Guijarro LG, Mate J, Gisbert JP, Perez-Calle JL, Marín-Jimenez I, Arriaza E, Olleros T, Delgado M, Castillejo MS, Prieto-Merino D, Lara VG, Peña AS. N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: Randomized, placebo-controlled pilot study. World J Gastroenterol 2008; 14(18): 2851-2857 [PMID: 18473409 DOI: 10.3748/wjg.14.2851]
Corresponding Author of This Article
Luis G Guijarro, PhD, Unidad de Toxicología Molecular Hepática, Department de Bioquímica & Biología Molecular, Universidad de Alcalá, E-28871, Alcalá de Henares, Spain. luis.gonzalez@uah.es
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Rapid Communication
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World J Gastroenterol. May 14, 2008; 14(18): 2851-2857 Published online May 14, 2008. doi: 10.3748/wjg.14.2851
N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: Randomized, placebo-controlled pilot study
Luis G Guijarro, Jose Mate, Javier P Gisbert, Jose Luis Perez-Calle, Ignacio Marín-Jimenez, Encarna Arriaza, Tomás Olleros, Mario Delgado, Maria S Castillejo, David Prieto-Merino, Venancio Gonzalez Lara, Amado Salvador Peña
Luis G Guijarro, Mario Delgado, Maria S Castillejo, David Prieto-Merino, Department of Biochemistry and Molecular Biology, CIBERehd, Alcalá University, Alcalá de Henares, Madrid, Spain
Jose Mate, Javier P Gisbert, Gastroenterology Unit, CIBERehd La Princesa University Hospital, Autonomous University, Madrid, Spain
Jose Luis Perez-Calle, Ignacio Marín-Jimenez, Venancio Gonzalez Lara, Gastroenterology Unit, Gregorio Marañón University Hospital, Complutense University, Madrid, Spain
Encarna Arriaza, Tomás Olleros, Group Farmasierra SL., Ctra N-II Km 26.200, San Sebastián de los Reyes, Madrid, Spain
Amado Salvador Peña, Laboratory of Immunogenetics, Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
Author contributions: Guijarro LG designed the study, carried out the statistical analysis and wrote the first draft of the manuscript; Mate J compiled the data patients; Gisbert JP helped write and correct the paper; Perez-Calle JL compiled the data patients; Marín-Jimenez I compiled the data patients; Arriaza E organized patient data; Olleros T organized patient data; Delgado M did ELISA assays; Castillejo MS did ELISA assays and GSH measurement; Prieto-Merino D carried out statistical data; Gonzalez Lara V compiled the data patients; Peña AS helped write, corrected and supervised the organization process.
Correspondence to: Luis G Guijarro, PhD, Unidad de Toxicología Molecular Hepática, Department de Bioquímica & Biología Molecular, Universidad de Alcalá, E-28871, Alcalá de Henares, Spain. luis.gonzalez@uah.es
Telephone: +34-918854865
Fax: +34-918854585
Received: January 31, 2007 Revised: March 23, 2008 Published online: May 14, 2008
Abstract
AIM: To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine (NAC) co-administration with mesalamine in ulcerative colitis (UC) patients.
METHODS: Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine (2.4 g/d) plus N-acetyl-L-cysteine (0.8 g/d) (group A) or mesalamine plus placebo (group B). Patients were monitored using the Modified Truelove-Witts Severity Index (MTWSI). The primary endpoint was clinical remission (MTWSI ≤ 2) at 4 wk. Secondary endpoints were clinical response (defined as a reduction from baseline in the MTWSI of ≥ 2 points) and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment.
RESULTS: Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine (group A) and mesalamine plus placebo (group B) respectively (OR = 1.71; 95% CI: 0.46 to 6.36; P = 0.19; NNT = 7.7). Analysis of variance (ANOVA) of data indicated a significant reduction of MTWSI in group A (P = 0.046) with respect to basal condition without significant changes in the group B (P = 0.735) during treatment. Clinical responses were 66% (group A) vs 44% (group B) after 4 wk of treatment (OR = 2.5; 95% CI: 0.64 to 9.65; P = 0.11; NNT = 4.5). Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION: In group A (oral NAC combined with mesalamine) contrarily to group B (mesalamine alone), the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.
