Ralph Mueller

Publications of Ralph Mueller

• 3g mesalazine granules are superior to 9mg budesonide for achieving remission in active ulcerative colitis: a double-blind, double-dummy, randomised trial.

  Authors: Volker Gross, Ivan Bunganic, Elena A Belousova, Tatyana L Mikhailova, Limas Kupcinskas, Gediminas Kiudelis, Zsolt Tulassay, Libor Gabalec, Andrey E Dorofeyev, Jelena Derova, Karin Dilger, Roland Greinwald, Ralph Mueller

  Journal of Crohn's & colitis. 04/2011; 5(2):129-38.

  Budesonide may be an effective therapy for mild-to-moderately active ulcerative colitis (UC). This study aimed to demonstrate non-inferiority for oral 9mg budesonide once daily (OD) versus 3gBudesonide may be an effective therapy for mild-to-moderately active ulcerative colitis (UC). This study aimed to demonstrate non-inferiority for oral 9mg budesonide once daily (OD) versus 3g mesalazine granules OD. This was an eight-week randomised, double-blind, double-dummy, multicentre study in which patients with mild-to-moderately active UC, defined as Clinical Activity Index (CAI) ≥6 and Endoscopic Index (EI) ≥4, received budesonide (Budenofalk® 3mg capsules×3) or mesalazine (Salofalk® 1000mg granules×3). The primary endpoint was clinical remission at week 8 (CAI ≤4 with stool frequency and rectal bleeding subscores of "0"). 343 patients were randomised (177 budesonide, 166 mesalazine). Fewer patients achieved the primary endpoint with budesonide versus mesalazine (70/177 [39.5%] versus 91/166 [54.8%]) with a difference in proportions of -15.3% (95% CI [-25.7%, -4.8%]; p=0.520 for non-inferiority). The median time to first resolution of symptoms was 14.0 days (budesonide) and 11.0 days (mesalazine) (hazard ratio 1.19; 95% CI [0.94, 1.51]). Mucosal healing was observed in 54/177 (30.5%) budesonide patients versus 65/166 (39.2%) mesalazine patients, a difference of -8.6% (95% CI [-18.7%, 1.4%]; p=0.093). The incidences of adverse events (budesonide 26.6%, mesalazine 25.3%) and serious adverse events (budesonide 1.7%, mesalazine 1.2%) were similar. Once-daily 3g mesalazine administered as granules is superior to 9mg budesonide OD administered as capsules for achieving remission in mild-to-moderately active UC. However, it is noteworthy that remission of UC was attained in about 40% of budesonide-treated patients with a rapid onset of resolution.

• Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial.

  Authors: Walter Reinisch, Sieglinde Angelberger, Wolfgang Petritsch, Olga Shonova, Milan Lukas, Simon Bar-Meir, Alexander Teml, Elke Schaeffeler, Matthias Schwab, Karin Dilger, Roland Greinwald, Ralph Mueller, Eduard F Stange, Klaus R Herrlinger

  Gut. 06/2010; 59(6):752-9.

  The aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn's disease (CD) with moderate or severeThe aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn's disease (CD) with moderate or severe endoscopic recurrence. This was a 1 year, double-blind, double-dummy, randomised study which took place in 21 gastroenterology centres in Austria, the Czech Republic, Germany and Israel. The study participants were 78 adults with CD who had undergone resection with ileocolonic anastomosis in the preceding 6-24 months without subsequent clinical recurrence and with a Crohn's disease activity index (CDAI) score <200, but with moderate or severe endoscopic recurrence. The study drugs were azathioprine 2.0-2.5 mg/kg/day or mesalazine 4 g/day over 1 year. The primary end point was therapeutic failure during 1 year, defined as a CDAI score > or = 200 and an increase of > or = 60 points from baseline, or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction. Treatment failure occurred in 22.0% (9/41) of azathioprine-treated patients and 10.8% (4/37) of mesalazine-treated patients, a difference of 11.1% (95% CI -5.0% to 27.3%, p=0.19). Clinical recurrence was significantly less frequent with azathioprine versus mesalazine (0/41 (0%) vs 4/37 (10.8%), p=0.031), whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprine-treated patients (9/41 (22.0%) vs 0%, p=0.002). The proportion of patients showing > or = 1 point reduction in Rutgeerts score between baseline and month 12 was 63.3% (19/30) and 34.4% (11/32) in the azathioprine and mesalazine groups, respectively (p=0.023). In this population of patients with postoperative CD at high risk of clinical recurrence, superiority for azathioprine versus mesalazine could not be demonstrated for therapeutic failure.

• A randomized double-blind placebo-controlled study showing that budesonide is effective in treating lymphocytic colitis.

  Authors: Stephan Miehlke, Ahmed Madisch, Diana Karimi, Susann Wonschik, Eberhard Kuhlisch, Renate Beckmann, Andrea Morgner, Ralph Mueller, Roland Greinwald, Gerhard Seitz, Gustavo Baretton, Manfred Stolte

  Gastroenterology. 04/2009;

  BACKGROUND AND AIMS:: Budesonide is effective in treating collagenous colitis, but there is no established treatment for lymphocytic colitis. We performed a randomized, double-blind,BACKGROUND AND AIMS:: Budesonide is effective in treating collagenous colitis, but there is no established treatment for lymphocytic colitis. We performed a randomized, double-blind, placebo-controlled study to evaluate the effects of budesonide in patients with lymphocytic colitis. METHODS:: 42 patients (median age 61 years) with lymphocytic colitis and chronic diarrhea were randomly assigned to groups that were given oral doses of budesonide (9 mg/day) or placebo for 6 weeks. Non-responders at Week 6 were given open-label budesonide (9 mg/day) for 6 additional weeks. A complete colonoscopy and histological and quality of life analyses were performed at baseline and at Week 6. The primary endpoint was clinical remission at 6 weeks, with last observation carried forward (LOCF). All patients that left the study in clinical remission were followed for relapse. RESULTS:: At Week 6, 86% of patients given budesonide were in clinical remission (with LOCF) compared with 48% of patients given placebo ( P = 0.010). Furthermore, open-label budesonide therapy induced clinical remission in 7 of 8 patients given placebo. Histological remission was observed in 73% of patients given budesonide compared with 31% given placebo ( P = 0.030). Only 1 patient discontinued budesonide therapy prematurely. During a mean follow-up period of 14 months, 15 patients (44.1%) experienced a clinical relapse (after a mean of 2 months); 8 of the relapsing patients were re-treated with and responded again to budesonide. CONCLUSIONS:: Budesonide effectively induces clinical remission in patients with lymphocytic colitis and significantly improves histology results after 6 weeks. Clinical relapses occur but can be treated again with budesonide.