Phosphatidylcholine for Steroid-Refractory Chronic Ulcerative Colitis

A Randomized Trial

6 November 2007 | Volume 147 Issue 9 | Pages 603-610

Background: Although long-term steroid treatment is discouraged in ulcerative colitis, alternatives are lacking when therapy with immunosuppressant drugs fails. An insufficient level of phosphatidylcholine in colonic mucus is a possible pathogenetic factor for ulcerative colitis.

Objective: To see whether steroid withdrawal is easier with retarded-release phosphatidylcholine or placebo in adults with chronic steroid-refractory ulcerative colitis.

Design: Randomized, double-blind, placebo-controlled trial conducted from March 2003 to January 2006.

Setting: University Hospital Heidelberg, a referral center for inflammatory bowel disease.

Patients: 60 patients with chronic steroid-refractory ulcerative colitis and high clinical and endoscopic disease activity indexes (score 5).

Intervention: Phosphatidylcholine or cellulose placebo was ingested 4 times daily for 12 weeks for a total dosage of 2 g/d. The follow-up rate was 97%.

Measurements: The number of patients achieving complete steroid withdrawal and either a low clinical activity index (3) or improvement in the clinical activity index of 50% or more.

Results: The primary end point was achieved in 15 of 30 (50%) phosphatidylcholine recipients and in 3 of 30 (10%) placebo recipients (difference, 40% [95% CI, 19% to 61%]; P = 0.002). Twenty-four phosphatidylcholine recipients (80%) and 3 (10%) placebo recipients discontinued steroid therapy without disease exacerbation (difference, 70% [CI, 52% to 88%]; P <0.001). Mild bloating was a common adverse event.

Limitations: The sample size was small, and the study was of short duration.

Conclusion: Phosphatidylcholine reduced corticosteroid dependence more than placebo in patients with chronic steroid-refractory ulcerative colitis. The next step is long-term trials to evaluate the sustainability of steroid withdrawal in these patients.

ClinicalTrials.gov registration number: NCT00259545.

Editors' Notes Context Experts recommend immunosuppressant drugs, rather than long-term steroid therapy, for chronic active ulcerative colitis. Few options remain when immunosuppressant drugs fail or cause intolerable side effects. Contribution In this double-blind trial, 60 adults with chronic steroid-refractory ulcerative colitis in whom immunosuppressant drugs had failed or were poorly tolerated were randomly assigned to receive phosphatidylcholine or placebo for 12 weeks. More phosphatidylcholine recipients improved and achieved steroid withdrawal than placebo recipients (15 of 30 vs. 3 of 30, respectively). More patients reported bloating with phosphatidylcholine than placebo (11 vs. 6). Caution The study had a small sample size and was of short duration. Implication We need larger, long-term trials of phosphatidylcholine as a treatment for ulcerative colitis. —The Editors

 

Author and Article Information

From University Hospital Heidelberg, Heidelberg, Germany.

Acknowledgment: The authors thank Susanne Schäfer for statistical analysis; Annika Braun, MD, and Alexandra Zahn, MD, for assistance in patient management; and Heather Karner, MA, for proofreading and editing services. They also thank Verena Schmieg and Anja Hanemann for assistance in assessing the follow-up data and Daniela Kautz and Anja Hanemann for assisting in the data management and graph generation.

Grant Support: By the Dietmar-Hopp Foundation (Dr. Stremmel).

Potential Financial Conflicts of Interest: Grants received: W. Stremmel (Dietmar-Hopp Foundation). Patents received: W. Stremmel (for retarded-release phosphatidylcholine as a mucoprotective agent for the large intestine.)

Reproducible Research Statement: The protocol (in German, with an English-language synopsis), data set, and statistical code are available to interested readers by contacting Dr. Stremmel (e-mail, wolfgang.stremmel{at}med.uni-heidelberg.de).

Requests for Single Reprints: Wolfgang Stremmel, MD, Department of Gastroenterology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany; e-mail, wolfgang.stremmel{at}med.uni-heidelberg.de.

Current Author Addresses: Drs. Stremmel, Ehehalt, and Karner: Department of Gastroenterology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.

Dr. Autschbach: Pathological Institute, University Hospital Heidelberg, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.

Author Contributions: Conception and design: W. Stremmel, M. Karner.

Analysis and interpretation of the data: W. Stremmel, R. Ehehalt, M. Karner.

Drafting of the article: W. Stremmel, M. Karner.

Critical revision of the article for important intellectual content: W. Stremmel, M. Karner.

Final approval of the article: W. Stremmel, R. Ehehalt, F. Autschbach, M. Karner.

Provision of study materials or patients: W. Stremmel, F. Autschbach, M. Karner.

Statistical expertise: W. Stremmel, M. Karner.

Obtaining of funding: W. Stremmel.

Administrative, technical, or logistic support: W. Stremmel, R. Ehehalt, M. Karner.

Collection and assembly of data: W. Stremmel, R. Ehehalt, F. Autschbach, M. Karner.