THALIDOMIDE IN CROHN'S DISEASE
Antony R Wettstein, Alan P Meagher. Departments of Gastroenterology and Colorectal Surgery, St Vincent's Hospital, Sydney 2010, Australia. Lancet, Volume 350, Number 9089, 15 November 1997
Thalidomide has been shown to be effective in treating idiopathic oral and oropharyngeal apthous ulceration in HIV-1 positive patients.1 Inhibition of tumour necrosis factor-alpha(TNF-alpha) by thalidomide may be an important mechanism of action.2 TNF-alpha is thought to have an effect in Crohn’s disease,3 and antibodies to TNF- alpha decrease the activity of Crohn’s disease.4,5 We treated a patient with severe recurrent bleeding due to Crohn’s disease with thalidomide.
A 55-year-old woman weighing 39 kg with a 32-year history of Crohn’s disease requiring multiple small bowel and colonic resections for fistulae, abscesses, and strictures resulting in short-bowel syndrome, presented with rectal bleeding and a haemoglobin of 6·6 g/dL. Colonoscopy showed actively bleeding circumferential ulcers at both the left colonic and ileo-colonic anastomoses, and multiple discrete large ulcers in the terminal small bowel. After transfusion, high-dose oral steroids and iron supplements were started, and sulfasalazine was changed to mesalazine. Over the next 6 months, bleeding continued, requiring 12 readmissions to hospital. Azathioprine, intravenous steroids, bowel rest and total parenteral nutrition, metronidazole, and cyclosporin were tried without success. Three follow-up colonoscopic examinations showed no notable change. Intravenous access was becoming difficult, with the need for subclavian catheters for transfusions. Operative treatment was considered though unlikely to be successful.
With informed consent of the patient, thalidomide was started at a dose of 300 mg daily. Visible bleeding diminished over 3 weeks, and has not recurred. Whereas 39 units of blood were required in the 6 months from presentation with bleeding to introduction of thalidomide, no transfusions have been required in the 4 months since. Somnolence has been the only side-effect noted, and after 2 months the dose was decreased to 200 mg daily. The most recent haemoglobin, 4 months after thalidomide was started, was 11·3 g/dL, whilst a colonoscopy at the same time showed resolution of both anastomotic and small bowel ulceration. The dose of thalidomide now has been decreased to 100 mg daily.
While the intensity of Crohn’s disease activity can vary spontaneously,
there appears to be a strong possibility that thalidomide has been helpful
in this patient. A controlled trial of thalidomide in selected patients
with severe treatment-resistant Crohn’s disease is warranted.
THALIDOMIDE EFFECTIVE FOR ESOPHAGEAL ULCERS IN HIV PATIENTS
Atlanta, Georgia, March 20, 1997
Thalidomide appears to be a useful alternative to prednisone for HIV-positive patients with idiopathic esophageal ulcers, according to Dr. Lorraine N. Alexander of Emory University in Atlanta, Georgia, and Dr. C. Mel Wilcox of the University of Alabama in Birmingham.
The researchers prospectively studied 12 HIV-positive subjects with idiopathic esophageal ulcers, two of whom had failed oral corticosteroid therapy. The subjects received thalidomide 200 mg/day orally over a 28-day period.
They found that 11 of the 12 patients had a complete symptomatic response. The results of endoscopy, which was performed in 11 patients, indicated that nine subjects had complete healing of the ulcer, one had partial healing and one patient did not respond. The latter required an increased dose and duration of therapy, and thalidomide was well tolerated with no significant side effects. The investigators then followed the subjects for 20 months, performing endoscopy if esophageal symptoms recurred. Among 14 survivors, 3 patients experienced relapse of esophageal ulcer over the follow-up period, but responded to retreatment with thalidomide (one subject) or corticosteroid therapy (two subjects).
The researchers conclude that thalidomide is a useful alternative to corticosteroids for the treatment of idiopathic esophageal ulcers. Importantly, it also appears to be effective for those patients failing corticosteroids, and may represent first-line therapy for those patients with contraindications to corticosteroids
CCFA page on thalidomide (clinical trial in progress in Chicago)