Universitatsklinik For Innere Medizin Iii

Innsbruck, Austria

Universitatsklinik For Innere Medizin Iii

Innsbruck, Austria

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Keshav S.,University of Oxford | Vanasek T.,Hepato Gastroenterologie HK | Niv Y.,Rabin Medical Center | Petryka R.,NZOZ Vivamed | And 11 more authors.
PLoS ONE | Year: 2013

CCX282-B, also called vercirnon, is a specific, orally-administered chemokine receptor CCR9 antagonist that regulates migration and activation of inflammatory cells in the intestine. This randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of CCX282-B in 436 patients with Crohn's disease. Crohn's Disease Activity Index (CDAI) scores were 250-450 and C-reactive protein >7.5 mg/L at study entry. In addition to stable concomitant Crohn's medication (85% of subjects), subjects received placebo or CCX282-B (250 mg once daily, 250 mg twice daily, or 500 mg once daily) for 12 weeks. They then received 250 mg CCX282-B twice daily, open-label, through week 16. Subjects who had a clinical response (a ≥70 point drop in CDAI) at week 16 were randomly assigned to groups given placebo or CCX282-B (250 mg, twice daily) for 36 weeks. Primary endpoints were clinical response at Week 8 and sustained clinical response at Week 52. During the 12-week Induction period, the clinical response was highest in the group given 500 mg CCX282-B once daily. Response rates at week 8 were 49% in the placebo group, 52% in the group given CCX282-B 250 mg once daily (odds ratio [OR] = 1.12; p =. 667 vs placebo), 48% in the group given CCX282-B 250 mg twice daily (OR = 0.95; p =. 833), and 60% in the group given CCX282-B 500 mg once daily (OR = 1.53; p =. 111). At week 12, response rates were 47%, 56% (OR = 1.44; p =. 168), 49% (OR = 1.07; p =. 792), and 61% (OR = 1.74; p =. 039), respectively. At the end of the Maintenance period (week 52), 47% of subjects on CCX282-B were in remission, compared to 31% on placebo (OR = 2.01; p =. 012); 46% showed sustained clinical responses, compared to 42% on placebo (OR = 1.14; p =. 629). CCX282-B was well tolerated. Encouraging results from this clinical trial led to initiation of Phase 3 clinical trials in Crohn's disease. Trial Registration: ClinicalTrials.gov NCT00306215. © 2013 Keshav et al.


Ferenci P.,Medical University of Vienna | Ferenci P.,Universitatsklinik For Innere Medizin Iii | Laferl H.,Kaiser Franz Josef Spital | Scherzer T.,Medical University of Vienna | And 12 more authors.
Gastroenterology | Year: 2010

Background & Aims: This randomized multicenter trial evaluated individualization of treatment duration with peginterferon alfa-2a 180 μg/wk plus ribavirin 1000/1200 mg/day in patients with chronic hepatitis C genotype 1/4 based on the rapidity of virologic response (VR). Methods: Patients with a rapid VR (RVR; undetectable hepatitis C virus [HCV]-RNA level (<50 IU/mL at week 4) were treated for 24 weeks, those with an early VR (EVR; no RVR but undetectable HCV-RNA level or ≥2-log10 decrease at week 12) were randomized to 48 (group A) or 72 weeks of treatment (group B; peginterferon alfa-2a was reduced to 135 μg/wk after week 48). Patients without an EVR continued treatment until week 72 if they had undetectable HCV-RNA levels at week 24. The primary end point was relapse; sustained VR (SVR; undetectable HCV-RNA level after 24 weeks of follow-up evaluation) was a secondary end point. Results: Of 551 genotype 1/4 patients starting treatment, 289 were randomized to group A (N = 139) or group B (N = 150). The relapse rate was 33.6% in group A (95% confidence interval [CI], 24.8%-43.4%) and 18.5% in group B (95% CI, 11.9%-27.6%; P = .0115 vs group A) and the SVR rate was 51.1% (95% CI, 42.5%-59.6%) and 58.6% (95% CI, 50.3%-66.6%; P > .1), respectively. The overall SVR rate was 50.4% (278 of 551; 95% CI, 46.2%-54.7%), including 115 of 150 patients with an RVR treated for 24 weeks and 4 of 78 patients without an EVR. Conclusions: Extending therapy with peginterferon alfa-2a/ribavirin to 72 weeks decreases the probability of relapse in patients with an EVR. If they can be maintained on extended-duration therapy, SVR rates also may improve. © 2010 AGA Institute.


Abrahamian H.,Internistisches Zentrum | Kautzky-Willer A.,Universitatsklinik For Innere Medizin Iii
Wiener Medizinische Wochenschrift | Year: 2016

The association between obesity and sexual dysfunction has been described in many studies. Neurobiological, hormonal, vascular and mental disturbances are the main reasons in male and in female gender. Sexual interest and desire, sexual arousal, orgasm, painful intercourse and premature ejaculation can be involved. Data for prevalence of sexual function disturbances in obese people are scarce and most studies were small. For screening of sexual function we recommend the International Index of Erectile Function (IIEF)-Score, which contains 15 Items for males and the Female Sexual Function Index (FSFI), which contains 19 items for females. Treatment of sexual function disturbances include lifestyle changes with an increase of physical activity, weight control, healthy eating and smoking cessation. Testosterone substitution in cases of real hypogonadism and treatment with PDE-5 inhibitors are well documented treatment options in male individuals. New treatment options for female patients with variable effectiveness are fibanserin, testosterone, bupropione and oxytocin. © 2016, Springer-Verlag Wien.


Zeuzem S.,Goethe University Frankfurt | Berg T.,University of Leipzig | Gane E.,Auckland Clinical Studies | Ferenci P.,Universitatsklinik For Innere Medizin Iii | And 15 more authors.
Gastroenterology | Year: 2014

Background & Aims Simeprevir (TMC435) is an oral NS3/4 protease inhibitor in phase III trials for chronic hepatitis C virus (HCV) infection. We performed a phase IIb, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the combination of simeprevir, peginterferon-α2a (PegIFN), and ribavirin (RBV) in patients with HCV genotype-1 infection previously treated with PegIFN and RBV. Methods We analyzed data from patients who did not respond (null response), had a partial response, or relapsed after treatment with PegIFN and RBV, randomly assigned to receive simeprevir (100 or 150 mg, once daily) for 12, 24, or 48 weeks plus PegIFN and RBV for 48 weeks (n = 396), or placebo plus PegIFN and RBV for 48 weeks (n = 66). All patients were followed for 24 weeks after planned end of treatment; the primary end point was the proportion of patients with sustained virologic response (SVR; undetectable HCV RNA) at that time point. Results Overall, rates of SVR at 24 weeks were significantly higher in the groups given simeprevir than those given placebo (61%-80% vs 23%; P <.001), regardless of prior response to PegIFN and RBV (simeprevir vs placebo: prior null response, 38%-59% vs 19%; prior partial response, 48%-86% vs 9%; prior relapse, 77%-89% vs 37%). All groups had comparable numbers of adverse events; these led to discontinuation of simeprevir or placebo and/or PegIFN and RBV in 8.8% of patients given simeprevir and 4.5% of those given placebo. Conclusions In treatment-experienced patients, 12, 24, or 48 weeks simeprevir (100 mg or 150 mg once daily) in combination with 48 weeks PegIFN and RBV significantly increased rates of SVR at 24 weeks compared with patients given placebo, PegIFN, and RBV and was generally well tolerated. ClinicalTrials.gov number: NCT00980330. © 2014 by the AGA Institute.


PubMed | Internistisches Zentrum and Universitatsklinik For Innere Medizin Iii
Type: Journal Article | Journal: Wiener medizinische Wochenschrift (1946) | Year: 2016

The association between obesity and sexual dysfunction has been described in many studies. Neurobiological, hormonal, vascular and mental disturbances are the main reasons in male and in female gender. Sexual interest and desire, sexual arousal, orgasm, painful intercourse and premature ejaculation can be involved. Data for prevalence of sexual function disturbances in obese people are scarce and most studies were small. For screening of sexual function we recommend the International Index of Erectile Function (IIEF)-Score, which contains 15 Items for males and the Female Sexual Function Index (FSFI), which contains 19 items for females. Treatment of sexual function disturbances include lifestyle changes with an increase of physical activity, weight control, healthy eating and smoking cessation. Testosterone substitution in cases of real hypogonadism and treatment with PDE-5 inhibitors are well documented treatment options in male individuals. New treatment options for female patients with variable effectiveness are fibanserin, testosterone, bupropione and oxytocin.


Sandborn W.J.,University of California at San Diego | Feagan B.G.,University of Western Ontario | Marano C.,Janssen Research and Development LLC | Zhang H.,Janssen Research and Development LLC | And 11 more authors.
Gastroenterology | Year: 2014

Background & Aims Subcutaneous golimumab, a fully human monoclonal antibody to tumor necrosis factor-α (TNFα), was evaluated as maintenance therapy in TNFα antagonist-naive adults with moderate-to-severe active ulcerative colitis, despite conventional therapy, who responded to golimumab induction therapy. Methods We performed a phase 3, double-blind trial of patients who completed golimumab induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment, eg, PURSUIT). Patients who responded to induction therapy with golimumab (n = 464) were assigned randomly to groups given placebo or injections of 50 or 100 mg golimumab every 4 weeks through week 52. Patients who responded to placebo in the induction study continued to receive placebo. Nonresponders in the induction study received 100 mg golimumab. The primary end point was clinical response maintained through week 54; secondary end points included clinical remission and mucosal healing at both weeks 30 and 54. Results Clinical response was maintained through week 54 in 47.0% of patients receiving 50 mg golimumab, 49.7% of patients receiving 100 mg golimumab, and 31.2% of patients receiving placebo (P =.010 and P <.001, respectively). At weeks 30 and 54, a higher percentage of patients who received 100 mg golimumab were in clinical remission and had mucosal healing (27.8% and 42.4%) than patients given placebo (15.6% and 26.6%; P =.004 and P =.002, respectively) or 50 mg golimumab (23.2% and 41.7%, respectively). Percentages of serious adverse events were 7.7%, 8.4%, and 14.3% among patients given placebo, 50 mg, or 100 mg golimumab, respectively; percentages of serious infections were 1.9%, 3.2%, and 3.2%, respectively. Among all patients given golimumab in the study, 3 died (from sepsis, tuberculosis, and cardiac failure, all in patients who received 100 mg golimumab) and 4 developed active tuberculosis. Conclusions Golimumab (50 mg or 100 mg) maintained clinical response through week 54 in patients who responded to induction therapy with golimumab and had moderate-to-severe active ulcerative colitis; patients who received 100 mg golimumab had clinical remission and mucosal healing at weeks 30 and 54. Safety was consistent with that reported for other TNFα antagonists and golimumab in other approved indications. ClinicalTrials.gov number: NCT00488631. © 2014 by the AGA Institute.


Sandborn W.J.,University of California at San Diego | Feagan B.G.,University of Western Ontario | Marano C.,Janssen Research and Development LLC | Zhang H.,Janssen Research and Development LLC | And 12 more authors.
Gastroenterology | Year: 2014

Background & Aims Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) -α, for treatment of ulcerative colitis (UC). We evaluated subcutaneous golimumab induction therapy in TNF-α antagonist-naïve patients with moderate-to-severe UC despite conventional treatment. Methods We integrated double-blind phase 2 dose-finding and phase 3 dose-confirmation trials in a study of 1064 adults with UC (Mayo score: 6-12; endoscopic subscore ≥2; 774 patients in phase 3). Patients were randomly assigned to groups given golimumab doses of 100 mg and then 50 mg (phase 2 only), 200 mg and then 100 mg, or 400 mg and then 200 mg, 2 weeks apart. The phase 3 primary end point was week-6 clinical response. Secondary end points included week-6 clinical remission, mucosal healing, and Inflammatory Bowel Disease Questionnaire (IBDQ) score change. Results In phase 2, median changes from baseline in the Mayo score were -1.0, -3.0, -2.0, and -3.0, in the groups given placebo, 100 mg/50 mg, 200/100 mg, and 400/200 mg golimumab, respectively. In phase 3, rates of clinical response at week 6 were 51.0% and 54.9% among patients given 200 mg/100 mg and 400 mg/200 mg golimumab, respectively, vs 30.3% among those given placebo (both, P ≤.0001). Rates of clinical remission and mucosal healing and mean changes in IBDQ scores were significantly greater in both golimumab groups vs the placebo group (P ≤.0014, all comparisons). Rates of serious adverse events were 6.1% and 3.0%, and rates of serious infection were 1.8% and 0.5%, in the placebo and golimumab groups, respectively. One patient in the 400 mg/200 mg group died as a result of surgical complications of an ischiorectal abscess. Conclusions Treatment with subcutaneous golimumab induces clinical response, remission, and mucosal healing, and increases quality of life in larger percentages of patients with active UC than placebo. ClinicalTrials.gov Number: NCT00487539. © 2014 by the AGA Institute.


Reinisch W.,Universitatsklinik For Innere Medizin Iii | Angelberger S.,Universitatsklinik For Innere Medizin Iii | Petritsch W.,Medical University of Graz | Shonova O.,Nemocnice Ceske Budejovice | And 11 more authors.
Gut | Year: 2010

Objective: 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 severe endoscopic recurrence. Methods: 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 ≥200 and an increase of ≥60 points from baseline, or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction. Results: 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 ≥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). Conclusions: 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. Clinical trial registration number NCT00946946.


Jung J.J.,University of Rostock | Husse B.,Universitatsklinik For Innere Medizin Iii | Husse B.,Ludwig Maximilians University of Munich | Rimmbach C.,University of Rostock | And 7 more authors.
Stem Cell Reports | Year: 2014

Therapeutic approaches for "sick sinus syndrome" rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via "biological pacemakers" derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300-400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro. © 2014 The Authors.


Krebs M.,Universitatsklinik For Innere Medizin Iii
Austrian Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Calcitonin (CT) measurement is crucial to the early diagnosis and the follow-up of medullary thyroid cancer (MTC). If the evaluation of stimulated CT levels is required, a provocative test can be performed, being the high-dose Ca test recently reintroduced in clinical practice. Objective: Our objective was to identify gender-specific thresholds for MTC diagnosis in a large series of patients who underwent the Ca test. Patients and Methods: A total of 91 patients (49 females and 42 males) underwent the Ca test (calcium gluconate, 25 mg/kg) before thyroidectomy and both basal CT (bCT) and stimulated CT (sCT) were compared with histological results by receiver operating characteristic plot analyses. To evaluate possible side effects of Ca administration, cardiac function has been extensively studied. Results: bCT levels were found to harbor the same accuracy as sCT in the preoperative diagnosis of MTC. The best Ca thresholds for the identification of MTC were >26 and >68 for bCT and >79 and >544 pg/mL for sCT in females and males, respectively. The high tolerability and safety of the Ca test was demonstrated and advice offered to be followed before and during the test. Conclusions: Gender-specific bCT and sCT cutoffs for the identification of C-cell hyperplasia and/or MTC have been defined. The bCT and sCT were found to have a similar accuracy, indicating that serum CT assays with improved functional sensitivity may likely decrease the relevance of the stimulation test in several conditions. Finally, systematic cardiac monitoring confirms the safety of the Ca test. © 2014, J KLIN ENDOKRINOL STOFFW. All rights reserved.

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