Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study.

OBJECTIVES: VSL#3 is a high-potency probiotic mixture that has been used successfully in the treatment of pouchitis. The primary end point of the study was to assess the effects of supplementation with VSL#3 in patients affected by relapsing ulcerative colitis (UC) who are already under treatment with 5-aminosalicylic acid (ASA) and/or immunosuppressants at stable doses. METHODS: A total of 144 consecutive patients were randomly treated for 8 weeks with VSL#3 at a dose of 3,600 billion CFU/day (71 patients) or with placebo (73 patients). RESULTS: In all, 65 patients in the VSL#3 group and 66 patients in the placebo group completed the study. The decrease in ulcerative colitis disease activity index (UCDAI) scores of 50% or more was higher in the VSL#3 group than in the placebo group (63.1 vs. 40.8; per protocol (PP) P=0.010, confidence interval (CI)95(%) 0.51-0.74; intention to treat (ITT) P=0.031, CI95(%) 0.47-0.69). Significant results with VSL#3 were recorded in an improvement of three points or more in the UCDAI score (60.5% vs. 41.4%; PP P=0.017, CI95(%) 0.51-0.74; ITT P=0.046, CI95(%) 0.47-0.69) and in rectal bleeding (PP P=0.014, CI95(%) 0.46-0.70; ITT P=0.036, CI95(%) 0.41-0.65), whereas stool frequency (PP P=0.202, CI95(%) 0.39-0.63; ITT P=0.229, CI95(%) 0.35-0.57), physician's rate of disease activity (PP P=0.088, CI95(%) 0.34-0.58; ITT P=0.168, CI95(%) 0.31-0.53), and endoscopic scores (PP P=0.086, CI95(%) 0.74-0.92; ITT P=0.366, CI95(%) 0.66-0.86) did not show statistical differences. Remission was higher in the VSL#3 group than in the placebo group (47.7% vs. 32.4%; PP P=0.069, CI95(%) 0.36-0.60; ITT P=0.132, CI95(%) 0.33-0.56). Eight patients on VSL#3 (11.2%) and nine patients on placebo (12.3%) reported mild side effects. CONCLUSIONS: VSL#3 supplementation is safe and able to reduce UCDAI scores in patients affected by relapsing mild-to-moderate UC who are under treatment with 5-ASA and/or immunosuppressants. Moreover, VSL#3 improves rectal bleeding and seems to reinduce remission in relapsing UC patients after 8 weeks of treatment, although these parameters do not reach statistical significance.

Efficacy and tolerability of ranitidine bismuth citrate plus amoxycillin and clarithromycin as first- or second-line therapy to cure Helicobacter pylori infection.

BACKGROUND/AIMS: Ranitidine bismuth citrate has recently been introduced for the treatment of H. pylori infection and obtains good eradication rates; however, eradication failures still appear in a considerable proportion of cases. The aim of this study was to compare the efficacy and tolerability of ranitidine bismuth citrate plus amoxycillin and clarithromycin as first- or second-line therapy to cure H. pylori infection. METHODOLOGY: We studied 423 consecutive H. pylori-positive patients. In 210 consecutive patients H. pylori infection was diagnosed for the first time (group A), while 213 consecutive patients were enrolled after failure of a first attempt to eradicate H. pylori (group B). All patients received ranitidine bismuth citrate 400 mg b.d. plus clarithromycin 500 mg b.d. and amoxycillin 1 g b.d. for seven days. H. pylori-status was evaluated by means of histology and rapid urease test at entry and by 13C-urea breath test in all patients one month after treatment. RESULTS: 410/423 patients completed the study (202/210 in group A and 208/213 in group B). Two patients of group A and 1 patient of group B were withdrawn from the study due to poor compliance, 6 group A patients and 4 group B patients were lost to follow-up. In group A, after the end of treatment, 181/202 patients were H. pylori-negative (per-protocol analysis: 89.60% [C.I. 95%: 82-95%]; on intention-to-treat analysis: 86.19% [C.I. 95%; 76-92%]), side-effects occurred in 29 patients (13.80%); they were severe in 2 patients and the patients were withdrawn from the study. In group B, after the end of treatment, 200/208 patients were H. pylori-negative (per-protocol analysis: 95.15% [C.I. 95%; 92-100%], on intention-to-treat analysis: 93.89% [C.I. 95%; 89-98%), side-effects occurred in 11 patients (5.13%); they were slight or mild and did not require discontinuation of the treatment. The results of group B were statistically better than group A, both in eradication rate (P < 0.01) as well as both side-effects provoked (P < 0.01). CONCLUSIONS: Ranitidine bismuth citrate-clarithromycin-amoxycillin is more effective when used as second-line therapy rather than when used as first-line therapy; second, ranitidine bismuth citrate-clarithromycin-amoxycillin shows lower and slighter side-effects when used as second-line therapy rather than when used as first-line therapy; finally, the excellent tolerability of ranitidine bismuth citrate + clarithromycin + amoxycillin influences positively the patients' compliance, both as first- and second-line therapy.

Effect of lactoferrin supplementation on the effectiveness and tolerability of a 7-day quadruple therapy after failure of a first attempt to cure Helicobacter pylori infection.

BACKGROUND: Up to 35% of H. pylori-positive patients remain infected after a first eradication attempt. Lactoferrin, a natural anti-bacterial glycoprotein, seems a promising tool in treating H. pylori infection, but it has never been used in second-line treatment. MATERIAL/METHODS: A prospective, randomized study was conducted on 70 consecutive patients with persistent H. pylori infection after failure of the first standard treatment schedule. All patients were randomly treated with ranitidine bismuth citrate (RBC, 400 mg b.d.), esomeprazole (40 mg/day), amoxycillin (1 g t.d), and tinidazole (500 mg b.d.) without (group A) or with (group B) supplementation of bovine lactoferrin (200 mg b.d). One month after conclusion of therapy, endoscopy was performed in those patients for whom the examination was clinically relevant. The remaining patients were checked by 13C-urea breath test. RESULTS: Sixty-seven patients were fully compliant and completed the study (33, i.e. 94.28%, in group A and 34, 97.14%, in group B). One group A patient (2.85%) was excluded for protocol violation and one group B patient (2.85%) was lost to follow-up. H. pylori eradication was obtained in 31/33 (on intention-to-treat: 88.57%, 95%CI: 87-99%) group A patients and in 33/34 (on intention-to-treat: 94.28%, 95%CI: 86-100%) group B patients (p=ns). 16/68 patients (23.53%) experienced side effects (29.41% in group A and 17.64% in group B, p= 0.05). CONCLUSIONS: Lactoferrin supplementation was found effective in reducing side-effect incidence. Moreover, it seems capable of achieving a slight (and not statistically significant) improvement in eradicating H. pylori when used in second-line treatment.

Monoclonal gammopathy of undetermined significance predisposing to Helicobacter pylori-related gastric mucosa-associated lymphoid tissue lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT)-associated B-cell proliferation may range from benign to malignant, and Helicobacter pylori is the only identified critical antigenic stimulus to the development of gastric MALT. Monoclonal gammopathy of undetermined significance (MGUS) is characterized by B-cell hyper-activation and clonal expansion and is know to predispose to B-cell malignancies. We report a patient with MGUS and H. pylori infection in whom we noted the progression of gastritis to acquired gastric MALT and gastric MALT to MALT lymphoma during a 3-year follow-up.

Low-dose balsalazide plus a high-potency probiotic preparation is more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis.

BACKGROUND: Balsalazide is well tolerated and effective in treating acute ulcerative colitis. VSL#3 is a probiotic cocktail proven to be effective in preventing flare-ups of chronic pouchitis. We compared the efficacy and safety of low-dose balsalazide (2.25 g/day) plus 3 g/day VLS#3 (group A) with medium-dose balsalazide alone (group B) and with mesalazine (group C) in the treatment of mild-to-moderate active ulcerative colitis. MATERIAL/METHODS: Ninety patients (30 per group) were randomly enrolled, with a treatment duration of 8 weeks. Efficacy was assessed by symptoms assessment, endoscopic appearance, and histological evaluation. RESULTS: Balsalazide/VSL#3 was significantly superior to balsalazide alone and to mesalazine in obtaining remission: 24 patients of group A were in remission [per-protocol: 85.71% (C.I.95%: 62-96), on intention-to-treat: 80% (C.I.95%: 59-91)], while 21 group B [per-protocol: 80.77% (C.I. 95%: 51-82), on intention-to-treat: 77% (C.I.95%: 43-81)] and 16 group C patients [per-protocol: 72.73% (C.I. 95%: 30-75), on intention-to-treat: 53.33% (C.I.95%: 42-62)] were in remission (p<0.02). Balsalazide with or without VSL#3 was better tolerated than mesalazine: two group C patients were withdrawn from the study because of severe side-effects; 1 group A (3.33%), 3 group B (10%) and 4 group C (13.33%) patients experienced slight side-effects. The balsalazide/VSL#3 combination was faster in obtaining remission than balsalazide alone or mesalazine (4, 7.5, and 13 days in groups A, B and C, respectively) and also better in improving all parameters evaluated. CONCLUSIONS: Balsalazide/VSL#3 may be a very good choice in the treatment of active mild-to-moderate active ulcerative colitis instead of balsalazide alone or mesalazine.

Effect of Lactobacillus casei supplementation on the effectiveness and tolerability of a new second-line 10-day quadruple therapy after failure of a first attempt to cure Helicobacter pylori infection.

BACKGROUND: Probiotics have never been used as second-line treatment in patients resistant to a first course of anti-H. pylori treatment. MATERIAL/METHODS: 70 consecutive patients with persistent H. pylori infection were enrolled and treated with ranitidine bismuth citrate (RBC) 400 mg b.d, esomeprazole or pantoprazole 40 mg/day, amoxycillin 1 g t.d, tinidazole 500 mg b.d. with (group A) or witlhout (group B) supplementation with 750 mg daily containing 16 billion bacteria Lactobacillus casei subsp. casei DG. Esomeprazole or pantoprazole 40 mg/day was administered for a further 4 weeks in cases of active peptic ulcer or severe gastritis detected at endoscopy. In these cases endoscopy was repeated one month after conclusion of therapy. The remaining patients were checked by 13C-urea breath test. RESULTS: Sixty-six patients completed the study, 34 in group A and 32 in group B. One group A patient (2.85%) was excluded for protocol violation and one group B patient (2.85%) was lost to follow-up. 33/34 group A patients were H. pylori-negative [per-protocol: 97.05%, on intention-to-treat: 94.28%]. 5/34 patients (14.7%) showed side-effects, but all of them completed the treatment. In group B, two patients (5.71%) showed severe side-effects and were withdrawn from the study. 30/32 patients were H. pylori-negative [per-protocol: 93.75%, on intention-to-treat: 85.71% (p = n.s.)]. 11/32 patients (34.37%) showed side-effects, but all of them completed the study (p < 0.05). CONCLUSIONS: This 10-day quadruple therapy obtains a high eradication rate, but probiotic supplementation reduces side-effects and permits a slight improvement in eradicating H. pylori.