Ulcerative Colitis: Schreiber S

Schreiber S, Anonymous00193. · No affiliation provided · Z Gastroenterol. · Pubmed #11215370 No free full text.

This publication has no abstract.

Schreiber S, Kamm MA, Lichtenstein GR. · Medicine & Gastroenterology, Institute for Clinical Molecular Biology, Center for Conservative Medicine, Schittenhelmstr. 12, 24105, Kiel, Germany. · Expert Rev Gastroenterol Hepatol. · Pubmed #19072380 No free full text.

Abstract: Mesalamine with MMX Multi Matrix System technology (hereafter referred to as MMX mesalamine) is an oral, high-strength (1.2 g/tablet), once-daily formulation of 5-aminosalicylic acid used for the treatment of ulcerative colitis. This new formulation has been designed to provide delayed and prolonged 5-aminosalicylic acid release throughout the colon. In recent clinical studies, MMX mesalamine (taken as a once-daily dose of 2.4 or 4.8 g) effectively induced clinical remission and mucosal healing versus placebo in patients with active, mild-to-moderate ulcerative colitis. Once remission was achieved, MMX mesalamine effectively maintained disease remission in the majority of patients for at least 12 months. In this paper, we comprehensively review the results of studies exploring the clinical pharmacology, efficacy and safety of MMX mesalamine in patients with ulcerative colitis, and examine the implications of these findings on clinical practice.

Nikolaus S, Schreiber S. · Klinik für Allgemeine Innere Medizin, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Schittenhelm Strasse 12, 24105, Kiel, Germany. · Internist (Berl). · Pubmed #18584139 No free full text.

Abstract: The utility of infliximab as a therapy for complicated inflammatory bowel disease (Crohn's disease, ulcerative colitis) has been established through large prospective trials in the last decade. With approval of adalimumab physicians and patients now have the choice between two different anti-TNF agents. In addition to control of inflammation, the avoidance of chronic exposure to glucocorticoids has become a primary reason to use anti-TNF therapy. Early use of anti-TNF therapy in the course of disease is a potential new indication. The increasingly critical appreciation of side effects promotes mono-therapy with anti-TNF agents.

Panaccione R, Rutgeerts P, Sandborn WJ, Feagan B, Schreiber S, Ghosh S. · Department of Medicine, University of Calgary, Calgary, AB, Canada. · Aliment Pharmacol Ther. · Pubmed #18532990 No free full text.

Abstract: BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the intestine, which frequently require surgery for complications or failure of medical therapy. AIM: To seek evidence and provide direction for clinicians on optimal strategies to enable steroid free remission in inflammatory bowel disease. METHODS: Scientific literature was reviewed using MEDLINIE with a specific focus on medical therapies for inducing and maintaining remission of CD and UC. The results were discussed at a roundtable meeting to reach a consensus on key issues. RESULTS: Several therapies have demonstrated efficacy for the treatment of active, moderate-to-severe CD and UC. These include agents, which induce remission [corticosteroids, infliximab and adalimumab (CD only)] or maintain remission and spare corticosteroids [azathioprine, mercaptopurine, methotrexate (CD only), infliximab and adalimumab (CD only)]. Wide variability exists in the use of these agents. CONCLUSION: Treatment strategy algorithms are developed for use of these therapies that maximize remission and minimize corticosteroid dependence in patients with moderate-to-severe CD and UC.

Nikolaus S, Schreiber S. · Department of General Internal Medicine, Christian-Albrechts-University, Kiel, Germany. · Gastroenterology. · Pubmed #17983810 No free full text.

Abstract: The diagnosis of inflammatory bowel disease (IBD) with its 2 main subforms, Crohn's disease and ulcerative colitis, is based on clinical, endoscopic, radiologic, and histologic criteria. This paradigm remains unchanged despite the advent of new molecular technologies for the examination of serum proteins and genetic sequences, respectively. The main innovations in diagnostic technologies include the development of more sophisticated endoscopic and noninvasive imaging techniques with the aim of improving the identification of complications, in particular malignant diseases associated with IBD. The future will see further progress in the identification of genetic susceptibility factors and of protein biomarkers and their use to describe the molecular epidemiology of IBD. It can be expected that future diagnostic algorithms will include molecular parameters to detect early disease or guide therapies by predicting the individual course of disease.

Mascheretti S, Schreiber S. · Institute for Clinical Molecular Biology, Kiel, Germany. · Am J Pharmacogenomics. · Pubmed #16078858 No free full text.

Abstract: Inflammatory bowel disease (IBD), with its two subforms of Crohn disease and ulcerative colitis, is a polygenic disease that manifests due to environmental trigger factors on the background of a complex genetic predisposition. The first risk gene underlying susceptibility to Crohn disease has been identified as CARD15 (located on chromosome 16q12, encoding NOD2). Three single nucleotide polymorphisms in the leucine rich region (LRR) of this gene are strongly and independently associated with Crohn disease susceptibility and explain up to 20% of the total genetic predisposition for Crohn disease. These variants have been consistently replicated as associated with a particular sub-phenotype characterized by small bowel (ileum) involvement and early age at onset. Presently, genetic testing for the CARD15 variants has only a modest relevance in clinical practice.The most attractive use of genetic testing is for the prediction of response to therapy. Most therapies only show efficacy in subgroups of patients and no clinical parameters are available to distinguish, prior to therapy, whether the patients will be responders or non-responders, or if the patients will experience adverse effects. The pharmacogenetic basis of toxicity is well known for azathioprine: several thiopurine methyltransferase (TPMT) polymorphisms that are associated with reduced activity of this thiopurine drug metabolizing enzyme result in cytotoxic and immunosuppressive adverse effects of azathioprine. Genetic screening, which has found its way into routine clinical diagnostics, allows the identification of the patients who will not tolerate a standard dose of the drug. The extensive search for genetic predictors of response to the anti-tumor necrosis factor treatment with infliximab, which results in a remission rate of 30-40%, has, however, failed to identify a variation associated with a differential response.

Hoffmann JC, Zeitz M, Bischoff SC, Brambs HJ, Bruch HP, Buhr HJ, Dignass A, Fischer I, Fleig W, Fölsch UR, Herrlinger K, Höhne W, Jantschek G, Kaltz B, Keller KM, Knebel U, Kroesen AJ, Kruis W, Matthes H, Moser G, Mundt S, Pox C, Reinshagen M, Reissmann A, Riemann J, Rogler G, Schmiegel W, Schölmerich J, Schreiber S, Schwandner O, Selbmann HK, Stange EF, Utzig M, Wittekind C. · Medizinische Klinik I mit Schwerpunkt Gastroenterologie/Infektiologie/Rheumatologie, Charité, Universitätsmedizin Berlin. · Z Gastroenterol. · Pubmed #15455267 No free full text.

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Mascheretti S, Croucher PJ, Schreiber S. · 1st Department of Medicine, Christian-Albrechts-Universtität Kiel, Schittenhelmstr. 12, Kiel D-24105, Germany. · Best Pract Res Clin Gastroenterol. · Pubmed #15157830 No free full text.

Abstract: The therapeutic efficacy and toxicity of many commonly employed drugs show interindividual variations that relate to several factors, including genetic variability in drug-metabolizing enzymes, transporters or targets. The study of the genetic determinants influencing interindividual variations in drug response is known as pharmacogenetics. The ability to identify, through preliminary genetic screening, the patients most likely to respond positively to a medication should facilitate the best choice of treatment for each patient; drugs likely to exhibit low efficacy or to give negative side-effects can be avoided. Among the medications used for inflammatory bowel disease, the best studied pharmacogenetically is azathioprine. The hematopoietic toxicity of azathioprine is due to single nucleotide polymorphisms in the thiopurine S-methyltransferase enzyme. Additionally, likely gene targets have been investigated to predict the response to glucocorticoids and infliximab, a monoclonal antibody against tumour necrosis factor that induces remission in approximately 30-40% of patients. However, no genetic predictor of response has been identified in either case.

Kühbacher T, Schreiber S, Fölsch UR. · I. Medizinische Klinik, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Schittenhelmstrasse 12, 24105 Kiel, Germany. · Langenbecks Arch Surg. · Pubmed #15133672 No free full text.

Abstract: Ulcerative colitis is characterized by chronic inflammation of the colon. Typical symptoms are diarrhoea, rectal bleeding, abdominal pain and fever. The aetiology of the disease is unclear. The inflammation can be localized in the rectum or can extend to the left side or the whole colon. Treatment for induction and remission maintenance depends on the severity and extension of mucosal inflammation. Topical 5-aminosalicylates have been shown in studies to be the treatment of choice in mild to moderate ulcerative colitis. Oral 5-aminosalicylates can be used in distal, mild and moderate ulcerative colitis and for remission maintenance. For patients with a more extended or severe inflammation, oral or i.v. corticosteroids should be used. Patients with severe and/or chronic disease require immunosuppressive therapy with azathioprine or 6-mercaptopurine. For patients with severe, chronic, refractory disease, cyclosporine i.v. can be used. If no response to treatment is seen, proctocolectomy should be considered. Biological agents such as beta-Interferon seem to be effective in mild to moderately ulcerative colitis, but further studies have to be performed.

Fölsch UR, Hoffmann J, Höhne W, Janke KH, Klump B, Rogler G, Schreiber S. · Klinik für Allgemeine Innere Medizin, I. Medizinische Klinik, Universitätsklinikum Kiel, Schittenhelmstrasse 12, 24105 Kiel. · Internist (Berl). · Pubmed #12524923 No free full text.

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Schreiber S, Hampe J, Grebe J, Nikolaus S, Stoll M, Fölsch UR. · Klinik für Allgemeine Innere Medizin, Christian-Albrechts-Universität zu Kiel, Schittenhelmstrasse 12, 24105 Kiel. · Internist (Berl). · Pubmed #12524914 No free full text.

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Kroesen AJ, Schreiber S, Buhr HJ. · Chirurgische Klinik und Poliklinik I, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany. · Zentralbl Chir. · Pubmed #12476363 No free full text.

Abstract: Ulcerative colitis can be cured with a reasonable quality of life by the complete excision of the colorectum and construction of an ileoanal pouch. The cure is incomplete since there is a certain incidence of a so called pouchitis. Pouchitis occurs with a frequency of 36 %. A single episode of a pouchitis can be cured easily, but in 8-32 % the concerned patients develop a chronic pouchitis. There are many signs that pouchitis might be a remanifestation of ulcerative colitis. This article gives an overview on the actual state of pathophysiology, pathogenesis and therapy of this disease. Apart of that the surgical aspects of the disease are described.

Mickisch O, Baniewicz W, Lutz-Vorderbrügge A, Schreiber S, Küppers B. · Gastroenterologische Schwerpunktpraxis, Mannheim, Germany. · Z Gastroenterol. · Pubmed #11961733 No free full text.

Abstract: The development of a stepwise therapy, as detailed below, can be administered to the mostly young patients with Crohn's disease and ulcerative colitis on an out-patient basis and appropriate to their needs. This is true not only for the activity of the disease, but also for extraintestinal manifestations. The numerous variations in the stepwise anti-inflammatory therapy of chronic inflammatory bowel disease, but also in the substitution therapy of deficiency states and the therapy of accompanying extraintestinal diseases provide the gastroenterologist with the possibility of a long-term treatment tailored to the needs of the individual patient.

Stange EF, Riemann J, von Herbay A, Lochs H, Fleig WE, Schölmerich J, Kruis W, Porschen R, Bruch HP, Zeitz M, Schreiber S, Moser G, Matthes H, Selbmann HK, Goebell H, Caspary WF. · Abteilung Innere Medizin 1 Robert-Bosch-Krankenhaus Auerbachstrasse 110 70376 Stuttgart. · Z Gastroenterol. · Pubmed #11215358 No free full text.

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Pena-Rossi C, Schreiber S, Golubovic G, Mertz-Nielsen A, Panes J, Rachmilewitz D, Shieh MJ, Simanenkov VI, Stanton D, Graffner H. · New Therapies, Merck Serono International S.A., Geneva, Switzerland. · Aliment Pharmacol Ther. · Pubmed #19145731 No free full text.

Abstract: BACKGROUND: Ulcerative colitis (UC) pathophysiology is characterized by an imbalance between pro- and anti-inflammatory cytokines. Interferon (IFN)-beta-1a has potent immunoregulatory properties, including stimulation of host defence mechanisms and thus represents a potential treatment. AIM: To extend pilot data and identify a suitable dose of IFN-beta-1a to achieve endoscopically confirmed remission (ECR) in patients with moderately active UC and to evaluate safety. METHODS: In this multicentre, double-blind, placebo-controlled trial, adults with moderately active UC were randomized to IFN-beta-1a 44 or 66 microg, or placebo, subcutaneously three times weekly for 8 weeks, with a 4-week follow-up. RESULTS: Endoscopically-confirmed remission was observed in 23.4% [95% confidence interval (CI): 13.8-35.7] of placebo patients, 29.2% (95% CI: 18.6-41.8) of the IFN-beta-la 44 microg group and 20.0% (950% CI: 11.1-31.8) of the 66 microg group (P = 0.45). Improvements with IFN-beta-1a 44 microg were greater than with placebo for most secondary efficacy outcomes, although significance was not achieved. Placebo response rates were higher than expected from previous trials. Adverse events were similar to the known safety profile of IFN treatment. CONCLUSIONS: Interferon-beta-1a was generally well tolerated at the doses tested, but a significant therapeutic benefit in patients with UC was not observed.

Kamm MA, Lichtenstein GR, Sandborn WJ, Schreiber S, Lees K, Barrett K, Joseph R. · St Vincent's Hospital, Department of Medicine, University of Melbourne, Melbourne, Australia. · Inflamm Bowel Dis. · Pubmed #18671232 No free full text.

Abstract: BACKGROUND: Many patients with ulcerative colitis (UC) respond to mesalamine therapy within 8 weeks. Those not achieving remission after 8 weeks are often treated with steroids or other immunosuppressive therapies. This study aimed to determine the effect of 8 weeks' high-dose MMX mesalamine extension therapy in patients with active, mild-to-moderate UC who had previously failed to achieve complete remission in 2 phase III, double-blind, placebo-controlled studies of MMX mesalamine (SPD476-301 and -302). METHODS: Patients with active, mild-to-moderate UC who did not achieve clinical and endoscopic remission after <or=8 weeks' treatment with MMX mesalamine (2.4 or 4.8 g/day), ASACOL (mesalamine) delayed-release tablets 2.4 g/day, or placebo in the phase III studies received MMX mesalamine 4.8 g/day for 8 weeks. The aim was to assess remission at week 8, defined as a total modified UC Disease Activity Index score of <or=1, calculated as: scores of 0 for rectal bleeding and stool frequency, a combined Physician's Global Assessment score and sigmoidoscopy score of <or=1, no mucosal friability, and a >or=1 point reduction from baseline in sigmoidoscopy score.Results: Overall, 304 patients who entered this acute extension study were evaluated; 59.5% achieved remission at week 8. Remission rates were similar irrespective of prior treatment in the initial acute phase III studies. CONCLUSIONS: Most patients with mild-to-moderate UC who fail to achieve remission with up to 8 weeks' initial mesalamine therapy can achieve clinical and endoscopic remission following a further 8 weeks' treatment with high-dose MMX mesalamine therapy, thereby avoiding step-up therapy.

Oxelmark L, Hillerås P, Dignass A, Mössner J, Schreiber S, Kruis W, Löfberg R. · Department of Medicine, Karolinska University Hospital, Solna, Sweden. · Scand J Gastroenterol. · Pubmed #17354122 No free full text.

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Schreiber S, Keshavarzian A, Isaacs KL, Schollenberger J, Guzman JP, Orlandi C, Hanauer SB. · Department of General Internal Medicine, Christian-Albrechts University, Schittenhelmstrasse 12, Kiel Schleswig-Holstein 24105, Germany. · Gastroenterology. · Pubmed #17241861 No free full text.

Abstract: BACKGROUND & AIMS: Tetomilast (OPC-6535), a novel thiazole compound, inhibits phosphodiesterase-4 and proinflammatory functions of leukocytes including superoxide production and cytokine release. METHODS: One hundred eighty-six patients with mildly to moderately active ulcerative colitis (Disease Activity Index [DAI] 4-11 points) from 35 centers were randomized to receive an oral, once-daily dose of placebo or tetomilast 25 mg or 50 mg for 8 weeks. RESULTS: Percentages of patients reaching the primary end point (improvement as defined by reduction in DAI > or =3 at week 8) were not significantly different between placebo (35%) and either the 25 mg tetomilast (52%) or the 50 mg tetomilast (39%) groups (intent-to-treat population). Remission rates (DAI 0-1) were 7%, 16%, and 21%, respectively (not significant). Mean reduction in DAI at week 8 was greater in the 25-mg group than under placebo (2.8 +/- 0.4 vs 1.7 +/- 0.36, respectively, P = .041) and approached statistical significance in the 50-mg group (2.8 +/- 0.46, P = .056). A post hoc analysis focusing on patients with high activity scores (baseline DAI 7-11) suggested differences between tetomilast and placebo that will require further investigation. No significant safety concerns were raised. Main adverse effects included gastrointestinal problems (nausea, vomiting) and were preferentially seen in the 50-mg tetomilast group. CONCLUSIONS: This phase II trial of tetomilast in ulcerative colitis did not achieve statistical significance for the primary end point. Secondary end points indicate a potential clinical activity of tetomilast. The post hoc analysis suggests that further clinical development should focus on patients with objective parameters of inflammation.

Kamm MA, Sandborn WJ, Gassull M, Schreiber S, Jackowski L, Butler T, Lyne A, Stephenson D, Palmen M, Joseph RE. · Department of Gastroenterology, St. Mark's Hospital, Watford Road, Harrow, United Kingdom. · Gastroenterology. · Pubmed #17241860 No free full text.

Abstract: BACKGROUND & AIMS: SPD476 (LIALDA in the US; MEZAVANT in the EU; otherwise known as MMX mesalamine; Shire Pharmaceuticals Inc., Wayne, PA, under license from Giuliani SpA, Milan, Italy) is a novel, once-daily, high-strength (1.2 g/tablet) formulation of mesalamine, utilizing MMX Multi Matrix System (MMX) technology designed to deliver the active drug throughout the colon. We performed a double-blind, multicenter study, comparing MMX mesalamine vs placebo for the treatment of active ulcerative colitis. A delayed-release oral mesalamine (ASACOL; Procter & Gamble, Cincinnati, OH) reference arm was included. METHODS: Three hundred forty-three patients with active, mild-to-moderate ulcerative colitis received MMX mesalamine 2.4 g/day or 4.8 g/day given once daily, ASACOL 2.4 g/day given in 3 divided doses, or placebo for 8 weeks. The primary end point was the proportion of patients in clinical and endoscopic remission (modified ulcerative colitis disease activity index of < or =1 with rectal bleeding and stool frequency scores of 0, no mucosal friability, and a > or =1-point reduction in sigmoidoscopy score from baseline). RESULTS: A significantly greater proportion of patients receiving MMX mesalamine 2.4 g/day given once daily (40.5%; P = .01) and 4.8 g/day given once daily (41.2%; P = .007) achieved clinical and endoscopic remission at week 8, vs placebo (22.1%). The clinical and endoscopic remission rate for ASACOL (32.6%; P = .124) was not significantly superior to placebo. All active treatments were well-tolerated. CONCLUSIONS: Once-daily MMX mesalamine was efficacious and well-tolerated for the induction of clinical and endoscopic remission. MMX mesalamine offers effective and convenient mesalamine therapy, potentially improving treatment compliance.

Kruis W, Dignass A, Steinhagen-Thiessen E, Morgenstern J, Mössner J, Schreiber S, Vecchi M, Malesci A, Reinshagen M, Löfberg R. · Evangelisches Krankenhaus Kalk, Innere Abteilung, Universität zu Köln, Germany. · World J Gastroenterol. · Pubmed #16437606 links to  free full text

Abstract: AIM: To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI 6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk). Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn (reg), Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life (IBDQ), and laboratory tests. RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI<4, EI<4). Quality of life (IBDQ) increased significantly (24 points, P<0.01) at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

Musch E, Andus T, Kruis W, Raedler A, Spehlmann M, Schreiber S, Krakamp B, Malek M, Malchow H, Zavada F, Engelberg Feurle G. · Department of Internal Medicine, Marienhospital Bottrop, Bottrop, Germany. · Clin Gastroenterol Hepatol. · Pubmed #15952100 No free full text.

Abstract: BACKGROUND & AIMS: We performed a randomized, double-blind, placebo-controlled, multicenter trial to investigate the efficacy and safety of recombinant interferon-beta-1a (rIFN-beta-1a) in outpatients with active steroid-refractory ulcerative colitis. METHODS: Ninety-one randomized patients subcutaneously received 3 MIU rIFN-beta-1a (group A, n = 32), 1 MIU rIFN-beta-1a (group B, n = 30), or placebo (group C, n = 29) 3 times a week over a period of 8 weeks in addition to standard therapy. An intention-to-treat analysis was performed to evaluate the efficacy and safety of treatment. Results: In all 3 groups, the median prestudy clinical activity index (CAI) was 10. In 18 of 32 patients (56%) in group A, in 11 of 30 patients (36%) in group B, and in 10 of 29 patients (34%) in group C, a reduction of the CAI of 6 points or greater (response) was achieved (differences were not statistically significant). Complete response (reduction of CAI to < or =4) was achieved in 56%, 30%, and 38% of patients in groups A, B, and C, respectively. Compared with baseline, the median endoscopic index had been reduced by 5, 3, and 4 points in groups A, B, and C, respectively. Steroid reduction was 12 mg in group A, 6 mg in group B, and 10 mg in group C. Identical side effects occurred in all 3 groups. Seven serious adverse events were reported (1 in group A and 6 in group C). All were unrelated to therapy as judged by the investigating physicians. CONCLUSIONS: rIFN-beta-1a was safe but not significant, at the dosage and/or duration of treatment used, in steroid-refractory ulcerative colitis. Further studies are indicated.

Nikolaus S, Rutgeerts P, Fedorak R, Steinhart AH, Wild GE, Theuer D, Möhrle J, Schreiber S. · Christian-Albrechts University, Kiel, Germany. · Gut. · Pubmed #12912859 links to  free full text

Abstract: BACKGROUND: and aims: Administration of interferon (IFN)-beta may represent a rational approach to the treatment of ulcerative colitis through its immunomodulatory and anti-inflammatory effects. The present study was performed to evaluate the efficacy and tolerability of IFN-beta-1a. METHODS: Patients (n=18) with moderately active ulcerative colitis were randomised to receive IFN-beta-1a or placebo. IFN-beta-1a was started at a dose of 22 micro g three times a week subcutaneously, and the dose was increased at two week intervals to 44 micro g and then to 88 micro g if no response was observed. The maximum duration of treatment was eight weeks. End points were clinical treatment response, defined as a decrease of at least 3 points from baseline in the ulcerative colitis scoring system (UCSS) symptoms score and induction of endoscopically confirmed remission. RESULTS: Baseline characteristics and disease severity were similar in both groups. Data from 17 patients are included in this report (10 patients in the IFN-beta-1a group and seven patients in the placebo group). Clinical response was achieved in five patients (50%) in the IFN-beta-1a group and in one (14%) in the placebo group (P=0.14). Remission was achieved in three patients in the IFN-beta-1a group and in none in the placebo group (p=0.02). Most adverse reactions associated with IFN-beta-1a were influenza-like symptoms or injection site reactions, and were mild or moderate in severity. CONCLUSIONS: IFN-beta-1a may represent a promising novel treatment approach in ulcerative colitis.

Probert CS, Hearing SD, Schreiber S, Kühbacher T, Ghosh S, Arnott ID, Forbes A. · University Division of Medicine, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, UK. · Gut. · Pubmed #12801957 links to  free full text

Abstract: BACKGROUND: Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis. The benefits of infliximab in Crohn's disease are established. We investigated its efficacy in ulcerative colitis. METHODS: We conducted a randomised placebo controlled trial of infliximab (5 mg/kg) in the treatment of glucocorticoid resistant ulcerative colitis. Infusions were given at weeks 0 and 2. Disease activity and quality of life were recorded over eight weeks of follow up. Remission was defined as an ulcerative colitis symptom score (UCSS) of < or =2 and/or Baron score of 0 at week 6. Patients not in remission were offered open label infliximab 10 mg/kg and reviewed two weeks later. RESULTS: After two weeks, there was no statistically significant difference between the infliximab and placebo groups in the proportion of patients with a Baron score of 0 (13% (3/23) v 5% (1/19) (95% confidence interval (CI) -9% to 24%); p=0.74). After six weeks, remission (UCSS < or =2) rates were 39% (9/23) versus 30% (6/20) (95% CI -19 to 34%; p=0.76). The median improvement in UCSS was 3 for the infliximab group and 2.5 for the placebo group (p=0.82, Mann-Whitney U test). A Baron score of 0 was likely in either group (26% (6/23) v 30% (6/20) (95% CI -30% to 23%); p=0.96). Improvement in the IBDQ and EuroQol was not significantly different between the groups (p=0.22 and 0.3, respectively, Mann-Whitney U test). Twenty eligible patients were given open labelled infusions. Remission was achieved in 3/11 (27%) patients initially treated with infliximab and in 1/9 (11%) patients treated with placebo. CONCLUSION: These data do not support the use of infliximab in the management of moderately active glucocorticoid resistant ulcerative colitis.

Kruis W, Schreiber S, Theuer D, Brandes JW, Schütz E, Howaldt S, Krakamp B, Hämling J, Mönnikes H, Koop I, Stolte M, Pallant D, Ewald U. · Evangelisches Krankenhaus Kalk, Teaching Hospital of the University of Cologne, Germany. · Gut. · Pubmed #11709512 links to  free full text

Abstract: BACKGROUND: Balsalazide is a new 5-aminosalicylic acid (5-ASA) containing prodrug. Its efficacy in comparison with standard mesalazine therapy and the optimum dose for maintaining remission of ulcerative colitis are still unclear. AIMS: To compare the relapse preventing effect and safety profile of two doses of balsalazide and a standard dose of Eudragit coated mesalazine. METHODS: A total of 133 patients with ulcerative colitis in remission were recruited to participate in a double blind, multicentre, randomised trial: 49 patients received balsalazide 1.5 g twice daily, 40 received balsalazide 3.0 g twice daily, and 44 received mesalazine 0.5 g three times daily. Efficacy assessments were clinical activity index (CAI) and endoscopic score according to Rachmilewitz, and a histological score. In addition, laboratory tests were performed and urinary excretion of 5-ASA and its metabolite N-Ac-5-ASA was analysed. The study lasted for 26 weeks. RESULTS: Balsalazide 3.0 g twice daily resulted in a significantly higher clinical remission rate (77.5%) than balsalazide 1.5 g twice daily (43.8%) and mesalazine 0.5 g three times daily (56.8%) (p=0.006). The respective times to relapse were 161 days, 131 days (p=0.003), and 144 days (NS). Accordingly, pairwise contrasts of the final endoscopic score demonstrated a significant difference (p=0.005) between the two balsalazide treatment groups while differences between either of these two groups and mesalazine were not statistically significant. Patients treated with balsalazide excreted less 5-ASA and N-Ac-5-ASA than patients receiving mesalazine but these differences were not statistically significant. Discontinuation of the trial because of adverse effects occurred in nine patients: three in the balsalazide 1.5 g twice daily group, two in the balsalazide 3.0 g twice daily group, and four in the mesalazine 0.5 g three times daily group. No clinically important new drug safety related findings were identified in this study. CONCLUSIONS: High dose balsalazide (3.0 g twice daily) was superior in maintaining remission in patients with ulcerative colitis compared with a low dose (1.5 g twice daily) or a standard dose of mesalazine (0.5 g three times daily). All three treatments were safe and well tolerated.

Bregenzer N, Caesar I, Andus T, Hämling J, Malchow H, Schreiber S, Schölmerich J. · Department of Internal Medicine University of Regensburg. · Z Gastroenterol. · Pubmed #10549094 No free full text.

Abstract: Patients with active ulcerative colitis have decreased levels of factor XIII (FXIII) activity, which is important for woundhealing. Recent uncontrolled studies claimed a beneficial effect of Factor XIII on clinical symptoms of ulcerative colitis, in particular intestinal bleeding. The objective of this trial was to evaluate the benefits of additional FXIII treatment in steroid-refractory patients with ulcerative colitis in a prospective, double blind, placebo-controlled study. A total of 28 patients were enrolled between October 1994 and January 1997. Primary objective of this study was the time until cessation of visible intestinal bleeding with 14 days after the start of treatment. Patients were treated for ten days either by i.v. application of FXIII concentrate or by placebo. The analysis of the primary efficacy criterion, cessation of intestinal bleeding, by a planned interim analysis showed no significant differences between the treatment groups (p = 0.8). This resulted in the termination of the study. The same applied to the CAI score. No patient in both treatment groups reached remission according to the colo-/-sigmoidoscopy score. Due to the high number of patients (16 of 28) who had to be excluded from the per-protocol analysis (e.g. changes to the concomitant medication) only the intention-to-treat population was analyzed. Overall the study showed no beneficial effect of additional FXIII treatment on active steroid-refractory ulcerative colitis. These results do not confirm previous open label studies which had reported a significant improvement of clinical symptoms.