Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series

Abstract

Background: Crohn's disease (CD) is rising in incidence and has a high morbidity and increased mortality. Current treatment use immunosuppressives but efficacy is suboptimal, and relapse is common. It has been shown that there is an imbalance present in the gut microbiome (dysbiosis) in CD with a possible infective aetiology-Mycobacterium avium subsp. paratuberculosis (MAP) being the most proposed. Antibacterial therapy and Faecal Microbiota Transplantation (FMT) are emerging treatments which can result in clinical and endoscopic remission, if employed correctly. The objective of this study was to report on the treatment and clinical outcomes of patients with CD in prolonged remission.Results: Ten patients were identified to have achieved prolonged remission for 3-23 years (median 8.5 years). Of these, 7/10 took targeted Anti-MAP therapy (AMAT) for a median 36 months and then ceased AMAT treatment. After stopping AMAT five patients underwent Faecal Microbiota Transplantation (FMT) (average four infusions). In 4/7, AMAT was combined with infliximab (mean of six infusions) that was withdrawn within 6 months after fistulae resolution. One patient achieved deep mucosal healing with AMAT alone. Of the 3/10 patients not prescribed AMAT, one had a combination of anti-inflammatory agents and a single antibiotic (metronidazole) followed by FMT. The other two received only FMT for Clostridioides difficile Infection. Conclusions:Prolonged remission has been achieved for 3-23 years with individualised treatments, with the majority using AMAT ± infliximab and FMT. Treatment with antibiotics and/or FMT provides a potential new avenue for treatment of CD. These findings should stimulate thinking, investigations and better therapy against MAP and the dysbiosis of the gut flora, to enable higher rates of prolonged remission.

The role of faecal microbiota transplantation in the treatment of inflammatory bowel disease

“…To date, there have been no powered RCTs of FMT in CD. Clinical remission rates in uncontrolled cohort studies and case series have varied greatly from 0 to 76% [ 24 , 38 , 39 , 40 ]. A meta-analysis of 6 cohort studies (71 patients) determined the pooled proportion of CD patients achieving clinical remission with FMT was 52% (95% CI 31–72%) with significant heterogenicity and publication bias [ 19 • ].…”

Crohn’s strictures open with anti-mycobacterial antibiotic therapy: A retrospective review

“…This points to CD being a transmural, mycobacterial-driven infection and inflammation, a concept already supported by other evidence[ 42 - 44 ]. Given that AMAT induces remission in CD significantly better than placebo, independently of other treatment, across multiple age ranges, and has produced prolonged disappearance of disease, our review supports the parallel between the majority of TB and CD strictures; in that both are mycobacterial infections which improve using antibiotics[ 24 - 26 , 45 , 46 ]. However, definitive conclusions of this relationship should be tempered until AMAT has demonstrated its benefit in CD with further supporting evidence[ 28 ].…”

“…Additionally, even within a pediatric cohort, AMAT appears to confer a benefit yielding a robust clinical and endoscopic remission rate[ 25 ]. In a subset of CD patients given AMAT the disease can completely disappear for more than three years without further therapy, as has previously been demonstrated with duodenal ulcer disease[ 26 , 27 ]. It should be noted that in an up to date systematic review of AMAT, the authors conclude it may provide a benefit over placebo, but higher quality evidence is needed before it can be indicated for CD[ 28 ].…”

Inflammatory Bowel Diseases: Host-Microbial-Environmental Interactions in Dysbiosis

“…However, since dysbiosis does not lead to IBD in all individuals it is likely that host factors that predispose to the development of IBD play a role in onset. These may facilitate an expansion of pathobionts in the intestine, which could in turn lead to metabolic changes in the gut that limit the viability or competitiveness of potentially beneficial bacteria [ 206 , 207 , 208 , 209 , 210 ].…”