Bernd Bokemeyer

Publications of Bernd Bokemeyer

• FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease.

  Authors: Rayko Evstatiev, Philippe Marteau, Tariq Iqbal, Igor L Khalif, Jürgen Stein, Bernd Bokemeyer, Ivan V Chopey, Florian S Gutzwiller, Lise Riopel, Christoph Gasche

  Gastroenterology. 06/2011; 141(3):846-853.e1-2.

  Iron deficiency anemia (IDA) is common in chronic diseases and intravenous iron is an effective and recommended treatment. However, dose calculations and inconvenient administration may affectIron deficiency anemia (IDA) is common in chronic diseases and intravenous iron is an effective and recommended treatment. However, dose calculations and inconvenient administration may affect compliance and efficacy. We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen (FCM) with individually calculated iron sucrose (IS) doses in patients with inflammatory bowel disease (IBD) and IDA. This randomized, controlled, open-label, multicenter study included 485 patients with IDA (ferritin <100 μg/L, hemoglobin [Hb] 7-12 g/dL [female] or 7-13 g/dL [male]) and mild-to-moderate or quiescent IBD at 88 hospitals and clinics in 14 countries. Patients received either FCM in a maximum of 3 infusions of 1000 or 500 mg iron, or Ganzoni-calculated IS dosages in up to 11 infusions of 200 mg iron. Primary end point was Hb response (Hb increase ≥ 2 g/dL); secondary end points included anemia resolution and iron status normalization by week 12. The results of 240 FCM-treated and 235 IS-treated patients were analyzed. More patients with FCM than IS achieved Hb response (150 [65.8%] vs 118 [53.6%]; 12.2% difference, P = .004) or Hb normalization (166 [72.8%] vs 136 [61.8%]; 11.0% difference, P = .015). Both treatments improved quality of life scores by week 12. Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience. Deviations from scheduled total iron dosages were more frequent in the IS group. The simpler FCM-based dosing regimen showed better efficacy and compliance, as well as a good safety profile, compared with the Ganzoni-calculated IS dose regimen.

• A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease.

  Authors: Iris Dotan, Daniel Rachmilewitz, Stefan Schreiber, Rami Eliakim, C Janneke van der Woude, Asher Kornbluth, Alan L Buchman, Shimon Bar-Meir, Bernd Bokemeyer, Eran Goldin, Christian Maaser, Uma Mahadevan, Ursula Seidler, Jörg C Hoffman, Douglas Homoky, Terry Plasse, Barbara Powers, Paul Rutgeerts, Daniel Hommes

  Gut. 06/2010; 59(6):760-6.

  Semapimod, a small molecule known to inhibit proinflammatory cytokine activity, was studied to determine the optimal dose necessary to achieve a response in patients with moderate to severe Crohn'sSemapimod, a small molecule known to inhibit proinflammatory cytokine activity, was studied to determine the optimal dose necessary to achieve a response in patients with moderate to severe Crohn's disease (CD). A randomised, double-blind, placebo-controlled trial (CD04) was carried out followed by an open-label extension study (CD05). The trial was conducted in international multicentre outpatient clinics and included patients with moderate to severe CD (Crohn's Disease Activity Index (CDAI) 250-400). Placebo was administered for 3 days; 60 mg semapimod intravenously for 1 day with placebo for 2 days; or 60 mg semapimod intravenously for 3 days. Participants who completed CD04 could participate in the open-label extension study, CD05, to receive up to five additional semapimod HCl 60 mg daily doses three times every 6-8 weeks. The main outcome measures were CDAI, Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Endoscopic Inflammation Score (CDEIS) and serum C-reactive protein (CRP) concentration. 152 patients were randomised in CD04. Responses for 1 and 3 day regimens were similar to placebo for CDAI (p=0.82), IBDQ (p=0.85), CDEIS (p=0.57) and CRP (p=0.40). The only noteworthy treatment-related safety finding was infusion reaction (phlebitis): 7.3, 34.8 and 62.7% for the placebo and 1 and 3 day semapimod treatment groups, respectively (p<0.001). In the open-label CD05 study (included=119 patients) a posthoc analysis showed that the mean CDAI improved in patients receiving 6 compared with < or = 3 cumulative doses (204.1+/-83 vs 251.4+/-103.05, p=0.006). Single and 3 day dosing of semapimod (< or = 180 mg) was ineffective for the treatment of moderate to severe CD. However, cumulative dosing > or = 360 mg was associated with decreased CDAI in a limited number of patients.

• Mesalamine once daily is more effective than twice daily in patients with quiescent ulcerative colitis.

  Authors: Axel U Dignass, Bernd Bokemeyer, Henning Ad Amek, Michael Mross, Lars Vinter-Jensen, Norbert Börner, Jouni Silvennoinen, Gie Tan, Marco Oudkerk Pool, Theo Stijnen, Peter Dietel, Tobias Klugmann, Severine Vermeire, Aomesh Bhatt, Henri Veerman

  Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 04/2009;

  BACKGROUND & AIMS:: Oral mesalamine (5-aminosalicylate) is the current standard of care for mild-to-moderate ulcerative colitis (UC). We investigated the efficacy and safety of once-dailyBACKGROUND & AIMS:: Oral mesalamine (5-aminosalicylate) is the current standard of care for mild-to-moderate ulcerative colitis (UC). We investigated the efficacy and safety of once-daily administration of prolonged-release mesalamine granules in maintenance of remission in patients with quiescent UC, compared with the well-established twice-daily dosing regimen. METHODS:: In this multicenter, randomized, single-blind, non-inferiority trial, 362 patients with quiescent UC were randomly assigned (1:1) to groups that were given oral mesalamine, 2 g, once daily or 1 g twice-daily for 12 months. The primary objective was to compare remission rates at 1 year, based on the UC disease activity index score, using Kaplan-Meier methodology. RESULTS:: At 1 year, 70.9% of the group given 2 g mesalamine once daily remained in remission vs 58.9% of the group given 1 g mesalamine twice daily; this difference was statistically significant ( P =.024), indicating the increased efficacy of once daily, compared with twice daily, dosing. Self-reported adherence to therapy, measured by visual analog scale score after 4, 8 and 12 months, was significantly greater in the group given 2 g mesalamine once daily, compared with twice daily, at all but 1 study visit ( P<.05). Compliance measured by medication taken was not significantly different between the groups. The difference between the 2 groups in overall incidence of adverse events was not statistically significant ( P =.23). CONCLUSIONS:: Patients with UC given prolonged-release oral mesalamine 2 g once daily had better remission rates, acceptability, and self-reported adherence to therapy compared with patients given oral mesalamine 1 g twice daily.

• A systematic survey evaluating 6-thioguanine-related hepatotoxicity in patients with inflammatory bowel disease.

  Authors: Alexander Teml, Matthias Schwab, Daan W Hommes, Sven Almer, Milan Lukas, Thomas Feichtenschlager, Timothy Florin, Julia Seiderer, Wolfgang Petritsch, Bernd Bokemeyer, Wolfgang Kreisel, Klaus R Herrlinger, Peter Knoflach, Bruno Bonaz, Thomas Klugmann, Hans Herfarth, Nikolaus Pedarnig, Walter Reinisch

  Wiener klinische Wochenschrift. 01/2007; 119(17-18):519-26.

  OBJECTIVE: Drug-induced liver injury was recently reported as a major complication leading to hepatic nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease (IBD) andOBJECTIVE: Drug-induced liver injury was recently reported as a major complication leading to hepatic nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease (IBD) and 6-thioguanine (6-TG) therapy. The aim of the study was to evaluate the prevalence of 6-TG-related hepatotoxicity in a large multi-centered IBD population by means of a systematic online survey. METHODS: Clinical and laboratory data, imaging techniques (sonography, CT, MRI) and histology of liver biopsies were surveyed in IBD patients treated with 6-TG. The decision on whether liver imaging and/or liver biopsy were performed was exclusively at the discretion of the investigator. RESULTS: 6-TG use was fully documented in 296 patients (median treatment duration 56 weeks, range < 1-207). Laboratory signs of drug-induced liver injury were found in 43 patients (14.5%). Liver imaging revealed pathologic results in 68/176 patients (38.6%). Liver biopsy was performed in a subset of 60 patients; using silver-reticulin staining (n = 59), NRH was considered in 16 patients (27.1%). Age was the only independent, albeit weak, risk factor for development of NRH. CONCLUSION: This large online survey confirms the strong association between 6-TG treatment and the significant risk of development of NRH in patients with IBD. The definitive diagnosis of NRH depends solely upon liver biopsy.

• Randomized, double blind controlled trial of subcutaneous recombinant human interleukin-11 versus prednisolone in active Crohn's disease.

  Authors: Klaus R Herrlinger, Thomas Witthoeft, Andreas Raedler, Bernd Bokemeyer, Thomas Krummenerl, Jorg-Dieter Schulzke, Norbert Boerner, Bruno Kueppers, Joerg Emmrich, Axel Mescheder, Ulrich Schwertschlag, Mark Shapiro, Eduard F Stange

  The American journal of gastroenterology. 04/2006; 101(4):793-7.

  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 ofBACKGROUND: 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 Crohn's 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 (deltaCDAI > 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.

• Mesalamine Once Daily Is More Effective Than Twice Daily in Patients With Quiescent Ulcerative Colitis

  Authors: Axel U. Dignass, Bernd Bokemeyer, Henning Adamek, Michael Mross, Lars Vinter-Jensen, Norbert Börner, Jouni Silvennoinen, Gie Tan, Marco Oudkerk Pool, Theo Stijnen, Peter Dietel, Tobias Klugmann, Severine Vermeire, Aomesh Bhatt, Henri Veerman

  Clinical Gastroenterology and Hepatology.

  Background & AimsOral mesalamine (5-aminosalicylate) is the current standard of care for mild-to-moderate ulcerative colitis. We investigated the efficacy and safety of once daily administration ofBackground & AimsOral mesalamine (5-aminosalicylate) is the current standard of care for mild-to-moderate ulcerative colitis. We investigated the efficacy and safety of once daily administration of prolonged-release mesalamine granules in maintenance of remission in patients with quiescent ulcerative colitis, compared with the well established twice daily dosing regimen.MethodsIn this multicenter, randomized, single blind, noninferiority trial, 362 patients with quiescent ulcerative colitis were randomly assigned (1:1) to groups that were given oral mesalamine 2 g, once daily, or 1 g, twice daily, for 12 months. The primary objective was to compare remission rates at 1 year, based on the ulcerative colitis disease activity index score, using Kaplan–Meier methodology.ResultsAt 1 year, 70.9% of the group given 2 g mesalamine once daily remained in remission vs 58.9% of the group given 1 g mesalamine twice daily; this difference was statistically significant (P = .024), indicating the increased efficacy of once daily, compared with twice daily, dosing. Self-reported adherence to therapy, measured by visual analog scale score after 4, 8, and 12 months, was significantly greater in the group given 2 g mesalamine once daily, compared with twice daily, at all but 1 study visit (P < .05). Compliance measured by medication taken was not significantly different between the groups. The difference between the 2 groups in overall incidence of adverse events was not statistically significant (P = .23).ConclusionsPatients with ulcerative colitis given prolonged-release oral mesalamine 2 g once daily had better remission rates, acceptability, and self-reported adherence to therapy compared with patients given oral mesalamine 1 g twice daily.