Phosphatidylcholine for Steroid-Refractory Chronic Ulcerative Colitis

Phosphatidylcholine for Steroid-Refractory Chronic Ulcerative Colitis

A Randomized Trial

From University Hospital Heidelberg, Heidelberg, Germany.

Abstract

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.

Article and Author Information

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.