Active Distal Ulcerative Colitis Research Articles

Propensity score analysis the clinical characteristics of active distal and extensive ulcerative colitis: a retrospective study.

Background and Objectives: Ulcerative Colitis (UC) subtypes defined by disease extent and shared pathophysiology are important. Analyzing the clinical characteristics of UC with different disease extent and optimizing clinical typing are conducive to the pathogenesis research, disease monitoring and precise treatment. Methods: 188 patients with active UC were divided into distal and extensive colitis. The clinical characteristics of the two groups were analyzed by propensity score. Spearman is used for correlation analysis, and receiver operating characteristic (ROC) curve was used to evaluate the ability of clinical indicators to predict Mayo endoscopic subscore (MES). Results: Compared with distal colitis, extensive colitis had more severe disease activity, younger age, higher utilization rate of corticosteroids and incidence of extra intestinal manifestations (EIMs), and clinical indicators were differentially expressed in the two groups. After using propensity score, the incidence of EIMs in the extensive colitis was still higher than that in distal colitis. Inflammation, coagulation and immune indicators like CRP, FC, IL-10, D-D and α1-MG are higher in extensive colitis, and metabolic indicators like LDL-C, HDL-C, TC, GSP and albumin are higher in distal colitis. The correlation between clinical indicators and MES is affected by disease extent. The area under curve (AUC) of CRP + D-D + α2-MG for predicting distal colitis MES3 was 0.85, and the AUC of IL-6+ GSP+ α1-MG predicted extensive colitis MES3 can reach 0.82. Conclusion: Differential clinical indicators can become potential markers for predicting disease progression and prognosis, and have significance for UC mechanism research and drug development. We can select biomarkers according to lesion site.

Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6.

Hyaluronan (HA) has proven to be beneficial in the treatment of several diseases. Recently, it has been shown that the local application of HA (IBD98E) improves endoscopic and clinical outcomes in subjects with active distal ulcerative colitis (UC). However, the mechanisms by which this polysaccharide exerts its beneficial effects are unclear. Here, we demonstrated that HA treatment in vitro and in vivo improved mucosal healing by accelerating intestinal epithelial regeneration. Indeed, mice treated with HA showed a faster recovery from colitis and reduced endoscopic signs of mucosal inflammation compared to those receiving saline. Furthermore, histological analysis revealed less ulcerated mucosa in mice treated with HA, characterized by re-epithelialized areas. TSG-6, the secreted product of TNF-stimulated gene-6, is an HA-binding protein shown previously to have tissue-protective properties and promote wound healing. Mucosal levels of TSG-6 increased in UC patients compared to the healthy controls and also after wounding in mice. TSG-6 deletion prevented the beneficial properties of HA in mucosal wound repair, suggesting that the interaction of HA with TSG-6 is crucial for intestinal epithelial regeneration. Overall these results are consistent with HA having a therapeutic effect via the promotion of mucosal healing in patients with ulcerative colitis.

Efficacy and safety of rectal 5-aminosalicylic acid versus corticosteroids in active distal ulcerative colitis: a systematic review and network meta-analysis

Topical 5-aminosalicylic acid (5-ASA) and corticosteroids are used frequently in the treatment of active distal ulcerative colitis (UC). Our study aimed to determine the efficacy and safety of different topical drugs used to treat active distal UC. A random-effects model within a Bayesian framework was utilized to compare treatment effects and safety as odds ratios (ORs) with corresponding 95% credible intervals (CrI). The surface under the cumulative ranking area (SUCRA) and median rank (MR) with corresponding 95% CrI were calculated to rank the treatment outcomes. In the induction of clinical and endoscopic remission, most regimens showed significant advantages over placebo except topical budesonide 0.5 mg/d and hydrocortisone 100 mg/d. According to SUCRA and MR values, rectal 5-ASA 1.5 to 2.0 g/d + Beclomethasone dipropionate (BDP) 3 mg/d rendered the highest probability of being the best regimen to achieve clinical and endoscopic remission, followed by the separate use of 5-ASA 4 g/d and BDP 3 mg/d. The occurrence of adverse events was not significantly different between each treatments and placebo. In conclusion, the combined use of topical 5-ASA and BDP proved to be the best choice for active distal UC and further well-designed researches are warranted to assess its efficacy and safety.

Su1891 - Efficacy and Safety of Topical 5-Aminosalicylic Acid and Corticosteroids in Active Distal Ulcerative Colitis: A Systematic Review and Network Meta-Analysis

Su1891 - Efficacy and Safety of Topical 5-Aminosalicylic Acid and Corticosteroids in Active Distal Ulcerative Colitis: A Systematic Review and Network Meta-Analysis

Analysis of the Safety and Tolerability of Cyclical Dosing of Budesonide Foam for the Treatment of Distal Ulcerative Colitis

Introduction: Rectal budesonide foam, a second-generation corticosteroid with high first-pass hepatic metabolism, is indicated for induction of remission of mild to moderate distal ulcerative colitis (UC). This study prospectively assessed long-term tolerability of cyclically dosed budesonide foam. Methods: Adults with active distal UC (ulcerative proctitis or ulcerative proctosigmoiditis extending ≤40 cm from the anal verge) who previously participated in budesonide foam clinical trials received 6-week cycles of open-label budesonide foam: 2 mg/25 mL twice daily (BID) for 2 weeks, then once daily (QD) for 4 weeks as needed to manage disease flares. Cycles were separated by ≥48 hours. Safety assessments included periodic fasting blood chemistries, serum cortisol levels, and recording of adverse events (AEs) through 1 week post-treatment. Results: 114 patients received cycle 1, 65 cycle 2, and 41, 22, 12, 5, 3, and 1 patient received cycles 3-8, respectively. The mean duration of exposure for all patients was 92 days (range, 10-335 days). At baseline, mean modified Mayo Disease Activity Index [MMDAI] score was 7.2; 57.9% of patients had moderate distal UC (MMDAI score, 7-10). Mean treatment compliance was ≥90.5% for all 8 treatment cycles. Overall, 57.9% of patients had AEs, the most frequent of which were decreased blood cortisol concentration (17.5% [11.4% considered drug-related]), abdominal pain (7.9%), and headache (7.0%). Most AEs (experienced by 90.9% of patients) were mild or moderate in intensity, and their frequency was similar across cycles with the largest populations (cycle 1 [43.0%], 2 [43.1%], and 3 [41.5%]). No serious AEs were observed. Of the 17 patients (14.9%) who withdrew from the study because of an AE, 8 (7.0%) withdrew due to decreased blood cortisol concentrations. Mean morning serum cortisol concentrations decreased from baseline to day 15 (end of BID dosing; range, -87.8 to -25.5 nmol/L), but recovered at week 6 (end of QD dosing; range, -10.4 to 0.9 nmol/L), during cycles with >15 patients (cycles 1-4). Normal (≥138 nmol/L) morning serum cortisol concentrations were observed in ≥75% of patients at day 15 and ≥83.9% at week 6 for all treatment cycles. No clinically relevant changes in vital signs and physical exam findings were observed. Conclusion: Multiple repeat treatments with cyclically dosed rectal budesonide foam were well tolerated by patients with distal UC flares. Funded by Salix Pharmaceuticals.

Casein glycomacropeptide for active distal ulcerative colitis: a randomized pilot study.

In ulcerative colitis (UC), dietary supplements may have anti-inflammatory properties and improve disease course. We investigated the effects of casein glycomacropeptide (CGMP), a fraction of bovine whey protein, in active UC. In a randomized open-label intervention study, 24 patients with active UC involving 10-40cm of the distal colon were randomized in a 2:1 ratio into two groups. The first group was administered their usual treatment plus a daily supplement of CGMP 30g, and the second group was administered a dose escalation to 4800mg oral mesalamine daily (standard treatment) for 4weeks. Clinical, endoscopic, mucosal and circulating disease activity markers were monitored. Acceptance of and adherence to CGMP up to 8weeks were documented. After 4weeks of treatment, 10 of 16 (63%) patients who received CGMP had an unchanged or decreased Simple Clinical Colitis Activity Index (SCCAI), which was similar to the four of eight (50%) (P=0·67) patients on the standard treatment. The number of patients in which SCCAI decreased by three or more did not differ between the two groups: nine of 16 (56%) in the CGMP group vs. four of eight (50%) in the standard treatment group (P=0·77). Changes in disease extent and severity were similar between the two groups. CGMP was well tolerated and accepted by the patients. The addition of CGMP as a nutritional therapy to standard treatment was safe and accepted by patients with active distal UC. The disease-modifying effect of CGMP was similar to that of the mesalamine dose escalation.

Rectal budesonide and mesalamine formulations in active ulcerative proctosigmoiditis: efficacy, tolerance, and treatment approach.

Ulcerative colitis (UC) is an immune-mediated disease of the colon that is characterized by diffuse and continuous inflammation contiguous from the rectum. Half of UC patients have inflammation limited to the distal colon (proctitis or proctosigmoiditis) that primarily causes symptoms of bloody diarrhea and urgency. Mild-to-moderate distal UC can be effectively treated with topical formulations (rectal suppositories, enemas, or foam) of mesalamine or steroids to reduce mucosal inflammation and alleviate symptoms. Enemas or foam formulations adequately reach up to the splenic flexure, have a minimal side-effect profile, and induce remission alone or in combination with systemic immunosuppressive therapy. Herein, we compare the efficacy, cost, patient tolerance, and side-effect profiles of steroid and mesalamine rectal formulations in distal UC. Patients with distal mild-to-moderate UC have a remission rate of approximately 75% (NNT =2) after treatment for 6 weeks with mesalamine enemas. Rectal budesonide foam induces remission in 41.2% of patients with mild-to-moderate active distal UC compared to 24% of patient treated with placebo (NNT =5). However, rectal budesonide has better patient tolerance profile compared to enema formulations. Despite its favorable efficacy, safety, and cost profiles, patients and physicians significantly underuse topical treatments for treating distal colitis. This necessitates improved patient education and physician familiarity regarding the indications, effectiveness, and potential financial and tolerability barriers in using rectal formulations.

Recent advances in inflammatory bowel disease.

Recent advances in inflammatory bowel disease.

Intravesical Application of Rebamipide Promotes Urothelial Healing in a Rat Cystitis Model

Rebamipide is used as a topical therapeutic agent for various organs. We examined the healing effects of intravesical rebamipide on damaged urothelium in a rat model of chemically induced cystitis. Hydrochloride was injected in the bladder of female Sprague Dawley® rats to induce cystitis. On days 1 and 4 rebamipide (1 or 10mM) or vehicle was administered in the bladder and maintained for 1 hour. Histopathology, urothelial permeability, cystometrogram and nociceptive behaviors were evaluated on day 7. Also, tissue rebamipide concentrations after the 1-hour bladder instillation were quantified using high performance liquid chromatography. Intravesically administered rebamipide permeated the bladder, particularly in hydrochloride treated rats, and the pharmacologically effective tissue dose remained for greater than 6 hours. Bladder histological evaluation revealed polymorphological inflammatory cell infiltration and decreased positive staining for uroplakin 3A in hydrochloride treated rats. Scanning electron microscopy showed damaged tight junctions in the hydrochloride group. Evans blue absorption in the bladder wall was increased in hydrochloride treated rats. These findings, which were associated with urothelial injury and increased permeability, were dependently suppressed by the rebamipide treatment dose. Cystometrogram demonstrated that the intercontraction interval was shorter in hydrochloride treated rats but prolonged by rebamipide. The increased nociceptive behaviors observed after intravesical resiniferatoxin administration werealso suppressed by rebamipide. Intravesical rebamipide accelerated the repair of damaged urothelium, protected urothelial barrier function and suppressed bladder overactivity and nociception.

Safety and efficacy of sodium hyaluronate (IBD98E) in the induction of clinical and endoscopic remission in subjects with distal ulcerative colitis

Sodium hyaluronate can contribute to the hydration and maintenance of the integrity of the intestinal mucosa. Restoration of the protective layer with sodium hyaluronate may contribute to the induction of remission of active ulcerative colitis. We investigated the safety and efficacy of sodium hyaluronate enema (IBD98E) in distal active ulcerative colitis, in a prospective, uncontrolled, open-label pilot trial. Subjects with active distal ulcerative colitis (UCDAI ≥ 4 and sigmoidoscopy score ≥ 1) received IBD98E 60 mL enema once a day. Primary endpoints were safety and clinical response rate at Day 28. Secondary endpoints included clinical remission, endoscopic remission, and tolerability of IBD98E. Paired Student's t-test was performed to assess statistically significant differences in subjects between baseline and Day 28. Twenty-one subjects were enrolled. The overall safety profile was good; no serious adverse events were recorded. At Day 28, 9 subjects (42.9%) were clinical responders, and 10 subjects (47.6%) had an endoscopic response. Eight subjects (38.1%) achieved clinical remission, and 10 subjects (47.6%) achieved endoscopic remission. The mean average UCDAI score decreased from 6.10 to 3.81 at Day 28 (p=0.001), and average endoscopic score decreased from 1.57 to 1.10 (p=0.004). IBD98E seems to be safe and effective for the induction of clinical and endoscopic remission. Placebo-controlled studies are warranted.

Intravesical Application of Rebamipide Suppresses Bladder Inflammation in a Rat Cystitis Model

We examined the effects of intravesical application of rebamipide (Otsuka Pharmaceutical, Tokyo, Japan) on bladder inflammation and overactivity in a chemically induced cystitis model. Female Sprague Dawley® rats under isoflurane anesthesia were injected with 150 mg/kg cyclophosphamide in the peritoneum, and 1 mM or 10 mM rebamipide or vehicle was administered in the bladder and remained for 1 hour. Control rats were injected with saline in the peritoneum and vehicle was administered in the bladder. The bladder was harvested at 48 hours. Hematoxylin and eosin staining was performed and the inflammation grade was assessed. The amount of myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proinflammatory cytokines were quantified using reverse transcriptase-polymerase chain reaction. Cystometrogram was done in awake rats 48 hours after cyclophosphamide treatment to measure voiding reflex parameters. Histological evaluation revealed that bladder inflammation in cyclophosphamide treated rats was suppressed by rebamipide in a dose dependent manner. Up-regulated myeloperoxidase, IL-1β, IL-6 and TNF-α expression in cyclophosphamide treated rats was also suppressed in rebamipide treated rats. Cystometrogram demonstrated that the intercontraction interval decreased in cyclophosphamide treated rats but was prolonged by rebamipide. Intravesical application of rebamipide suppressed bladder inflammation and overactivity in a dose dependent manner. This may provide a new treatment strategy for chemotherapy associated cystitis.

Rectal 5-aminosalicylic acid for maintenance of remission in ulcerative colitis

Rectal 5-aminosalicylic acid for maintenance of remission in ulcerative colitis

Medical management of ulcerative colitis with a specific focus on 5-aminosalicylates.

Medical management of ulcerative colitis has continued to evolve over more than half of a century. Perhaps, the important advance was the development of sulfasalazine, a drug initially used for the treatment of inflammatory joint disease and only later in the treatment of inflammatory bowel disease. Sulfasalazine was a combination designer drug consisting of sulfapyridine, a sulfa-containing antibacterial agent, and 5-amino-salicylate (5-ASA), an anti-inflammatory agent. Its value appeared to be its ability to target a therapeutic concentration of the 5-ASA component of the medication primarily in the colon, largely avoiding proximal small intestinal absorption. With increasing experience, however, it also became evident that many patients treated with sulfasalazine developed intolerance to the drug and, in some rare instances, serious drug-induced hypersensitivity reactions, largely to the sulfapyridine portion. As a result, a number of alternative forms of delivery of 5-ASA were developed consisting of either a similar sulfasalazine-like prodrug formulation requiring luminal destruction of an azo-bond releasing the 5-ASA or a pH-dependent 5-ASA packaging system that permitted release in the distal intestine, particularly in the colon. As a result, 5-ASA—containing medications continue to provide a valuable management tool for remission induction in mildly to moderately active distal or extensive ulcerative colitis, an additional option for more severely symptomatic disease and value for maintenance therapy with limited potential side effects, even with long-term use.

Randomised clinical trial: the effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis

Intestinal microbiota manipulation, one of the pathogenetic components of inflammatory bowel disease (IBD), has become an attractive therapy for ulcerative colitis (UC). To assess in children with active distal UC the effectiveness of Lactobacillus (L) reuteri ATCC 55730 enema on inflammation and cytokine expression of rectal mucosa. A total of 40 patients (median age: 7.2 years range 6-18) with mild to moderate UC were enrolled in a prospective, randomised, placebo-controlled study. They received an enema solution containing 10(10) CFU of L. reuteri ATCC 55730 or placebo for 8 weeks, in addition to oral mesalazine. Clinical endoscopic and histological scores as well as rectal mucosal expression levels of IL-10, IL-1β, TNFα and IL-8 were evaluated at the beginning and at the end of the trial. Thirty-one patients accomplished the trial (17 males, median age 13 year, range 7-18). Mayo score (including clinical and endoscopic features) decreased significantly in the L. reuteri group (3.2 ± 1.3 vs. 8.6 ± 0.8, P < 0.01) compared with placebo (7.1 ± 1.1 vs. 8.7 ± 0.7, NS); furthermore, histological score significantly decrease only in the L. reuteri group (0.6 ± 0.5 vs. 4.5 ± 0.6, P < 0.01) (placebo: 2.9 ± 0.8 vs. 4.6 ± 0.6, NS). At the post-trial evaluation of cytokine mucosal expression levels, IL-10 significantly increased (P < 0.01) whereas IL-1β, TNFα and IL-8 significantly decreased (P < 0.01) only in the L. reuteri group. In children with active distal ulcerative colitis, rectal infusion of L. reuteri is effective in improving mucosal inflammation and changing mucosal expression levels of some cytokines involved in the mechanisms of inflammatory bowel disease.

Factors Predicting Bleeding Cessation, Mucosal Healing and Clinical Remission in Patients Receiving Topical Mesalamine with Active Distal Ulcerative Colitis

Factors Predicting Bleeding Cessation, Mucosal Healing and Clinical Remission in Patients Receiving Topical Mesalamine with Active Distal Ulcerative Colitis

Early symptomatic response and mucosal healing with mesalazine rectal suspension therapy in active distal ulcerative colitis - additional results from two controlled studies

Rapid resolution of symptoms and endoscopic inflammation in ulcerative colitis (UC) represent important treatment goals. To establish times to bleeding cessation and endoscopic healing for topical and oral mesalazine in active distal UC, a post hoc analysis of two published studies was performed. Study I (Sutherland 1987) compared mesalazine rectal suspension to placebo, while Study II (Safdi 1997) compared topical suspensions, either alone or in combination with oral mesalazine, and oral alone. Cessation of rectal bleeding (RB) was defined as absence of bleeding on four consecutive days. Endoscopic remission was defined as DAI mucosal healing (MH) subscore=0 and clinical remission as MH subscore =0-1 and ≥ 1-point improvement, plus RB subscore = 0. Study I: By Day 2, 31.4% of subjects using topical monotherapy reported no RB vs. 5.5% in the placebo arm (P<0.0006); median time to RB cessation was 8 days. Significantly higher rates of endoscopic (25.0% vs. 7.8%, P<0.005) and clinical remission (48.6% vs. 9.6%, P<0.0001) were observed at Week 3. Study II: A significantly higher proportion of subjects achieved RB cessation with combination therapy vs. oral therapy, commencing by Day 8. By Week 3, a significantly higher proportion of subjects using combination therapy achieved clinical remission compared to oral therapy alone (57.9% vs. 18.2%, P<0.05). Topical mesalazine suspension, either alone or in combination with oral mesalazine, led to earlier rectal bleeding cessation and mucosal healing. These data support use of topical therapy for more rapid treatment benefit in active distal ulcerative colitis.

Early Symptomatic Response and Mucosal Healing With Mesalamine Rectal Suspension Therapy in the Treatment of Active Distal Ulcerative Colitis (UC): Additional Results From Two Controlled, Randomized Trials

Early Symptomatic Response and Mucosal Healing With Mesalamine Rectal Suspension Therapy in the Treatment of Active Distal Ulcerative Colitis (UC): Additional Results From Two Controlled, Randomized Trials

Rectal 5-aminosalicylic acid for induction of remission in ulcerative colitis

5-Aminosalicylates (5-ASA) are considered a first-line therapy for inducing and maintaining remission of mild to moderately active ulcerative colitis (UC). When inflammation in UC is limited to the distal colon, 5-ASA can also be administered rectally as a suppository, enema or foam. A systematic review was undertaken to evaluate the efficacy of rectal 5-ASA for treating active distal UC. Electronic searches of the MEDLINE database (1966-2008), the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD Group Specialized Trials Register were supplemented by manual reviews of reference listings and conference proceedings. Randomized trials comparing rectal 5-ASA to placebo or another active therapy were eligible for inclusion. Eligible trials enrolled patients with a distal disease margin less than 60 cm from the anal verge or distal to the splenic flexure. Trials that enrolled subjects less than 12 years of age were excluded. Eligibility was assessed by three authors. Data were extracted by two authors using standardized forms. Pooled odds ratios (POR) for inducing improvement and remission by symptomatic, endoscopic and histologic criteria were calculated using an intention to treat principle. Fixed effects models were used unless heterogeneity was encountered within groups (P < 0.10), where random effects models were used. All statistical analyses were performed using RevMan 5. Where sufficient data were available, subgroup analyses were performed for disease extent, total daily 5-ASA dose, 5-ASA formulation (enema,suppository, foam) and the type of control intervention (placebo or another active therapy). Thirty-eight studies fulfilled the inclusion criteria. Rectal 5-ASA was superior to placebo for inducing symptomatic, endoscopic and histological improvement and remission, with POR for symptomatic improvement 8.87 (8 trials, 95% CI: 5.30 to 14.83; P < 0.00001), endoscopic improvement 11.18 (5 trials, 95% CI 5.99 to 20.88; P < 0.00001), histologic improvement 7.69 (6 trials, 95% CI 3.26 to 18.12; P < 0.00001), symptomatic remission 8.30 (8 trials, 95% CI 4.28 to 16.12; P < 0.00001), endoscopic remission 5.31 (7 trials, 95% CI 3.15 to 8.92; P < 0.00001), and histologic remission 6.28 (5 trials, 95% CI 2.74 to 14.40; P < 0.0001). Rectal 5-ASA was superior to rectal corticosteroids for inducing symptomatic improvement and remission with POR 1.56 (6 trials, 95% CI 1.15 to 2.11; P = 0.004) and 1.65 (6 trials, 95% CI 1.11 to 2.45; P = 0.01), respectively. Rectal 5-ASA was not superior to oral 5-ASA for symptomatic improvement (POR 2.25; 95% CI 0.53 to 19.54; P = 0.27). Neither total daily dose nor 5-ASA formulation affected treatment response. Rectal 5-ASA should be considered a first-line therapy for patients with mild to moderately active distal UC. The optimal total daily dose and dose frequency of 5-ASA remain to be determined. Future research should define differences in efficacy among patient subgroups defined by proximal disease margin and disease activity. There is a strong need for consensus standardization of outcome measurements for clinical trials in ulcerative colitis.

Topical Rosiglitazone Treatment Improves Ulcerative Colitis by Restoring Peroxisome Proliferator-Activated Receptor-γ Activity

Impaired epithelial expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) has been described in animal colitis models and briefly in patients with ulcerative colitis, but the functional significance in humans is not well defined. We examined PPARgamma expression and functional activity in human colonic epithelium and explored the potential of topical treatment with rosiglitazone (a PPARgamma ligand) in patients with ulcerative colitis. Spontaneous and rosiglitazone-mediated PPARgamma and adipophillin expression (a gene transcriptionally activated by PPARgamma) were measured by reverse transcriptase PCR in colonic biopsies and isolated epithelial cells from patients with ulcerative colitis and controls. Fourteen patients with active distal ulcerative colitis were randomized to either rosiglitazone (4 mg) or mesalazine (1 g) enema treatment once daily for 14 days. PPARgamma expression was fourfold reduced in epithelial cells from inflamed compared with uninflamed mucosa and controls. Adipophillin levels were decreased in parallel. Rosiglitazone induced a concentration-dependent increase in adipophillin levels and restored PPARgamma activity in epithelial cells from inflamed mucosa in vitro. Rosiglitazone enema treatment was well tolerated and reduced the Mayo ulcerative colitis score from 8.9 to 4.3 (P<0.01), similar to the effect of mesalazine. Rosiglitazone increased adipophillin levels in the epithelial cells of the patients, indicating PPARgamma activation in vivo. Roziglitasone enemas improve impaired PPARgamma activity in inflamed colonic epithelium and have beneficial clinical effect in patients with active distal ulcerative colitis. These findings raise interest in further studies of PPARgamma ligands that exhibit their anti-inflammatory effect locally in the gut to avoid possible systemic side effects.

Recent advances in the management of distal ulcerative colitis

The most frequent localization of ulcerative colitis (UC) is the distal colon. In treating patients with active distal UC, efficacy and targeting of the drug to the distal colon are key priorities. Oral and rectal 5-aminosalicylic acid (5-ASA) preparations represent the first line therapy of mild-to-moderate distal UC for both induction and maintenance treatment. It has been reported that many UC patients are not adherent to therapy and that non-compliant patients had a 5-fold risk of experiencing a relapse. These findings led to the introduction of once-daily oral regimens of 5-ASA as better therapeutic options in clinical practice due to improved adherence. New formulations of mesalazine, including the multi-matrix delivery system, and mesalazine granules, which allow once-daily administration, have been developed. They have been demonstrated to be efficacious in inducing and maintaining remission in mild-to-moderate distal UC in large clinical trials. However, existing data for distal UC are rather insufficient to make a comparison between new and classical 5-ASA formulations. It seems that the new formulations are at least as effective as classical oral 5-ASA formulations. Other treatment options, in the case that 5-ASA therapy is not effective, include systemic corticosteroids, thiopurines (azathioprine or 6-mercaptopurine), cyclosporine, infliximab and surgery. The combination of a prompt diagnostic work-up, a correct therapeutic approach and an appropriate follow-up schedule is important in the management of patients with distal UC. This approach can shorten the duration of symptoms, induce a prolonged remission, improve patient's quality of life, and optimize the use of health resources.