Thomas Witthoeft

Response of refractory colitis to intravenous or oral tacrolimus (FK506)

Intravenous cyclosporine has proven to be an alternative to emergency colectomy in steroid-refractory ulcerative colitis, whereas the experience with FK506 is limited. In this report we compare intravenous to oral FK506 treatment in 38 patients with refractory ulcerative (n = 33) or indeterminate (n = 5) colitis. FK506 was started intravenously in the first group (n = 18) at a dose of 0.01 to 0.02 mg/kg up to 14 days, followed by 0.1 to 0.2 mg/kg orally, or was started orally at this dose in a second group (n = 20). Additional azathioprine/6-mercaptopurine was given and steroids were tapered in responding patients, followed by a dose reduction of FK506. Clinical disease activity and laboratory parameters were assessed to evaluate efficacy and safety. Primary objectives were the induction of remission (Truelove index of mild) and colectomy-free survival. Treatment lasted for a mean of 7.6 months, and the mean observation period was 16.2 months. Eighteen of 38 patients improved within 14 days, and a complete remission was achieved in 13 patients after 1 month. A colectomy within 1 month was performed in 3 of 38 patients. The overall colectomy rate was 34%. One-half of the patients with a minimum follow-up of 2 years required a colectomy. Intravenous and per oral administration were equally safe and effective. The most frequent adverse events included tremor, hyperglycemia, hypertension, and infection, but none were severe. Renal impairment was rare and subsided upon drug withdrawal. In conclusion, FK506 is effective in the treatment of refractory colitis with per oral dosing being equivalent to intravenous administration.

Randomized, Double Blind Controlled Trial of Subcutaneous Recombinant Human Interleukin-11 Versus Prednisolone in Active Crohn's Disease

BACKGROUND: Interleukin-11 has shown benefit in animal inflammatory bowel disease models. Recently, recombinant human interleukin-11 (rhIL-11) has been observed to induce remission in a subset of patients with mild to moderate Crohns disease (CD). The present study compared the efficacy of rhIL-11 versus prednisolone in remission induction in CD.METHODS: Patients with active CD were randomly assigned to receive either subcutaneous rhIL-11 (1 mg once weekly) and prednisolone placebo tablets, or active prednisolone (60 mg/day) and rhIL-11 placebo, for 12 weeks. Prednisolone/placebo was tapered after week 1, and patients were assessed every second week.RESULTS: Fifty-one patients received medication: 13/27 (rhIL-11) and 17/24 (prednisolone) completed 12 weeks of treatment. Remission rates (intent to treat) for rhIL-11 versus prednisolone were 4%versus 46% at week 4 (p < 0.001) and 19%versus 50% at week 6 (p < 0.05). Response to treatment (ΔCDAI > 100) was seen in 19% (rhIL-11) versus 63% (prednisolone) after 4 weeks (p < 0.002) and 37%versus 63% after 6 weeks (p= 0.1). After 12 weeks of treatment, it was observed that 22% (rhIL-11) versus 21% (prednisolone) had remained in remission. Frequent side effects of rhIL-11 included fever (n = 3), rash (4), arthralgia/arthritis (3), nausea/vomiting (3), and headache (6).CONCLUSION: rhIL-11 is well tolerated but significantly inferior when compared to prednisolone in short-term remission induction in patients with active CD. In this patient cohort, both treatments appeared to be poor in maintaining remission over a period of 3 months.

Su1072 Treatment of Chronic Hepatitis C Genotype 1 (G1) Infection With Boceprevir (Victrelis®) in German Real-Life: Impact of Hemoglobin Decline on Virologic Response

Treatment of Chronic Hepatitis C Genotype 1 (G1) Infection With Boceprevir (Victrelis®) in German Real-Life: Impact of Hemoglobin Decline on Virologic Response Gerlinde Teuber, Peter Buggisch, Hanns Lohr, Hermann Steffens, Michael Kraus, Christine John, Peter Geyer, Bernd Weber, Thomas Witthoeft, Andreas Herrmann, Mark Hoesl, Uwe Naumann, Tarek Dahhan, Dagmar Hartmann, Bernd Dreher, Manfred Bilzer

W1001 The Role of Cholesterol On Sustained Virological Response (SVR) in the Treatment of Genotype-1 Infected Hepatitis C (cHC) Patients with Peginterferon Alfa-2a (PEG) and Ribavirin (RBV)

S. Mauss1, E. Zehnter2, D. Hueppe3, K. Kaiser4, K. Boeker5, T. Lutz6, R. Heyne7, C. John9, G. Moog9, A. Schober10, R. Pfaff11, A. Zipf12, S. Racky13, J. Lohmeyer14, B. Bokemeyer15, B. Kallinowski16, T. Witthoeft17, U. Alshuth18. 1Center For HIV and Hepatogastrenterology, Duesseldorf, 2Center of Gastroenterology, Dortmund, 3Center of Gastroenterology, Herne, 4Klinikum der Eberhard-Karls-Universitat, Tuebingen, 5Center of Gastroenterology, Hannover, 6 Infektiologikum, Frankfurt, 7Center of Gastroenterology and Livercenter, Berlin, 8Center of Gastroenterology, Berlin, 9Center of Gastroenterology, Kassel, 10Center of Gastroenterology, Goettingen, 11Center of Gastroenterology, Giessen, 12Center of Gastroenterology, Mannheim, 13Center of Gastroenterology, Bad Schwalbach, 14Justus Liebig-Universitat Giessen, Giessen, 15Gastroenterology Practice, Minden, 16Center of Gastroenterology, Schwetzingen, 17Medical Department I, Div. of Gastroenterology, University Hospital Schleswig-Holstein Campus, Luebeck, 18Roche Pharma AG, Grenzach-Wyhlen, Germany E-mail: stefan.mauss@center-duesseldorf.de