Uma K. Murthy

Postpolypectomy bleeding in patients undergoing colonoscopy on uninterrupted clopidogrel therapy

BACKGROUND The risk of postpolypectomy bleeding (PPB) in patients undergoing colonoscopy on uninterrupted clopidogrel therapy has not been established. OBJECTIVE To assess the PPB rate and outcome and identify risk factors associated with PPB in patients taking clopidogrel. DESIGN Single-center, retrospective study. Demographics, clinical parameters, polyp characteristics, polypectomy techniques, and postpolypectomy events in the groups were compared by univariate analysis. Stepwise logistic regression analyses identified independent risk factors associated with PPB. SETTING Veterans Affairs Medical Center. PATIENTS A total of 142 patients (375 polypectomies) taking clopidogrel (cases) and 1243 patients (3226 polypectomies) not taking clopidogrel (controls). INTERVENTIONS None. MAIN OUTCOME MEASUREMENTS Postpolypectomy bleeding, hospitalization, and mortality. RESULTS The immediate (intraprocedural) bleeding rate was similar in the 2 groups (2.1% vs 2.1%). Delayed (postprocedural) PPB rate was higher in the group taking clopidogrel (3.5% vs 1.0%, P = .02). Delayed bleeding of significance requiring hospitalization and transfusion/intervention was also higher in patients taking clopidogrel (2.1% vs 0.4%, P = .04). The length of hospital stay and interventions for PPB were comparable between the 2 groups. There was no mortality. Concomitant use of clopidogrel and aspirin/other nonsteroidal anti-inflammatory drugs (odds ratio 3.7; 95% CI, 1.6-8.5) and the number of polyps removed (OR 1.3; 95% CI, 1.2-1.4) were the only significant risk factors associated with PPB. Clopidogrel alone was not an independent risk factor for PPB. LIMITATIONS Retrospective study and small number of patients with PPB. CONCLUSIONS The PPB rate is significantly higher in patients undergoing polypectomy while taking clopidogrel and concomitant aspirin/nonsteroidal anti-inflammatory drugs; however, the risk is small and the outcome is favorable. Routine cessation of clopidogrel in patients before colonoscopy/polypectomy is not necessary.

Outcome of Retinopathy in Chronic Hepatitis C Patients Treated with Peginterferon and Ribavirin

The purpose of this study is to evaluate the incidence and outcome of retinopathy in chronic hepatitis C patients treated with peginterferon and ribavirin. A total of 74 hepatitis C patients with baseline eye exams and eye exams during therapy were included. Retinopathy was defined as development of cotton wool spots and/or intra-retinal hemorrhage. Demographics, hepatitis C viral characteristics, treatment and laboratory data, and eye exam findings were compared in groups with and without retinopathy. Retinopathy developed in 28 (38%), early in therapy. Pre-treatment eye exams did not predict risk of retinopathy. Therapy was continued in all but one; cotton wool spots resolved in 24 of 26. All nine patients with intra-retinal hemorrhage had resolution. No patient had retinopathy-related visual deterioration. Retinopathy is common with peginterferon therapy, but the outcome is favorable. Cessation of therapy for retinopathy is not warranted. Severe visual disturbances and scotomas deserve further evaluation.

T1202 Once-Daily Mesalamine Granules Effectively Maintain Remission from Ulcerative Colitis: Data from 2 Phase 3 Trials

Mesalamine granules (MG) are the first 5-aminosalicylate (5-ASA) formulation to use an innovative delivery system that combines delayedand extended-release mechanisms to release mesalamine directly in the ileum and colon. Agents with a low pill burden and favorable safety profile are more likely to enhance patient compliance in the long-term maintenance of UC remission. Two similarly designed multicenter, randomized, doubleblind, placebo-controlled, phase 3 trials (RCTs) have individually demonstrated significant efficacy of MG (1.5 g, q. d.) for the long-term maintenance of ulcerative colitis (UC). Additionally, an open-label extension trial (OLT) with new and rollover subjects from the two phase 3 trials was conducted to study the long term safety of MG for maintenance of UC remission. The integrated safety data in the expanded population of subjects who received MG from all three trials are presented here (All MG population). Methods: Data for the All MG analyses (n=557) included subjects who received MG in the two RCTs (n=367) and the OLT. The OLT included 197 MGtreated patients who rolled over from the RCTs; and 190 MG naive patients (83 placebo-treated patients from the RCTs, and 107 new patients) all in UC remission. Results: Of 557 patients included in the analysis, 250 patients were exposed for >1 year and 354 were exposed to MG (1.5 g, q.d.) for >6 months. Incidence of treatment-emergent adverse events (TEAEs) was 69.7% in the All MG group. Majority of TEAEs were mild or moderate in intensity, with a profile similar to that during the 6month RCTs. The notably lower incidence of UC flare observed in the RCTs for MG (10.9%) versus placebo (24.3%) was maintained (10.4%) in the OLT. Other common TEAEs in the All MG group were headache (13.8%), diarrhea (9.7%), nasopharyngitis (8.8%), abdominal pain (7.7%), sinusitis (5.4%), and nausea (5.2%). Incidences of serious adverse events and TEAEs leading to study discontinuation were comparable between the 6-month RCT group and the All MG population in the open label study. Occurrences of renal, hepatic, and pancreatic adverse events in patients in the open-label study were ≤1%. Long term compliance for the once-daily treatment regimen was high: mean compliance was ≥ 95% in each treatment group in the RCT population, and 88% for the All MG population. Conclusions: The favorable safety profile of MG when combined with a high compliance of once-daily dosing may support its dispensation as first-line therapy for long-term maintenance of UC remission.

T1200 Long-Term Safety of Once-Daily 1.5-G Mesalamine Granules in Patients in Remission from Ulcerative Colitis

Mesalamine granules (MG) are the first 5-aminosalicylate (5-ASA) formulation to use an innovative delivery system that combines delayedand extended-release mechanisms to release mesalamine directly in the ileum and colon. Agents with a low pill burden and favorable safety profile are more likely to enhance patient compliance in the long-term maintenance of UC remission. Two similarly designed multicenter, randomized, doubleblind, placebo-controlled, phase 3 trials (RCTs) have individually demonstrated significant efficacy of MG (1.5 g, q. d.) for the long-term maintenance of ulcerative colitis (UC). Additionally, an open-label extension trial (OLT) with new and rollover subjects from the two phase 3 trials was conducted to study the long term safety of MG for maintenance of UC remission. The integrated safety data in the expanded population of subjects who received MG from all three trials are presented here (All MG population). Methods: Data for the All MG analyses (n=557) included subjects who received MG in the two RCTs (n=367) and the OLT. The OLT included 197 MGtreated patients who rolled over from the RCTs; and 190 MG naive patients (83 placebo-treated patients from the RCTs, and 107 new patients) all in UC remission. Results: Of 557 patients included in the analysis, 250 patients were exposed for >1 year and 354 were exposed to MG (1.5 g, q.d.) for >6 months. Incidence of treatment-emergent adverse events (TEAEs) was 69.7% in the All MG group. Majority of TEAEs were mild or moderate in intensity, with a profile similar to that during the 6month RCTs. The notably lower incidence of UC flare observed in the RCTs for MG (10.9%) versus placebo (24.3%) was maintained (10.4%) in the OLT. Other common TEAEs in the All MG group were headache (13.8%), diarrhea (9.7%), nasopharyngitis (8.8%), abdominal pain (7.7%), sinusitis (5.4%), and nausea (5.2%). Incidences of serious adverse events and TEAEs leading to study discontinuation were comparable between the 6-month RCT group and the All MG population in the open label study. Occurrences of renal, hepatic, and pancreatic adverse events in patients in the open-label study were ≤1%. Long term compliance for the once-daily treatment regimen was high: mean compliance was ≥ 95% in each treatment group in the RCT population, and 88% for the All MG population. Conclusions: The favorable safety profile of MG when combined with a high compliance of once-daily dosing may support its dispensation as first-line therapy for long-term maintenance of UC remission.