Systematic Reviews
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2019; 25(9): 1142-1157
Published online Mar 7, 2019. doi: 10.3748/wjg.v25.i9.1142
Conventional therapy for moderate to severe inflammatory bowel disease: A systematic literature review
Adérson Omar Mourão Cintra Damião, Matheus Freitas Cardoso de Azevedo, Alexandre de Sousa Carlos, Marcela Yumi Wada, Taciana Valéria Marcolino Silva, Flávio de Castro Feitosa
Adérson Omar Mourão Cintra Damião, Matheus Freitas Cardoso de Azevedo, Alexandre de Sousa Carlos, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo 05403-000, Brazil
Marcela Yumi Wada, Taciana Valéria Marcolino Silva, Flávio de Castro Feitosa, Department of Medical Affairs, Takeda Pharmaceuticals, São Paulo 04709-011, Brazil
Author contributions: Damião AOMC, Azevedo MFC, Carlos AS, Wada MY, Silva TVM, and Feitosa FC contributed to the analysis and interpretation of data; critically revised the manuscript for important intellectual content; granted final approval of the version to be published; and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Conflict-of-interest statement: Adérson Omar Mourão Cintra Damião has been a speaker for Takeda, Abbvie, and Janssen; has been an advisory board member for Takeda; and has received conference grants from Janssen, Takeda and Abbvie. Matheus Freitas Cardoso de Azevedo and Alexandre de Sousa Carlos have received research grants from Takeda, Janssen, and Abbvie. Marcela Yumi Wada, Taciana Valéria Marcolino Silva and Flávio de Castro Feitosa work at Takeda Pharmaceuticals, Brazil.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Flávio de Castro Feitosa, MSc, PhD, Doctor, Department of Medical Affairs, Takeda Pharmaceuticals, Rua Estilo Barroco, 721, São Paulo 04709-011, Brazil.
Telephone: +55-71-97295355 Fax: +55-11-51810081
Received: December 19, 2018
Peer-review started: December 21, 2018
First decision: January 6, 2019
Revised: January 28, 2019
Accepted: February 15, 2019
Article in press: February 15, 2019
Published online: March 7, 2019
Research background

Inflammatory bowel disease (IBD) frequently present a lifelong relapsing and remitting course with negative impact on health and quality of life, besides long-term sequelae. IBD main treatment goal is the achievement and maintenance of disease remission. Conventional therapies are indicated for patients with moderate to severe disease, despite the advent of biological drugs. Some relevant outcomes, such as clinical remission and endoscopic remission has been correlated with surgeries and hospitalizations reduction.

Research motivation

Conventional therapy continues to be used in moderate to severe IBD (MS-IBD) especially in countries where biologics are not covered by insurance. Thus, extensive knowledge on the efficacy and safety of conventional therapy is necessary.

Research objectives

This systematic review aims to investigate data on the efficacy of conventional therapy for MS-IBD.

Research methods

A systematic review was conducted through the Cochrane Collaboration, MEDLINE, and LILACS databases searching for studies concerning conventional therapy in adult patients with MS-IBD, including Crohn’s disease (CD) and ulcerative colitis (UC). Corticosteroids (prednisone, hydrocortisone, budesonide, prednisolone, dexamethasone), 5-aminosalicylic acid (5-ASA) derivatives (mesalazine and sulfasalazine) and immunosuppressants [azathioprine (AZA), methotrexate (MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine (6-MP)] were considered conventional therapy. Primary outcome measures were clinical remission (induction or maintenance), clinical response and mucosal healing.

Research results

For induction of clinical remission, AZA and 6-MP showed no advantage over placebo, MTX or 5-ASA in CD; MTX showed no statistically significant difference versus placebo, 6-MP, or 5-ASA in UC; tacrolimus was superior to placebo for UC in two meta-analyses. One meta-analysis evaluated clinical remission maintenance, showing no statistically significant difference between MTX and placebo, 5-ASA, or 6-MP in UC. AZA and 6-MP had no advantage over placebo in induction of clinical response in CD. Three meta-analyses showed the superiority of tacrolimus versus placebo for induction of clinical response in UC. The clinical response rates for cyclosporine were 41.7% in randomized controlled trials (RCTs) and 55.4% in non-RCTs for UC. For induction of mucosal healing, one meta-analysis showed a favorable rate with tacrolimus versus placebo for UC. For secondary outcomes, no meta-analyses specifically evaluated fecal calprotectin, hospitalization or death. Two meta-analyses were retrieved evaluating colectomy rates for tacrolimus and cyclosporine in UC. Most of the twenty individual studies retrieved contained a low or very low quality of evidence.

Research conclusions

High-quality evidence assessing conventional therapy in MS-IBD treatment is scarce, especially for remission maintenance, mucosal healing and fecal calprotectin.

Research perspectives

From this systematic review, it could be seen, that further studies with high quality and real-world evidence are needed to prove the effectiveness of conventional therapy in MS-IBD.