A new mesalazine foam enema (Claversal Foam) compared with a standard liquid enema in patients with active distal ulcerative colitis

BACKGROUND: Rectally administered mesalazine (5-aminosalicylic acid) is a recognized therapy for distal ulcerative colitis. It is frequently applied as a liquid enema. However, there are reasons (acceptability to the patient, more uniform topical dispersion and effective adhesion) to prefer a foam-based enema. AIM: This study compared a foam enema (2 g mesalazine per day, Claversal Foam) with a standard liquid enema (4 g mesalazine per day, Salofalk enema). METHODS: Patients with active distal ulcerative colitis, diagnosed according to standardized criteria, were treated for 4 weeks. The primary goal was clinical remission; endoscopic remission, histological changes, global assessment and standard safety measures were also analysed. A major subset of the patients also provided quality-of-life data. RESULTS: Both foam and liquid enema gave good rates of clinical and endoscopic remission. The foam enema was shown to be as efficacious as the reference, even though the daily dose in the foam treatment contained only half as much active drug as in the reference treatment. Minor regional differences in efficacy were seen. The tolerabilities of the two formulations were comparable. CONCLUSIONS: The foam enema offers a safe, efficacious and acceptable treatment for distal ulcerative colitis.     

Oral versus combination mesalazine therapy in active ulcerative colitis: a double-blind, double-dummy, randomized multicentre study

BACKGROUND: Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment. AIM: To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis. METHODS: Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4-12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI < 4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end-points; the rate of endoscopic remission was a secondary end-point. RESULTS: 67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention-to-treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively. CONCLUSIONS: In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission.     

Colonic spreading of a non-chlorofluorocarbon mesalazine rectal foam enema in patients with quiescent ulcerative colitis

Background: Rectal foam enemas provide for drug delivery to the distal colon for treatment of left sided ulcerative colitis. However, currently available formulations contain chlorofluorocarbons which are due to be phased out in the near future. The objective of this study was therefore to determine the degree of dispersion of a newly developed nonchlorofluorocarbon rectal foam preparation in ulcerative colitis patients. Methods: This was an open label non-controlled study of a single administration of a mesalazine foam enema (two actuations containing 2 g of mesalazine in approximately 120 mL foam) in 10 patients with quiescent ulcerative colitis. Spreading of the ^99mTc-labelled foam enema was assessed over a 4-h period by the non-invasive technique of gamma scintigraphy. Results: All patients retained the enema for the full 4-h imaging period. In nine out of the 10 patients, the enema was observed to spread as far as the descending colon and on average 23% of the dose was present in the descending colon at 4 h post-dose. Conclusions: The extent of spreading observed in the study supports the use of the formulation in the treatment of left sided ulcerative colitis.     

Retrograde colonic spread of a new mesalazine rectal enema in patients with distal ulcerative colitis

Background : Rectal treatment with mesalazine enemas is the first-line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5-ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema.
Methods : Twelve patients with active ulcerative colitis were administered 4 g of the mesalazine rectal enema labelled with 100 MBq technetium sulphur colloid (^99mTc-SC). Anterior scans of the abdomen were acquired at intervals for 4 h. Scans were analysed to evaluate the extent of retrograde flow and homogeneity of distribution of the radiolabelled enema in the rectum, sigmoid, descending and transverse colon. In addition, plasma levels of 5-ASA and Ac-5-ASA were measured for 6 h.
Results : All patients retained the entire rectal gel throughout the course of the study without reporting adverse events. In 11 out of 12 patients (92%) the gel had spread homogeneously beyond the sigmoid colon and had reached the upper limit of disease in all cases. The maximum spread (splenic flexure) was observed in 6 out of 12 patients (50%) within the first 2 h. The systemic absorption of mesalazine and its metabolite Ac-5-ASA was low.
Conclusions : The new mesalazine enema represents an adequate alternative and a further technological improvement in the topical treatment of distal ulcerative colitis.     

Safety and efficacy of two dose formulations of alicaforsen enema compared with mesalazine enema for treatment of mild to moderate left-sided ulcerative colitis: a randomized, double-blind, active-controlled trial

BACKGROUND: Alicaforsen is an antisense oligonucleotide inhibitor of intercellular adhesion molecule 1 protein expression with activity in subjects with ulcerative colitis and pouchitis. AIM: To compare the effects of alicaforsen enema to standard of care mesalazine (mesalamine) enema in subjects with mild to moderate active left-sided ulcerative colitis. METHOD: A randomized, double-blind, active-controlled multicentre clinical trial. Subjects received a nightly enema of 120 mg alicaforsen (n=55), 240 mg alicaforsen (n=50), or 4 g mesalazine (n=54) for 6 weeks, followed by a 24-week monitoring period. The primary end point was Disease Activity Index at week 6. Clinical improvement, remission and relapse were secondary end points. RESULTS: No significant difference was observed between treatment arms in the primary end point. However, the median duration of response to alicaforsen enema treatment was two- to threefold longer (128 and 146 days) in comparison with mesalazine (54 days). Complete mucosal healing occurred in 24% of the 240 mg alicaforsen group, when compared with 17% in the mesalazine. CONCLUSIONS: Alicaforsen enema demonstrated an acute response and safety profile similar to mesalazine enema, but was differentiated by a more durable response. The extended length of remission suggests that alicaforsen enema treatment may have a disease modifying effect.     

美沙拉嗪口服联合灌肠治疗溃疡性结肠炎120例疗效观察

目的观察美沙拉嗪口服联合灌肠治疗溃疡性结肠炎的疗效。方法选择240例轻、中度溃疡性结肠炎患者,随机分为两组:治疗组120例予口服美沙拉嗪,1.0g/次,3次/d,同时给予美沙拉嗪灌肠剂(莎尔福灌肠剂,4g/60ml,用时稀释到100ml)4g/100ml,1次/晚,保留灌肠,8周为1疗程;对照组120例,予口服柳氮磺吡啶片(Alicylazosulfapyridine,SASP)1.0g,4次/d。疗程为8周。结果治疗8周后,治疗组显效率和总有效率明显优于对照组,差异有统计学意义(P<0.05);两组均有不良反应的发生,治疗组发生13例,发生率10.8%,对照组发生68例,发生率56.7%,治疗组明显低于对照组,差异有统计学意义(P<0.05)。结论美沙拉嗪了治疗溃疡性结肠炎临床疗效显著,且不良反应小。     

A new mesalazine gel enema in the treatment of left-sided ulcerative colitis: a randomized controlled multicentre trial

BACKGROUND: A new mesalazine rectal gel preparation (without propellant gas) has been recently developed to improve topical treatment in distal ulcerative colitis. AIM: To evaluate the efficacy, safety and patient tolerability of mesalazine gel enema compared with mesalazine foam enema in the treatment of patients with acute left-sided ulcerative colitis. METHODS: In a randomized multicentre investigator-blind parallel group trial, 103 patients with mild to moderate left-sided colitis or proctosigmoiditis were randomly allocated to mesalazine 2 g gel enema (n = 50 evaluable patients) and mesalazine 2 g foam enema (n = 53 evaluable patients) for 4 weeks. Clinical symptoms, endoscopic and histological findings were assessed at entry, 2 and 4 weeks. Patients' evaluation of treatment tolerability and acceptability was assessed at 2 and 4 weeks. RESULTS: After 4 weeks of treatment, clinical remission was achieved by 76% of mesalazine gel enema-treated patients and 69% of patients treated with mesalazine foam enema (P = 0.608). Endoscopic remission rates at week 4 were 51 and 52% for the mesalazine gel and foam enemas, respectively (P = 0.925). Histological remission was achieved by 30% of patients in both groups. Patients reported that the new mesalazine gel preparation was significantly better tolerated than the foam enema. Patients in the foam group had significantly more difficulty in retention (25% vs. 6%, P < 0.05), abdominal bloating (50% vs. 26%, P < 0.005) and discomfort during administration (48% vs. 26%, P < 0.05). CONCLUSION: The new mesalazine gel enema is efficacious and significantly better tolerated than the mesalazine foam enema.     

Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized,double-blind,placebo-controlled,dose-escalation trial

BACKGROUND: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. AIM: To evaluate repifermin for the treatment of active ulcerative colitis. METHODS: Eighty-eight patients with active ulcerative colitis were enrolled in a 6-week, double-blind trial. Patients were randomized to receive treatment for five consecutive days with intravenous repifermin at a dose of 1, 5, 10, 25 or 50 microg/kg, or placebo. The primary objective of the study was to evaluate the safety of repifermin. The primary efficacy outcome was clinical remission at week 4, defined as a score of zero on the endoscopic appearance and stool blood components of the Mayo score and a score of zero or unity on the stool frequency and physician's global assessment components. RESULTS: At week 4, the rates of clinical remission in the 1, 5, 10, 25 and 50 microg/kg repifermin groups were 19%, 9%, 0%, 0% and 0%, respectively, and 11% for the placebo group (P = 0.32 for repifermin vs. placebo). The frequencies of commonly occurring adverse events and severe adverse events were similar in both groups. CONCLUSIONS: Intravenous repifermin at a dose of 1-50 microg/kg was very well tolerated, but there was no evidence that repifermin was effective for the treatment of active ulcerative colitis at these doses. An additional study to determine the efficacy of repifermin at doses of > 50 microg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.     

MMX Multi Matrix System mesalazine for the induction of remission in patients with mild-to-moderate ulcerative colitis: a combined analysis of two randomized, double-blind, placebo-controlled trials

BACKGROUND: MMX mesalazine [LIALDA (US), MEZAVANT XL (UK and Ireland) MEZAVANT (elsewhere)] utilizes MMX Multi Matrix System (MMX) technology which delivers mesalazine throughout the colon. Two phase III studies have already evaluated MMX mesalazine in patients with active, mild-to-moderate ulcerative colitis. Aim To provide more precise estimates of the efficacy of MMX mesalazine over placebo by combining the patient populations from the two phase III studies. Methods Combined data from two 8-week, double-blind, placebo-controlled trials were analyzed. Patients randomized to MMX mesalazine 2.4 g/day (once daily or 1.2 g twice daily), 4.8 g/day (once daily) or placebo were reviewed. The primary end point was clinical and endoscopic remission (modified Ulcerative Colitis-Disease Activity Index of /=1-point reduction in sigmoidoscopy score from week 0). Results Data from 517 patients were analysed. 8-week remission rates were 37.2% and 35.1% in the MMX mesalazine 2.4 g/day and 4.8 g/day groups, vs. 17.5% on placebo (P < 0.001, both comparisons). 8-week complete mucosal healing rates were 32% in both MMX mesalazine groups compared with 16% on placebo. Adverse event frequency was similar in all groups. Conclusion MMX mesalazine is effective and generally well tolerated for inducing clinical and endoscopic remission of active, mild-to-moderate ulcerative colitis.     

Retrograde spread of mesalazine (5-aminosalicylic acid)-containing enema in patients with ulcerative colitis

In order to investigate the retrograde spread in the colon and its relationship to the extent of the diseased area, the authors evaluated a 100ml enema of mesalazine (5-aminosalicylic acid, Pentasa') lg in a consecutive series of 30 patients with ulcerative colitis. The enema was labelled with 10 MBq 99mtechnetium-human serum albumin microcolloid. Sequential scintigraphic imaging was performed in all patients, and the results compared with the extension of the disease as found by colonoscopy. If the enema reached the entire affected area it was interpreted as 'topically adequate'. In 80% of the patients there was retrograde spread of the enema beyond the rectosigmoid, thus reaching the affected area in ulcerative colitis. No relationship was found between the extent of dispersion of the enema and the time of defecation prior to scintigraphy. The authors conclude that a 100ml 'Pentasa' enema may be adequate for treatment of ulcerative colitis extending up to the splenic flexure.     

Clinical trial: randomized-controlled clinical study comparing the efficacy and safety of a low-volume vs. a high-volume mesalazine foam in active distal ulcerative colitis

BACKGROUND: Rectally administered mesalazine (mesalamine; 5-aminosalicylic acid) is the first-line therapy for treatment of distal ulcerative colitis. Recently, a high-volume 5-aminosalicylic acid foam has been shown to be as effective and safe as standard 5-aminosalicylic acid enema. AIM: To study the efficacy and safety of a low-volume vs. a high-volume 5-aminosalicylic acid foam. METHODS: In this investigator-blinded study, patients with active distal ulcerative colitis [Clinical Activity Index (CAI) > 4, Endoscopic Index > or = 4] were randomized to receive 2 x 1 g/30 mL low-volume (n = 163) or 2 x 1 g/60 mL high-volume 5-aminosalicylic acid foam (n = 167) for 42 days. Primary end point was clinical remission (CAI < or = 4) at the final/withdrawal visit (per-protocol). RESULTS: 330 patients were evaluable for efficacy and safety by intention-to-treat, 290 for per-protocol analysis. Clinical remission rates at week 6 (per-protocol) were 77% on low-volume foam vs. 77% on high-volume foam (P = 0.00002 for non-inferiority). The low-volume foam was associated with a lower frequency of severe discomfort, pain and retention problems. CONCLUSIONS: Low-volume 5-aminosalicylic acid foam is as effective and safe as a high-volume 5-aminosalicylic acid foam in the treatment of active distal ulcerative colitis, but offers compliance advantages compared to the high-volume preparation.     

Oral beclometasone dipropionate in the treatment of active ulcerative colitis: a double-blind placebo-controlled study

AIM: To evaluate efficacy and safety of oral beclometasone dipropionate (BDP) when added to 5-ASA in the treatment of patients with active ulcerative colitis. METHODS: In a 4-week, placebo-controlled, double-blind study, patients with extensive or left-sided mild to moderate active ulcerative colitis were randomized to receive oral 5-ASA (3.2 g/day) plus BDP (5 mg/day) or placebo. Clinical, endoscopic and histologic features, and haematochemical parameters were recorded at baseline and at the end of the study. RESULTS: One hundred and nineteen patients were enrolled and randomly treated with BDP plus 5-ASA (n = 58) or placebo plus 5-ASA (n = 61). Both treatment groups showed a statistically significant decrease of disease activity index (DAI) and histology score at the end of treatment (P = 0.001, each). DAI score was lower in the BDP group than in the placebo group (P = 0.014), with more patients in clinical remission in the BDP group (58.6% vs. 34.4%, P = 0.008). Serum cortisol levels significantly decreased in BDP group vs. baseline (P = 0.002), but without signs of pituitary-adrenal function depletion. A low incidence of adverse events was observed in both groups. CONCLUSIONS: Oral BDP in combination with oral 5-ASA is significantly more effective than 5-ASA alone in the treatment of patients with extensive or left-sided active ulcerative colitis.     

Efficacy and safety of topical hirudin (Hirudex): a double-blind, placebo-controlled study

Hirudin, a thrombin inhibitor isolated from the leech Hirudo medicinalis, has been long known for its anticoagulant effects. In 1990, the former German BGA has published a monograph on Hirudo medicinalis extract (containing Hirudin and Eglin), stating that its local use is indicated in bruises with or without hematoma. The aim of this double-blind, placebo-controlled clinical trial was to evaluate the efficacy and safety of a Hirudin-containing cream (Hirudex cream; Hirudo medicinalis extract 280 UI/100 g) in patients affected with bruises with or without hematoma. 60 men and women between the ages of 18 and 65 years with a unilateral acute musculoskeletal injury (bruise) with or without hematoma were included. Dosage schedule and application route for both treatments were the following: 3-4 daily applications for 5 days for a total of 15-20 administrations during the whole study period. In the Hirudin group, a highly statistically and clinically significant improvement were noted. Although a statistical improvement was also seen in patients treated with placebo, this was less pronounced, and a highly significant between-group difference was noted for all three major efficacy parameters at each follow-up visit in favour of Hirudin. Both the patients and the investigator considered the overall assessment of efficacy at the end of the study to be significantly better (p < 0.001) in the Hirudin group than in the placebo group. Results of this study suggest that Hirudin is an effective local treatment in patients with mild to moderate bruises.     

Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized,double-blind,placebo-controlled trial

Abstract

Objective:

Type 2 diabetes in the elderly is an important and insufficiently studied public health problem. This study evaluated sitagliptin monotherapy in patients with type 2 diabetes aged ≥65 years.     

Gastrointestinal tolerability of meloxicam and piroxicam: a double-blind placebo-controlled study

Aims The aim of the study was to compare the effects of meloxicam and piroxicam on the gastroduodenal mucosa in healthy adults.
Methods Forty-four healthy volunteers were given a 28 day course of either meloxicam 15  mg, piroxicam 20  mg or placebo. Damage to the oesophageal, gastric and duodenal mucosa was assessed, mucosal blood flow (MBF) measured at endoscopy and biopsies taken for prostaglandin content and microscopic assessment of damage before NSAID administration and during days 1, 7 and 28 of continued intake.
Results Maximal macroscopic gastric mucosal damage (median grade+IQR) occurred within 24  h of piroxicam administration, the damage score increasing from 0 to 2.5 (0–3) ( P =0.02) at day 1 before falling to 2.0 (0–2) at day 7 and 0 (0–1) at day 28 with resolution of damage observed in six out of the seven subjects who sustained acute injury. No significant macroscopic gastric damage occurred in either of the two other groups although some minor damage was observed in seven subjects taking placebo and five taking meloxicam. There was a trend towards piroxicam causing more acute gastric damage than meloxicam ( P =0.06). Baseline antral, body and duodenal MBF were similar in all three groups. No significant changes occurred in any of the groups on any of the visits. There were also no changes in gastric mucosal prostaglandin content in any group.
Conclusions These observations suggest that meloxicam causes little acute damage to the upper gastrointestinal tract and piroxicam causes some acute gastric injury but such damage resolves in most subjects by 28 days.     

盐酸小檗碱片联合美沙拉嗪治疗远端溃疡性结肠炎的临床研究

目的探讨盐酸小檗碱片联合美沙拉嗪治疗远端溃疡性结肠炎的临床疗效。方法收集泰州市中西医结合医院2015年1月—2017年12月收治远端溃疡性结肠炎的患者80例,随机分为对照组和治疗组,每组各40例。对照组口服美沙拉嗪缓释颗粒剂,1.0 g/次,4次/d。治疗组在对照组治疗基础上口服盐酸小檗碱片,0.2 g/次,3次/d。两组患者均连续治疗2个月。观察两组患者临床疗效,同时比较治疗前后两组患者症状消失时间和炎症因子。结果治疗后,对照组和治疗组临床有效率分别为75.00%和92.50%,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组患者腹痛、腹泻和脓血便的临床症状消失时间明显早于对照组患者,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者炎症指标白细胞介素-6(IL-6)、IL-8和肿瘤坏死因子-α(TNF-α)较治疗前显著降低(P0.05),IL-10较治疗前显著升高(P0.05),且治疗组IL-6、IL-8和IL-10水平明显好于对照组(P0.05)。结论盐酸小檗碱片联合美沙拉嗪治疗远端溃疡性结肠炎患者效果显著,尤其在减轻炎症因子方面优势明显,具有一定的临床推广应用价值。