T. Ranzi

A Placebo-Controlled, Double-Blind, Randomized Trial of Cyclosporine Therapy in Active Chronic Crohn's Disease

We randomly assigned 71 patients with active chronic Crohns disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine (5 to 7.5 mg per kilogram of body weight per day) or placebo for three months. Disease activity was assessed on a clinical grading scale without knowledge of the treatment given. At the end of the treatment period, 22 of the 37 cyclosporine-treated patients (59 percent) had improvement, as compared with 11 of the 34 placebo-treated patients (32 percent) (P = 0.032). During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohns Disease Activity Index (P = 0.00012). The effect of treatment became evident after two weeks. In the subsequent three months, during which the patients were gradually withdrawn from treatment, the improvement continued in 14 of the 37 patients (38 percent) in the cyclosporine group and in 5 of the 34 (15 percent) in the placebo group (P = 0.034). No serious adverse events were observed. We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohns disease and resistance to or intolerance of corticosteroids.

Final Report on a Placebo-Controlled, Double-Blind, Randomized, Multicentre Trial of Cyclosporin Treatment in Active Chronic Crohn's Disease

In a previous report we published the immediate results of a 3-month placebo-controlled trial (n = 34) showing that cyclosporin (n = 37) has a beneficial therapeutic effect in active chronic Crohns disease. Here we report on the final outcome of the patients. During the 3-month tapering-off period eight initially improved patients (36%) in the cyclosporin group worsened, as did six (55%) in the placebo group. The therapeutic gain of cyclosporin treatment was consistently significant during this period. It ranged from 22% to 25% (95% confidence limits, 2-46%). An outcome ranking showed that 7 patients of the cyclosporin group (19%) were substantially improved, 7 (19%) moderately improved, and 23 (62%) not improved after the tapering off. In contrast, no significant differences were seen during the 6-month follow-up period. Four patients of the cyclosporin group (11%) were substantially improved, 3 (8%) moderately improved, and 30 (81%) not improved at final follow-up. Significant interactions between cyclosporin and prednisolone treatment were demonstrated both at the end of the initial treatment period and at the end of the tapering-off period. We conclude that a short course of cyclosporin treatment does not result in long-term improvement in active chronic Crohns disease.

Mesalazine (5-Aminosalicylic Acid) Suppositories in the Treatment of Ulcerative Proctitis or Distal Proctosigmoiditis: A Randomized Controlled Trial

A multicentre double-blind study was conducted to evaluate the efficacy and tolerability of 1 g or 1.5 g mesalazine daily compared with placebo in 94 patients with mild to moderate distal proctosigmoiditis (less than 20 cm). The study end point was the determination of clinical, endoscopic, and histologic remission rates at 4 weeks. Eleven patients, nine receiving placebo and two receiving 1.5 g mesalazine, withdrew during trial, mostly because of worsening of symptoms. At 4 weeks clinical remission was achieved in 7 of 31 (39%) patients with placebo, in 22 of 32 (69%) patients in the 1 g mesalazine group, and 23 of 31 (74%) patients in the 1.5 g mesalazine group. No serious clinical or biochemical side effect of treatment was reported. Mesalazine suppositories are safe, well tolerated, and very effective in patients with active distal proctosigmoiditis: 500 mg twice daily appears a suitable dose regimen.

Controlled trial of oral 5‐aminosalicylic acid for the prevention of early relapse in Crohn's disease

Recent data indicate that 5‐aminosalicylic acid (5‐ASA) is most effective in preventing relapse of Crohns disease in patients with a short duration of remission before enrolment.

Comparative trial of methylprednisolone and budesonide enemas in active distal ulcerative colitis

Objective To compare the clinical effects of budesonide enema 2mg/100ml and methylprednisolone hemisuccinate (MP) enema 20mg/100ml once daily in active distal ulcerative colitis. Design Patients with mild or moderate distal ulcerative colitis (n = 88), which did not extend beyond the splenic flexure, were enrolled in a multicentre randomized investigator blind study comprising a blind treatment period of 4 weeks followed by a 4-week open phase with the same budesonide dose in patients with partial remission. Patients were assessed at 2, 4 and 8 weeks. Results At 4 weeks, 39% of patients on budesonide and 36% on MP were considered to be in clinical remission; budesonide was more effective in patients with moderate disease at entry (36 versus 29%). On sigmoidoscopy, no differences in the porportion of patients with no or only mild signs of mucosal inflammation were observed between budesonide and MP (43 versus 46%, respectively). No significant differences were observed in the histology scores. Of the 37 patients receiving budesonide for a further 4 weeks, 65% achieved symptomatic remission and 47% showed mucosal healing or substantial improvement on endoscopy at 8 weeks. Plasma cortisol levels fell significantly (P < 0.01) after 4 weeks in patients on MP, while only a slight change was observed in those on budesonide. After 8 weeks, plasma cortisol levels were unchanged in patients continuing on budesonide whereas in those switched from MP to budesonide, they approached the baseline value. No drug-related adverse experiences were observed. Conclusions Budesonide enema seems to be as effective as MP enema in the topical treatment of distal ulcerative colitis but unlike conventional steroids, it causes minimal or no adrenal supression.

Bone mineral density and body composition in ulcerative colitis: A six-year follow-up

Abstract: Reduced bone mineral density (BMD) has been reported in ulcerative colitis (UC), but there are no data concerning body composition (fat and lean mass) in such patients. We used whole body dual-energy X-ray absorptiometry (Hologic QDR 1000W) at baseline and after 6 years of follow-up to study bone density, and fat and lean mass in 43 outpatients with mild UC (21 men, mean age 36 years, range 21–57 years, and 22 women, mean age 35 years, range 23–45 years at baseline; disease extent: 2 proctitis, 18 proctosigmoiditis, 8 left colitis, 5 substantial colitis, 10 pancolitis; mean disease duration 8 years, range 2–18 years; no hospitalization; few relapses during the follow-up) and 111 healthy volunteers matched by sex, age and body mass index. There were 5 drop-outs. We observed no significant difference in BMD, or fat and lean mass between the male patients and controls at baseline or after 6 years. The total lean mass (Z-score =−3.2, p=0.001) and trunk lean mass (Z-score =−2.01, p=0.03) of the female patients were lower than those of the controls at baseline, whereas their limb lean mass was higher at both the beginning and the end of the study (Z-score = 2.14, p=0.03; Z-score = 2.8, p=0.004, respectively). At baseline there was a significant negative correlation between lifetime steroid intake (enteral and parenteral) and lumbar spine BMD, obtained as whole body subregion (r=−0.53, p=0.0006). After 6 years there was a significant negative correlation in women between whole body and lumbar spine BMD and both steroid intake (r=−0.53, p=0.01; and r=−0.62, p=0.003) and the number of relapses (r=−0.49, p=0.02; and r=−0.44, p=0.05). Mild UC thus does not represent a risk factor for osteopenia per se. The differences in lean mass between the female patients and controls do not seem to be clinically relevant.

Bone mineral density and body composition in patients with ulcerative colitis

Abstract OBJECTIVE: Reduced bone mineral density (BMD) has been reported in ulcerative colitis (UC) patients, but body composition (fat and lean mass) has never been concomitantly studied. We sought to investigate BMD and body composition in a group of UC outpatients with the following characteristics: age 18–60 yr (men) and 18–45 yr (women); no intestinal resection; no immunosuppressive treatment; and regular menstruation. METHODS: Whole body and subregional BMD and body composition in 43 UC patients (21 men, 22 women; male mean age, 36.5 [21–57] yr; female mean age, 35.3 [23–45] yr) and 121 healthy volunteers were studied by means of dual X-ray photon absorptiometry. RESULTS: There were no differences in total and subregional BMD, or fat and lean mass between the patients and controls, except that the total and trunk lean mass of the UC women was lower than that in the normal controls. No correlation was found between lifetime steroid intake and BMD. CONCLUSIONS: UC outpatients do not differ from normal subjects in terms of BMD and fat mass. Mild and moderate UC does not represent a risk factor for osteopenia.

Successful treatment of genital and oral ulceration in Behcet's disease with topical 5-aminosalicylic acid (5-ASA)

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Topical treatment of active distal ulcerative colitis with beclomethasone dipropionate

Abstract Forty patients with mild or moderately active distal ulcerative colitis were treated for 6 weeks with daily enemas containing beclomethasone dipropionate (BDP) 3 mg or hydrocortisone hemisuccinate (HHS) 100 mg. Each treatment group consisted of 20 patients who were comparable in age, sex, duration of disease, clinical activity, endoscopic scores, and rectal biopsy. Rectoscopy was performed and clinical scores were determined before and after 3 and 6 weeks of treatment; routine blood tests were done at the start and end of the study. Five patients in the BDP group and 3 patients in the HHS group did not respond to therapy. Clinical and endoscopic remission was obtained in 9 patients treated with BDP and in 10 patients given HHS; improvement was noted in 6 patients in the BDP group and in 7 patients in the HHS group. No differences in clinical and endoscopic scores were found between the two treatment groups. Mild moon face developed in two patients receiving HHS. The similar clinical and endoscopic improvement obtained in patients treated with BDP and HHS enemas and the absence of side effects with BDP suggest that topical BDP is a valid alternative in the treatment of active distal ulcerative colitis.