those 10-15% of patients who will eventually experience pouch failure, usually either because of septic complications or an unacceptable bowel function. Quality of life following both these options, and IPAA, is excellent and does not differ from that of the matched background population.

Positions of selective leukocytapheresis in the medical therapy of ulcerative colitis

Ulcerative colitis (UC) and Crohn's disease (CD) are the major forms of idiopathic inflammatory bowel disease (IBD). Both UC and CD are debilitating chronic disorders that afflict millions of individuals throughout the world with symptoms which impair function and quality of life. The etiology of IBD is inadequately understood and therefore, drug therapy has been empirical instead of being based on sound understanding of IBD pathogenesis. This is a major factor for poor drug efficacy and drug related side effects that often add to the disease complexity. The development of biologicals notably infliximab to intercept tumor necrosis factor (TNF)-alpha reflects some progress, albeit major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD seems to be perpetuated by inflammatory cytokines like TNF-alpha, interleukin (IL)-1beta, IL-6 and IL-8 for which activated peripheral granulocytes and monocytes/macrophages (GM) are major sources. Further, in IBD, peripheral GMs are elevated with activation behavior, increased survival time and are found in vast numbers within the inflamed intestinal mucosa; they are suspected to be major factors in the immunopathogenesis of IBD. Hence, peripheral blood GMs should be appropriate targets of therapy. The Adacolumn is a medical device developed for selective depletion of GM by receptor-mediated adsorption (GMA). Clinical data show GMA, in patients with steroid dependent or steroid refractory UC, is associated with up to 85% efficacy and tapering or discontinuation of steroids, while in steroid naive patients (the best responders), GMA spares patients from exposure to steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse suppresses relapse thus sparing the patients from the morbidity associated with IBD relapse. Further, GMA appears to reduce the number of patients being submitted to colectomy or exposure to unsafe immunosupressants. First UC episode, steroid naivety and short disease duration appear good predictors of response to GMA and based on the available data, GMA seems to have an excellent safety profile.

Update in Medical Therapy of Ulcerative Colitis

Recent advances in the pathogenesis of ulcerative colitis recognize the interface of genetic susceptibility, environmental factors (eg, gut microflora), and an altered host's immune response. The meteoric evolution of new therapies designed to address these pathogenetic factors may lead to confusing and often confounding treatment programs. This review is designed to assist the practitioner when in [corrected] incorporating new or novel therapies into a treatment program. These decisions are based on new clinical trial data and the experience of seasoned gastroenterologists with established remedies. NEWER CONCEPTS AND THERAPIES IN UC 5-ADA-- 1. Remains drug of choice for induction and maintenance of remission in mild to moderate IC.1,2 2. Rare but increased incidence of renal disease exists but benefits outweigh risks.18-20 3. Chemoprevention of colorectal cancer in UC is promising and may be related to higher dose and a lessened degree of inflammation.29-36 4. Bioequivalence of all USA 5-ASA is established. Choice of a 5-ASA preparation is not dependent on superiority of a particular mesalamine.3 Phosphodiesterase Inhibitor (OPC-6525)37: preliminary data promising Immunomodulators 6MP/AZA 1. long-term effect not waning51 2. concerns over lymphoma voiced but overall benefits outweigh risks64-70 3. 6MP metabolites measurements of increasing use52-56 Cyclosporine experience continues but serious adverse events remains.105-114 Biologics Infliximab--somewhat disappointing in CUC, awaiting RCT87-92 Basiliximab--useful as "steroid sensitizer" in previously steroid resistant patients118-120 Visilizumab--promising as alternative to cyclosporin in server U.C.115-117 Apheresis--and emerging "non-drug" treatment alternative121-135 Probiotics--Useful in pouchitis and some mild to moderate U.C.94-98, 154 ISIS topical therapy useful in early pilot study (pouchitis)151 Budesonide (pouchitis)147 Antibiotics (pouchitis)140-146 [corrected]

Medical therapy for ulcerative colitis: The state of the art and beyond

Ulcerative colitis (UC) is an idiopathic inflammatory condition of the large intestine. Recent advances in our understanding of the pathogenesis of UC have led to the development of novel treatments for this often debilitating condition. Aside from aminosalicylates and corticosteroids, drugs that have been used for decades in the treatment of UC, biologic agents, in addition to medications targeting specific effector mechanisms involved in the inflammatory cascade, have been used in patients with UC with varying degrees of success. Clinicians have never had as many therapeutic options for UC as they do today. Herein we review the variety of treatment options, both standard and investigational, that are available for patients with UC.

Therapy of ulcerative colitis

The past year has brought forth several controversies regarding the treatment of ulcerative colitis along with several potentially important clinical advances. The aim of this review is to provide the practicing gastroenterologist with a summation of these recent developments, with particular emphasis on advances that have already moved toward acceptance into clinical practice. Controversies remain regarding the optimal formulations and doses of aminosalicylates. At the same time, the potential for chemoprotective effects in patients using maintenance therapy with mesalamine derivatives has been expanded. In addition, advances in biologic therapy for Crohn disease are beginning to be formally evaluated in ulcerative colitis, although the benefits of anti-tumor necrosis factor therapy in this condition remain to be established. Biologic therapies are beginning to be explored as adjunctive therapy for steroid-refractory ulcerative colitis, where trials of calcineurin inhibitors are also advancing clinical practice for this poor prognostic subgroup of patients. Finally, after surgery for ulcerative colitis, the treatment and prevention of pouchitis has become the one established indication for probiotic therapy. Despite some inroads into the medical therapy of ulcerative colitis, controversies remain regarding the optimal dosing and delivery systems of the most fundamental therapies, and how to optimize therapy for severe ulcerative colitis. Clinical research will continue to investigate new biologic agents that inhibit tumor necrosis factor and other pro-inflammatory cytokines, and ongoing trials with leukocyte apheresis are currently under way.

Medical therapy for ulcerative colitis 2004

There continue to be evolutionary changes in the management of ulcerative colitis despite the fact that, aside from a variety of aminosalicylate formulations, no new therapies have been approved over the past few decades. Nevertheless, debates continue regarding the optimization of treatment with aminosalicylates and the short- and long-term benefits of immunomodulation in ulcerative colitis. This article focuses on the most recent clinical studies pertaining to the management of ulcerative colitis and explores both the advances and controversies pertaining to aminosalicylate therapy, corticosteroids, cyclosporine, and the purine antimetabolites. Novel therapeutic approaches—including preliminary experience with biological therapies directed at tumor necrosis factor and other cytokines, adhesion molecules, growth factors, and probiotics—will be reviewed. Recent data regarding potential chemoprevention in long-standing ulcerative colitis and management of postoperative complications and pouchitis will also be discussed.

Evolving medical therapies for ulcerative colitis.

Therapies for patients with ulcerative colitis have, until recently, been limited in scope and efficacy. New formulations of mesalamine and corticosteroids have challenged the older therapies with respect to both efficacy and safety. The application of 6-mercaptopurine and azathioprine for steroid-refractory disease and maintenance of remission has resulted in studies of other candidate immunomodulatory agents. Biologic therapies targeting tumor necrosis factor, adhesion molecules, or other cytokines are under intense scrutiny as potential disease-altering agents that may even replace currently available products. Other approaches, including such wide-ranging products as heparin, nicotine, and probiotics, suggest that control of ulcerative colitis may require an individualized approach for each patient.

Update in Medical Therapy of Ulcerative Colitis

The bewildering array of medications in the therapy of inflammatory bowel disease (IBD) often confounds the clinician in the choice of specific agents regarding the balance between safety and efficacy. This review surveys and evaluates currently available IBD therapies as well as those used in clinical trials of ulcerative colitis. The primary purpose is to provide the busy clinician with a practical guide to the use of established and newly emerging medical therapies of IBD.

Medical therapy for ulcerative colitis

Although newer therapeutic agents are being developed for the treatment of inflammatory bowel disease, aminosalicylates and corticosteroids remain the mainstay of treatment for UC (Tables 2-5). Patients who do not respond to these agents or become steroid dependent require immunomodulatory therapy or curative surgery. Cyclosporine represents the greatest treatment advance for UC in 10 years. The role of nicotine, heparin, antibiotics, probiotics, and SCFA in the treatment of UC is less clear, but these agents may offer an alternative therapeutic approach for patients intolerant or nonresponsive to standard therapy.

Evolving medical therapies for ulcerative colitis.

Patients with ulcerative colitis have traditionally relied on sulfasalazine, mesalamine, and corticosteroids as the mainstay of medical therapy. Steroid-refractory, -dependent, or -intolerant patients have resorted to agents such as cyclosporine for short-term efficacy and 6-mercaptopurine or azathioprine for long-term efficacy. The next generation of evolving therapies includes many novel agents that target various aspects of the human immune response. Therapies that block the production or action of tumor necrosis factor have received much interest in inflammatory bowel disease. Treatments currently under study include interleukins, interferons, T-cell selective antibodies, molecules involved in cellular trafficking and signaling, mucosal healing or growth factors, and novel steroid agents. Other "less traditional" therapies, including probiotics, heparins, and anti-gastric ulcer remedies, challenge our understanding of the pathogenesis of ulcerative colitis and may provide further insights into future therapies.

Evolving treatment strategies for inflammatory bowel disease.

Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel diseases characterized by dysregulated intestinal immune responses in genetically susceptible hosts. Conventional approaches to the medical therapy of ulcerative colitis and Crohn's disease can now be directed at either induction or maintenance of remission to improve therapeutic efficacy while minimizing complications. Newer approaches have expanded the utility of conventional therapies by improving both safety and efficacy and highlight the importance of specific targets along the immunoinflammatory pathways. The combination of conventional and novel approaches now offers the potential of modifying the natural history of these diseases.

Medical therapies for ulcerative colitis and Crohn's disease.

This review focuses on data reported in the last year on medical treatment of Crohn's disease and ulcerative colitis. In Crohn's disease, a broad range of cytokine-based therapies are currently being tested. Although all are very exciting, the anti-tumor-necrosis-factor (TNF) approach remains the most effective, with infliximab (a chimeric monoclonal antibody directed against TNF) being the most active agent. With repeated infusions every 8 weeks, remission is induced and can be maintained even in refractory patients with no major apparent side effects. Thalidomide, an oral agent with anti-TNF effects, shows promise in non-controlled experience. Important new data on azathioprine/6-mercaptopurine (6-MP) and its metabolites are also helpful. Methotrexate can induce remissions in 6-MP-allergic or refractory Crohn's patients and has now shown efficacy as a maintenance agent. Beneficial effects are also reported for a variety of new agents: mycophenolate mofetil, tacrolimus (FK506), growth hormone, and granulocyte colony-stimulating factor (G-CSF). Important observations in ulcerative colitis (UC) over the past year include evidence of a protective effect of 5-aminosalicylic acid (5-ASA) with respect to colorectal cancer, negative results from a study for heparin monotherapy, and results from a comparison of mycophenolate mofetil versus azathioprine as maintenance therapy. Epidemiologically, the negative association between appendectomy and UC was corroborated in a meta-analysis, suggesting an immunologic role for this organ. Finally, in chronic pouchitis, probiotic therapy was found to maintain remissions very significantly.

Medical therapy for ulcerative colitis

Last year was not a banner year for developments in medical therapy for ulcerative colitis. In contrast to the expansion of therapies for Crohn disease, treatment for ulcerative colitis was evolutionary, at best, leading many patients to seek alternative medical approaches. Nevertheless, there have been advances in the application of aminosalicylates and immune modifiers for ulcerative colitis. Additional, nonconventional approaches include nicotine, probiotics, dietary therapies, and heparins. Several novel approaches have arisen from animal models, including additional means of inhibiting nuclear factor-kappaB and targeting of tumor necrosis factor-alpha.

Current medical therapy for ulcerative colitis.

In recent years, the advances in therapy of ulcera-tive colitis (UC) have been characterized mainly by the more extensive use of immunosuppression. Cy-closporin (CSA) may become a drug of choice to treat severe UC, but its long-term effect is insufficient. Topically, glucocorticosteroids (GCS) are hopeful in right ileocolonic UC, but no action for maintenance therapy[1-3]. The most significant development in recent years is the introduction of im-munomodulatory treatments using cytokines and an-ticytokines. Immunomodulation therapy creates great expectations since early reset of the immunos-tat might be able to control inflammation in a long term. Current treatment strategies are anti-inflam-matory and to modulate the immune response. Stan-dard therapies with sulphasalazine (SAS) or 5-aminosalicylic acids ( 5-ASA, mesalazine or mesalamine), GCS and antibiotics yield a fair im-mediate success, but long-term response to these therapies is poor. The greatest advance has been the introduction of immunosuppressive strategies. The indexes like the clinical activity index (CAI) proposed by Rachmilewitz[1], although useful, have not received general acknowledgement. Patients with an inflammatory bowel disease (IBD), such as UC or Crohn’s disease, have recur-rent symptoms with high morbidity. Mild disease requires only sympt omatic relief and dietary manipu-lation. Mild to moderate disease can be managed with 5-ASA, including olsalazine and mesalamine. Mesalamine enemas and suppositories are useful in treating proctosigmoiditis. Corticosteroids are beneficial in patients with more severe symptoms, but side effects limit their use, particularly for chronic therapy. Immunosuppressant therapy may be considered in patients with refractory disease that is not amenable to surgery. IBD in pregnant women can be managed with 5-ASA and corticosteroids[2]. Since longstanding IBD is associated with an increased risk of colon cancer, periodic colonoscopy is warranted. Since lesions in UC are quite diffuse and uniform endoscopic indexes used are quite straightfor-ward, clinical activity, endoscopic activity and his-tology show a reasonable correlation and it is useful to monitor disease activity also with flexible proc-tosigmoidoscopy. The persistence of active inflam-matory lesions at histology in the presence of endo-scopic remission predicts relapse. Bresci G et al[3] reported that the activity of the disease was evaluated by a Clinical Activity Index and an Endoscopic Index. Of 112 cases of UC observed, 95 showed no change in extent and were studied as examples of non-progressive UC, and in this group the extension of the disease was: pancolitis in 19%, left sided col-itis in 39%, proctosigmoiditis in 17% and proctitis in 25%. A colectomy had to be performed in 5%. None of the enrolled cases developed a cancer dur-ing the follow up. The patients with ulcerative pancolitis or left-sided colitis were treated with 5-ASA-1.6g/d in a delayed-release formulation, while the patients with proctosigmoiditis or proctitis were treated with 5-ASA enem as 4 g/d. The patients with more than one relapse/ year accounted for 39%. The proportion of patients with only one relapse/ year was 53%. The patients with steady re-mission for all the seven years of the trial were only 8%, but with a statistically significant difference between the groups with initial diagnosis of proc-tosigmoiditis or proctitis and the group with initial diagnosis of pancolitis or left-sided colitis (12% vs 5%). Among the patients with continuous remis-sion, 37% showed colonic alterations, with an en-doscopic score higher than 4 but a clinical score less than 6. Side effects were observed in 6% of patients but without treatment withdrawal. Non-progressive UC throughout the colon has a relatively good prog-nosis, which seems to be independent of the location of the disease, even if Bresci G et al[3] have found a statistically significant higher percentage of patients with steady remission among the patients with more distal diseases.

Cytokines and mechanisms of action of glucocorticoids and aminosalicylates in the treatment of ulcerative colitis and Crohn's disease.

Medical therapy of ulcerative colitis and Crohn's disease involves the control of active inflammation to obtain clinical remission and then maintaining that remission. Corticosteroids and 5-aminosalicylic acid are the mainstay of such management. Both have a wide range of properties and are able to inhibit many effector mechanisms which are potentially involved in mucosal inflammation. In in vitro assays, both are able to inhibit the release of a wide variety of pro-inflammatory and immunoregulatory cytokines. In vivo, such effects would limit tissue damage, prevent further amplification of the immune response and restore epithelial function.

A successful case of intraarterial prednisolone injection therapy in severe ulcerative colitis unresponsive to an intensive intravenous regimen

A successful case of intraarterial prednisolone injection therapy in severe ulcerative colitis unresponsive to conventional therapy, including an intensive intravenous regimen, is presented. After the direct administration of prednisolone into the mesenteric arteries, the patient's conditions markedly improved, and he succeeded in overcoming the acute stage and entered remission. Accordingly, he safely underwent elective surgery which was finally required because of the inability to withdraw prednisolone therapy. It is well worthwhile to consider this therapy in the last resort of medical therapy for ulcerative colitis.

Medical therapy of ulcerative colitis

Medical therapy of ulcerative colitis