Gastroenterology

Gastroenterology

Volume 117, Issue 6, December 1999, Pages 1271-1277
Gastroenterology

Alimentary Tract
Thalidomide therapy for patients with refractory Crohn's disease: An open-label trial,☆☆

https://doi.org/10.1016/S0016-5085(99)70276-3Get rights and content

Abstract

Background & Aims: Inhibition of tumor necrosis factor is a proposed mechanism for the anti-inflammatory properties of thalidomide. We performed an open-label trial of thalidomide in refractory Crohn's disease. Methods: Twenty-two patients with refractory Crohn's disease (Crohn's Disease Activity Index [CDAI] > 200 and/or draining perianal disease) initiated therapy with thalidomide, 200 mg at bedtime (18 patients), or 300 mg at bedtime (4 patients). CDAI and goal interval scores (GIS) were assessed at weeks 0, 4, and 12. Clinical response for patients with luminal disease was defined as reduction in CDAI score of >150 points and for fistula patients was 2 scores of ≥1+ in 3 parameters of the GIS. Clinical remission was defined as a total CDAI < 150 (luminal patients) or ≥2+ for all parameters of the GIS (fistula patients). Results: Nine patients with luminal disease and 13 with fistulas (16 male, 6 female) were enrolled. The median CDAI score at entry was 371 (95–468). Sixteen patients completed 4 weeks of treatment (12 clinical responses, 4 clinical remissions). All 14 patients completing 12 weeks met criteria for clinical response. Nine achieved clinical remission (3 luminal, 6 fistula patients). The median CDAI score was 175 (30–468; P < 0.001 vs. baseline). Conclusions: Thalidomide is efficacious in some patients with refractory Crohn's disease.

GASTROENTEROLOGY 1999;117:1271-1277

Section snippets

Patient selection and study design

This study was conducted under an Investigational New Drug (IND) from the Food and Drug Administration (IND 57,302) at 2 medical centers, the University of Chicago in Chicago, Illinois, and Sunnybrook Hospital in Toronto, Ontario. Patients with steroid-refractory luminal Crohn's disease (Crohn's Disease Activity Index [CDAI] > 200 but unable to taper the equivalent of 15 mg of prednisone/day) or refractory fistulizing Crohn's disease (continuous drainage of perianal fistulas despite therapy

Results

Nineteen patients were initially enrolled at the University of Chicago between May 1998 and November 1998; 1 patient with fistulas withdrew before taking any medication and was not included in subsequent analysis. Four patients were enrolled at Sunnybrook Hospital between 1996 and 1998. In total, 9 were enrolled for luminal disease and 13 for fistulas. There were 6 women and 16 men, with a median age of 39.5 years (range, 23–61 years). The median CDAI score at entry for study patients was 371

Discussion

Thalidomide has previously been shown to be effective in granulomatous and other inflammatory disorders in which TNF has been implicated as an important mediator of inflammation.6, 7, 8, 9, 10, 11, 17 One potential mechanism for these effects is inhibition of TNF-α production.5, 18 In recent trials, thalidomide was efficacious for HIV-associated oral aphthous19 or esophageal ulcers,15, 20 Behçet syndrome,21 and sarcoidosis,22 conditions that share some clinical characteristics with Crohn's

Acknowledgements

The authors thank Diane Sredojevic for administrative assistance and manuscript preparation.

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    • Long-term Outcomes of Thalidomide Therapy for Adults With Refractory Crohn's Disease

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    Address requests for reprints to: Eli D. Ehrenpreis, M.D., University of Chicago Hospitals, 5841 South Maryland Avenue, MC4076, Chicago, Illinois 60637. e-mail: [email protected]; fax: (773) 702-2182.

    ☆☆

    Supported in part by a grant from the Gastrointestinal Research Foundation, Chicago, Illinois, and the University of Chicago's Clinical Research Center.

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