Achieving Mucosal Healing in Crohn's Disease and Ulcerative Colitis

March 23, 2017
Amy Reyes

The gold standard for treating Crohn's disease and ulcerative colitis may lie in anti-TNF and anti-integrins therapy, researchers report this week.

Anti-TNF therapy and anti-integrins appear to be the most effective treatment for achieving mucosal healing in Crohn's disease (CD) and ulcerative colitis (UC), a scientific review shows.

Reporting in the March 22 issue of Alimentary Pharmacology and Therapeutics, researchers from Massachusetts General Hospital in Boston, conducted a systematic review and meta-analysis of 12 randomized controlled trials that examined the effectiveness of immunosuppressives, anti-tumor necrosis factor a (anti-TNF) or anti-integrin monoclonal antibody therapy in treating moderate-to-severe Crohn’s disease and ulcerative colitis.

Inflammatory bowel disease (IBD) status was once predominately measured by the severity of symptoms, but this correlated poorly with the presence of endoscopic inflammation so treatment has since shifted to mucosal healing. Long-term studies show that this approach works. Patients who experience mucosal healing have better long-term outcomes, a lower risk of surgery, fewer hospitalizations and use systemic corticosteroids less frequently.

So instead of treatment that focuses on relieving symptoms associated with inflammatory bowel disease, mucosal healing is generally accepted as the preferred endpoint of treatment.

“While symptoms are important determinants of health-related quality of life in IBD, endoscopic severity of inflammation may be a stronger indicator of ongoing bowel damage and need for surgery,” the researchers wrote.

But few studies have incorporated mucosal healing as an endpoint of treatment and as such, there is little information about which therapies work best for achieving this endpoint, the researchers wrote. In this review, researchers found that “anti-TNF biologics are effective in inducing and maintaining mucosal healing in Crohn’s disease and ulcerative colitis while anti-integrin therapies are effective in inducing and maintaining mucosal healing in ulcerative colitis.”

A Norwegian study found that ulcerative colitis patients who experienced a degree of mucosal healing were less likely to undergo a colectomy. They also experienced less inflammation at five years. Crohn’s disease patients in the same study requires fewer corticosteroid treatments.

A study of 214 Crohn’s disease patients treated with infliximab, Schnitzler et al. showed that long-term follow-up surgery rates were half as common as surgery rates for patients who did not experience mucosal healing. Most of the data pointed to the short-term superiority of infliximab over adalimumab in ulcerative colitis, which may be due to intravenous dosing of infliximab.

In summary:

-  For Crohn’s disease, anti-TNF therapy was found to be more effective than placebo in mucosal healing (28% vs.1%, odds ratio 19.71, 95% confidence interval 3.51–110.84).

-  In ulcerative colitis, anti-TNFs and anti-integrins were found to be more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). A network analysis showed that infliximab was superior to adalimumab therapy infliximab (OR 0.45, 95% credible interval (CrI) 0.25–0.82) for ulcerative colitis as was combination therapy with infliximab and azathioprine (OR 0.32, 95% CrI 0.12–0.84), with a trend towards superiority over golimumab. “Combination therapy also demonstrated a trend towards superiority over vedolizumab suggesting that inpatients, particularly in those with severe ulcerative colitis where early induction of mucosal healing is essential, a strategy combining infliximab and azathioprine may be the preferred strategy,” the researchers wrote.

The researchers highlighted a few limitations such as the limited number of clinical trials, some of which were small with no direct head-to-head comparison and wide confidence intervals. In addition, some of the studies defined mucosal healing differently ranging from a Mayo endoscopic sub-score of zero to one.

“There is an important and urgent need for data demonstrating efficacy of all approved agents in achieving mucosal healing to truly inform comparative effectiveness,” the researchers wrote. “While indirect treatment comparisons are informative, they do not supplant the need for direct head-to-head studies to truly inform patient care and guide therapeutic choices to achieve better outcomes.”

 

References:

A Cholapranee, GS Hazlewood, GG Kaplan, L Peyrin-Biroulet, AN Ananthakrishnan. "Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn’s disease and ulcerative colitis controlled trials," Alimentary Pharmacology and Therapeutics. March 22, 2017.  DOI: 10.1111/apt.14030