A pilot study of treatment of active ulcerative colitis with natalizumab, a humanized monoclonal antibody to alpha-4 integrin.

BACKGROUND: Alpha-4 integrins facilitate leucocyte migration across vascular endothelium. AIM: To assess the safety and efficacy of natalizumab (Antegren), a humanized antibody to alpha-4 integrin, in patients with active ulcerative colitis. METHODS: Ten patients with active ulcerative colitis, defined by a Powell-Tuck activity score > 4, received a single 3 mg/kg natalizumab infusion. The primary end-point was the change in Powell-Tuck score at 2 weeks post-infusion. RESULTS: Significant decreases in the median Powell-Tuck score were observed at 2 and 4 weeks post-infusion (7.5 and 6, respectively) compared to the median baseline score (10). Five of 10 patients achieved a good clinical response at 2 weeks and one more patient by 4 weeks, defined by a Powell-Tuck score of < or = 5. Significant improvements in quality of life scores were found at week 4. Rescue medication was required by two (20%), three (30%) and eight (80%) patients by weeks 2, 4 and 8, respectively (median, 34 days; range, 8-43 days). One patient remained in remission at 12 weeks. The median C-reactive protein at 2 weeks (6 mg/L) was lower than that pre-treatment (16 mg/L). CONCLUSIONS: A single 3 mg/kg infusion of natalizumab was well tolerated by ulcerative colitis patients. The positive efficacy demonstrated in this study merits further investigation by randomized, placebo-controlled trials.

Long term management of duodenal ulcer in general practice: how best to use cimetidine?

Two hundred and sixty seven patients with duodenal ulceration were entered into a five year study of two strategies of treatment with cimetidine. Two thirds were treated continuously with 400 mg at bedtime supplemented by temporary increases in dosage if they had symptomatic relapses (group 1), and the remaining third were given intermittent "healing" doses for four to eight weeks if a symptomatic recurrence was judged to have occurred (group 2). Life table analysis showed that the probability of remaining free of clinically important symptoms five years after the start of treatment was 24% (95% confidence interval (CI) 15.5% to 32.6%) in group 1 compared with nil in group 2 (p less than 0.0001). The median values for the longest periods free from relapse for each patient were 108 weeks in group 1 and 32 weeks in group 2, respectively (p less than 0.0001; 95% CI of the median difference 36 to 76). Over the five years 10 patients suffered major complications, two requiring emergency surgery, while a further nine had elective surgery because of the failure of medical treatment. There were no deaths that could be attributed either to ulceration or to treatment with cimetidine. Medical management was therefore very satisfactory for most patients, though those treated continuously with cimetidine suffered considerably less from their ulcer symptoms. As 80% of patients studied relapsed during the two years after a healing course of cimetidine, continuous treatment will benefit many patients treated in general practice.

Hydrochlorothiazide and triamterene with sustained-release oxprenolol in the treatment of hypertension.

A single-blind, three-way Latin square crossover study without wash-out periods was performed in a general practice. Thirty moderately hypertensive patients were studied to compare the antihypertensive effect of 160 mg sustained-release oxprenolol once daily, 25 mg hydrochlorothiazide/50 mg triamterene once daily or a combination of the two preparations once daily, each treatment being given for 1 month. Blood pressure control was significantly better with the combination than with either agent used separately. Pulse rates, as expected, were lower when sustained-release oxprenolol was taken either alone or in the combination. Adverse events led to withdrawal in 1 patient only. Otherwise, all treatments were well tolerated and compliance was excellent. Renal function tests indicated a slight increase in creatinine, urate and urea levels after the treatments which included hydrochlorothiazide compared with oxprenolol alone, although the results were of no clinical significance.

Is sustained-release ibuprofen as effective as piroxicam? A comparison in patients with osteoarthritis.

One hundred and thirty-one patients with osteoarthritis of the knee or hip entered a comparative trial of sustained release (SR) ibuprofen ('Fenbid') and piroxicam ('Feldene'). Paracetamol was provided as 'escape' medication. During the 3 week treatment period the patients assessed pain and stiffness in either the knee or hip as well as general joint pain and stiffness and duration of morning stiffness, overall wellbeing, sleep disturbance and paracetamol consumption. Physicians assessed response to joint manipulation and the function of the joint subjectively. The results were statistically compared with those from a run-in period during which only paracetamol was given. Over the trial period significant improvement was noted in all of the parameters with both treatments. SR ibuprofen was significantly better than piroxicam at reducing morning stiffness. In addition fewer patients taking ibuprofen experienced upper gastrointestinal symptoms, 4% compared to 20% taking piroxicam.

Prolactin responses to cimetidine.

1 An intravenous injection of cimetidine 400 mg to four healthy male subjects resulted in high blood concentrations of cimetidine and a rapid three-fold increase in serum prolactin. 2 This effect was prevented by pretreatment with bromocriptine. 3 No increase in prolactin followed a single oral dose of cimetidine 800 mg administered to a different group of healthy male subjects. The mean peak blood concentration of cimetidine was less than 20% of that achieved with 400 mg i.v. 4 Only isolated reports have been received of gynaecomastia or galactorrhoea occurring during cimetidine treatment. In three of seven cases studied there was associated hyperprolactinaemia. This may be an idiosyncratic response at the lower blood concentration of cimetidine associated with oral therapeutic dose regimens.