Targeted Combination Antibiotic Therapy Induces Remission in Treatment-Naïve Crohn’s Disease: A Case Series

Agrawal, Gaurav; Clancy, Annabel; Sharma, Rijata; Huynh, Roy; Ramrakha, Sanjay; Borody, Thomas J.

doi:10.3390/microorganisms8030371

Cited by 19 publications

(14 citation statements)

References 46 publications

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“…Though a caveat to this is that they may lead to resistance of MAP, where it resides in tissues [40]. A problem that we have observed in the response using AMAT in patients with a history of biologic use compared to 'treatment-naïve' patients [41].…”

Section: Discussionmentioning

confidence: 90%

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

et al. 2020

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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 In 4/7, AMAT was combined with infliximab (mean of six infusions) that was withdrawn within 6 months after fistulae resolution.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.

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Section: Discussionmentioning

confidence: 90%

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

et al. 2020

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“…Hence, one postulation is that the extent of previous immunosuppressive therapy may predict a longer duration to achieve endoscopic remission under AMAT due to the development of resistant forms of MAP in such patients. Certainly, a recent published report by our group supports this notion, in which eight treatment naïve patients experienced significant rates of both clinical and endoscopic remission at 6 weeks and 12 months respectively [31].…”

Section: Discussionmentioning

confidence: 53%

Anti-Mycobacterial Antibiotic Therapy Induces Remission in Active Paediatric Crohn’s Disease

et al. 2020

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Crohn’s disease is increasing in incidence and prevalence in younger people and is of a particularly aggressive nature. One emerging treatment targets Mycobacterium avium paratuberculosis (MAP), an organism implicated in the causation of Crohn’s disease. This study reviewed a cohort of paediatric patients with active Crohn’s disease treated with Anti-Mycobacterial Antibiotic Therapy (AMAT). Sixteen paediatric patients, the majority of whom had failed conventional immunosuppressive therapy, were treated with AMAT. Endoscopic remission was scored using the Simple Endoscopic Score for Crohn’s Disease and clinical remission was assessed using the Weighted Paediatric Crohn’s Disease Activity Index (wPCDAI). Inflammatory blood markers were also routinely recorded. Patients were followed up clinically and endoscopically during treatment after an average of two months (range 1–6) and 17 months (range 2–49), respectively. A significant reduction in both scores assessing clinical improvement (p < 0.001) and mucosal healing (p < 0.0078) was observed at these timepoints; 47% of patients had achieved clinical remission and 63% endoscopic remission. Haemoglobin and serum inflammatory markers normalised for more than 50% of the cohort by six months of treatment. No adverse effects were reported throughout treatment. This is the first report of Anti-Mycobacterial Antibiotic Therapy offering a safe and efficacious therapy for paediatric patients with Crohn’s disease. Further larger randomised studies are required in order to validate these findings.

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“…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 ].…”

Section: Discussionmentioning

confidence: 60%

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

Collyer¹,

Clancy²,

Agrawal³

et al. 2020

WJGE

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BACKGROUND Medical therapy for strictures is limited and first-line treatment consists of endoscopic balloon dilatation, strictureplasty or surgical resection. Mycobacterium tuberculosis , Helicobacter pylori and Streptococcus can all cause stenosis, for which antibiotic treatment achieves stricture resolution. Mycobacterium avium ssp. paratuberculosis is a suspected causative agent in Crohn’s disease (CD). Thus, specialized antimicrobial treatment, in particular, anti-mycobacterial antibiotic therapy (AMAT) has been proposed as a potential treatment option. To our knowledge, the opening of CD strictures has not been recorded using any form of antibiotic therapy. We hypothesized that AMAT would resolve strictures in patients with CD. AIM To investigate the effect and outcomes of AMAT in a cohort of CD patients with an ileal stricture. METHODS A single center, retrospective, medical record case review was conducted on an observational cohort of patients with CD who had an ileal stricture on colonoscopy and were treated with AMAT. Forty patients meeting the inclusion criteria were identified from the internal medical database. Thirty (75%) patients had follow-up colonoscopy and clinical data available. The AMAT regimen was prescribed after the initial colonoscopy for a duration of at least six months until follow-up colonoscopy with the attending gastroenterologist. Patient demographics, symptoms, colonoscopy reports, inflammatory serum markers and concurrent medications were recorded at pre-treatment and follow-up between January 1995 and June 2018. RESULTS Of the patients that returned for follow-up after > 24 mo of AMAT, twenty (67%) had complete resolution (CR) of their ileal strictures, three (10%) had partial resolution and seven (23%) had no resolution. Irrespective of stricture outcome, 21 patients (70%) demonstrated clinical response to AMAT and there was a statistically significant reduction in inflammatory serum markers C-reactive protein ( P < 0.0001) and erythrocyte sedimentation rate ( P = 0.04) from pre-treatment to follow-up. It was observed that 11 (37%) patients experienced side effects, but no serious adverse effects were attributable to AMAT. At follow-up there were 26 (87%) patients on concomitant medication for CD and a statistically significant association between CR and AMAT with a concomitant immunomodulator ( P = 0.02). CONCLUSION This study demonstrated a high rate of stricture resolution (67%) similar to that seen in tuberculosis strictures (70%), suggesting a shared mycobacterial origin of strictures, and perhaps disease.

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Targeted Combination Antibiotic Therapy Induces Remission in Treatment-Naïve Crohn’s Disease: A Case Series

Cited by 19 publications

References 46 publications

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

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

Anti-Mycobacterial Antibiotic Therapy Induces Remission in Active Paediatric Crohn’s Disease

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

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