Published online Mar 7, 2019. doi: 10.3748/wjg.v25.i9.1142
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
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.
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.
This systematic review aims to investigate data on the efficacy of conventional therapy for MS-IBD.
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.
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.
High-quality evidence assessing conventional therapy in MS-IBD treatment is scarce, especially for remission maintenance, mucosal healing and fecal calprotectin.
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.