Ulcerative Colitis: Safdi M

Sands BE, Sandborn WJ, Wolf DC, Katz S, Safdi M, Schwartz DA, Hanauer SB. · Gastrointestinal Unit and MGH Crohn's and Colitis Center, Massachusetts General Hospital, Boston, MA 02114, USA. · J Clin Gastroenterol. · Pubmed #16825929 No free full text.

Abstract: GOALS: Two uncontrolled, multicenter feasibility studies evaluated safety and pilot efficacy of selective granulocyte and monocyte adsorption apheresis (GMA) with the Adacolumn Apheresis System for treatment of moderate-to-severe ulcerative colitis (UC) and Crohn disease (CD) patients refractory/intolerant to conventional pharmacologic therapy. BACKGROUND: Patients with UC and CD, characterized by elevations in peripheral blood granulocytes, monocytes/macrophages, and proinflammatory mediators, may benefit from reductions in activated granulocytes and monocytes by selective apheresis. METHODS: Patients underwent weekly Adacolumn sessions for 5 weeks. Pilot efficacy assessments used disease activity index (DAI) for UC (0-12) or CD activity index (CDAI; 0-600) for CD. RESULTS: Eleven of 15 UC patients completed all 5 treatments. Mean DAI scores fell from 8.4+/-1.3 (baseline) to 5.2+/-2.9 (week 7). Five patients had DAI reductions of > or = 3 points at week 7. Fourteen of 15 CD patients completed all 5 treatments. Mean CDAI scores fell from 308.0+/-76.5 (baseline) to 200.6+/-117.4 (week 7). Nine CD patients responded (CDAI reductions > or = 70 points) at week 7. Remission (CDAI score < or = 150 at week 7) was observed in 6 patients. There were no device-related serious adverse effects. CONCLUSIONS: Treatment with Adacolumn may be feasible and effective in patients with moderate-to-severe refractory inflammatory bowel disease. Larger sham-controlled studies are ongoing.

Sandborn WJ, Sands BE, Wolf DC, Valentine JF, Safdi M, Katz S, Isaacs KL, Wruble LD, Katz J, Present DH, Loftus EV, Graeme-Cook F, Odenheimer DJ, Hanauer SB. · Mayo Clinic, Rochester, MN, USA. · Aliment Pharmacol Ther. · Pubmed #12786629 links to  free full text

Abstract: BACKGROUND: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. AIM: To evaluate repifermin for the treatment of active ulcerative colitis. METHODS: Eighty-eight patients with active ulcerative colitis were enrolled in a 6-week, double-blind trial. Patients were randomized to receive treatment for five consecutive days with intravenous repifermin at a dose of 1, 5, 10, 25 or 50 microg/kg, or placebo. The primary objective of the study was to evaluate the safety of repifermin. The primary efficacy outcome was clinical remission at week 4, defined as a score of zero on the endoscopic appearance and stool blood components of the Mayo score and a score of zero or unity on the stool frequency and physician's global assessment components. RESULTS: At week 4, the rates of clinical remission in the 1, 5, 10, 25 and 50 microg/kg repifermin groups were 19%, 9%, 0%, 0% and 0%, respectively, and 11% for the placebo group (P = 0.32 for repifermin vs. placebo). The frequencies of commonly occurring adverse events and severe adverse events were similar in both groups. CONCLUSIONS: Intravenous repifermin at a dose of 1-50 microg/kg was very well tolerated, but there was no evidence that repifermin was effective for the treatment of active ulcerative colitis at these doses. An additional study to determine the efficacy of repifermin at doses of > 50 microg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.

Pruitt R, Hanson J, Safdi M, Wruble L, Hardi R, Johanson J, Koval G, Riff D, Winston B, Cross A, Doty P, Johnson LK. · Vanderbilt University School of Medicine, Nashville Medical Research Institute, Nashville, Tennessee, USA. · Am J Gastroenterol. · Pubmed #12492193 No free full text.

Abstract: OBJECTIVE: Balsalazide is a novel azo-bonded 5-aminosalicylic acid treatment for mild-to-moderate ulcerative colitis. The study objective was to compare symptomatic remission rates with balsalazide and mesalamine while controlling for extent of disease and time since diagnosis in patients with active, mild-to-moderate ulcerative colitis. METHODS: A total of 173 patients with sigmoidoscopically verified ulcerative colitis were randomized to 8 wk of double-blind treatment with balsalazide 6.75 g/day or mesalamine 2.4 g/day. Both treatments provided 2.4 g/day of oral 5-aminosalicylic acid. Patients maintained symptom diaries throughout the treatment period. RESULTS: Overall, 46% of balsalazide- and 44% of mesalamine-treated patients achieved symptomatic remission. Higher response rates were noted in newly diagnosed patients with < or = 40 cm of disease (68% vs 61%) than in recently relapsed patients with >40 cm of disease (36% vs 25%). The median time to symptomatic remission was 12 days shorter with balsalazide (25 days) than with mesalamine (37 days). Significantly more balsalazide patients showed sigmoidoscopic (p = 0.002), stool frequency (p = 0.006), rectal bleeding (p = 0.006), and physician's global assessment score (p = 0.013) improvement by 14 days than did mesalamine patients. Similar proportions of patients reported adverse events (54% vs 64%), which were most commonly related to the gastrointestinal and central and peripheral nervous systems. CONCLUSIONS: Balsalazide is an effective and safe treatment for mild-to-moderate ulcerative colitis. Improvement of symptoms occurs considerably earlier with balsalazide than with mesalamine.

Hanauer SB, Sandborn WJ, Kornbluth A, Katz S, Safdi M, Woogen S, Regalli G, Yeh C, Smith-Hall N, Ajayi F. · Division of Gastroenterology, University of Chicago Medical Center, Chicago, Illinois 60637, USA. · Am J Gastroenterol. · Pubmed #16279903 No free full text.

Abstract: BACKGROUND AND AIMS: Preliminary data have shown that delayed release oral mesalamine (Asacol) dosed at 4.8 g/day provided additional efficacy benefit compared to 1.6 g/day in patients with mildly to moderately active ulcerative colitis. Additionally, Asacol dosed at 2.4 g/day has been proved to be more effective than 1.6 g/day. Whether 4.8 g/day of mesalamine (dosed with an investigational 800 mg tablet) is more effective than Asacol 2.4 g/day (dosed with a 400 mg tablet) in patients with moderately active ulcerative colitis is unknown. METHODS: A randomized, double-blind, controlled trial (ASCEND II) was conducted to evaluate the efficacy of 4.8 g/day of mesalamine in adults with active ulcerative colitis. Three hundred eighty-six patients with mild to moderate ulcerative colitis were randomized for treatment with mesalamine 2.4 g/day (400 mg tablet) or 4.8 g/day (800 mg tablet) for 6 wk. The primary efficacy population was 268 patients with moderately active ulcerative colitis treated with 2.4 g/day (n = 139) or 4.8 g/day (n = 129). The primary endpoint was the proportion of patients in each treatment group that achieved overall improvement ("treatment success," defined as either complete remission or a clinical response to therapy) from baseline at week 6. RESULTS: Seventy-two percent of patients receiving 4.8 g/day of mesalamine for moderate ulcerative colitis (89/124 patients) achieved treatment success at week 6, compared with 59% of those who received 2.4 g/day (77/130 patients) (p= 0.036). Both regimens were well tolerated. Adverse events and clinically significant changes in laboratory results were similar in both treatment groups. CONCLUSIONS: Patients with moderately active ulcerative colitis treated with 4.8 g/day of mesalamine (800 mg tablet) are significantly more likely to achieve overall improvement at 6 wk compared to patients treated with 2.4 g/day.