Speaker: Massimo D’Amato, MD, Senior Investigator, Clinical Pharmacology, Rotta Research Laboratories, Monza, Italy
The cholecystokinin (CCK) receptor antagonist dexloxiglu-mide (Rotta Research Laboratories/Forest Laboratories) might be a novel therapeutic agent for the treatment of constipation-predominant irritable bowel syndrome (C-IBS) in female patients, having demonstrated its effectiveness in relieving IBS symptoms, and because it is well-tolerated.
Because CCK might play a role in the pathogenesis of IBS, as a result of its involvement in the modulation of GI visceral sensory and motor responses, a study was designed to assess the safety and efficacy of the selective CCK receptor antagonist dexloxiglu-mide. A total of 405 patients (328 females, 77 males) with IBS were randomized to receive either dexloxiglumide 200 mg three times daily (202 patients) or placebo (203 patients) for 12 weeks, in a randomized, double-blind, parallel-group clinical trial. Prior to randomization, patients were stratified to IBS subgroups according to their bowel habit predominance: alternating-134 patients; diarrhea-113 patients; constipation-126 patients. At the end of the treatment period or at early termination, patients rate their response as much better to better (improved), no change, or much worse (not improved). Responders, according to a validated Global Improvement Assessment (GIA), were those patients who judged themselves improved and had a decrease in mean abdominal pain during the last two weeks of treatment compared to baseline.
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The proportion of responders with dexloxiglumide was higher than with placebo in the patient population as a whole (39% vs. 34%). This improvement reached statistical significance in the subgroup of female patients with C-IBS (dexloxiglumide, 40% vs. placebo, 22%). In addition, actively treated female C-IBS patients reported significantly reduced abdominal pain or discomfort; improved straining, incomplete evacuations, and global well-being; and they had more pain-free and bloating-free days.
Locally Active Corticosteroid for Crohn’s Disease
Speaker: Sunanda Kane, MD, Assistant Professor of Medicine, University of Chicago Medical Center, Chicago, Illinois
A systematic review and meta-analysis of selected clinical trials reveals that budesonide modified release capsules (MRC) (Ento-cort, EC), a synthetic locally active glucocorticosteroid, at a 9-mg dose, has been shown to be more active than the commonly used 5-acetylsalicylic acid product mesalamine or placebo for inducing remission in patients with mild to moderate active Crohn’s disease and can be used as first-line treatment. Also, while equivalent in action with conventional corticosteroids, budesonide MRC is markedly less likely to cause corticosteroid-associated adverse events than conventional steroids like prednisolone. buy kamagra oral jelly
The meta-analysis was carried out on approximately 1,000 patients with mild to moderate active Crohn’s disease of the ileum and/or ascending colon enrolled in five randomized control trials comparing either the safety and efficacy of mesalamine (one study), placebo (two studies), or prednisolone (two studies). The trials reported on the effectiveness of treatment, defined as decreasing or maintaining Crohn’s Disease Activity Index (CDAI) scores of 150 points or less, and on adverse event data.
The main results showed that budesonide MRC was more likely to induce remission of mild to moderately active Crohn’s disease than placebo (relative risk [RR]=1.82) or mesalamine (RR=1.73), with no significant difference in inducing remission between budesonide MRC and prednisolone. Budesonide, however, was less likely to cause corticosteroid-related adverse events than prednisolone (RR=0.65).
Monoclonal Antibody for Crohn’s Disease
Speaker: Gary R. Lichtenstein, MD, Associate Professor of Medicine and Director of the Center for Inflammatory Bowel Disease, Hospital of the University of Pennsylvania and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Data from the ACCENT I (A Chronic Clinical Trial Evaluating Infliximab in a New Long-Term Treatment Regimen demonstrated that infliximab (Remicade, Centecor) maintenance therapy in corticosteroid-dependent Crohn’s disease (CD) patients makes it possible for these individuals to reduce or discontinue corticos-teroid use, while maintaining disease remission.
Although the ACCENT I study was designed to determine whether maintenance dosing with infliximab could prolong disease progression, after six weeks in the trial, patients who were on corticosteroids at baseline and had a clinical response at week 2 were allowed to taper their corticosteroid doses by 5 mg per week if their baseline doses were 20 mg daily or more of prednisolone or equivalent, or 2.5 mg per week if their baseline doses were less than 20 mg daily.
Initially, 573 CD patients were enrolled in the trial and 335 persons were included in the efficacy analysis to be carried out at 30 and 54 weeks. Some 52.2% of week-2 responders were receiving corticosteroids at baseline, with a median dose of 20 mg daily. At week 30, the period of these reported data, the median dose of corticosteroids was 10 mg daily in the placebo maintenance group and 0 mg daily in the two infliximab maintenance groups (5 mg daily and 10 mg daily). In addition, approximately three times as many patients in the infliximab maintenance groups were able to discontinue corticosteroids while maintaining clinical remission as compared to those who received a single dose of infliximab 5 mg for induction, followed by placebo maintenance. This included 10.7% of placebo maintenance patients, 31% of 5-mg daily maintenance patients, and 36.8% of 10-mg daily maintenance patients. This benefit was seen whether patients had been on corticosteroids for less than a year or more than a year before entering the study.