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P550 Anti-mycobacterium paratuberculous therapy in Crohn’s disease: outcomes from tertiary IBD referral centres

E. Johnston*1, S. Honap1, B. Al-Hakim1, J. Sanderson1

1Guy's and St. Thomas' Hospitals NHS Foundation Trust, Gastroenterology, London, UK

Background

Mycobacterium avium paratuberculosis (MAP), an obligate intracellular pathogen, has long been proposed as an aetiological factor in Crohn’s disease. Prolonged, combination antibiotic therapy has shown beneficial effect in the induction and maintenance of remission in a small number of studies but was not replicated in an RCT.1 However, the evidence remains conflicting, particularly with criticisms on experimental design and subtherapeutic antibiotic dosing in the latter. We report the outcomes of this therapeutic option in a selected cohort of patients at our institutions.

Methods

A retrospective study was conducted by examining the records of adult patients commenced on anti-MAP therapy (AMT) at both Guy’s and St. Thomas’ Hospitals and London Bridge Hospital, between February 2011 to December 2017. Treatment regimens were slightly varied but standard therapy was clarithromycin 750 mg OD, rifabutin 450 mg OD and clofazimine 100 mg OD. Hospital notes were used to capture demographic data, disease characteristics and therapy details including indications and duration of therapy. Objective measures of response included at least one of; reduction in CRP or faecal calprotectin, improvement in endoscopic or radiological appearances. Statistical analysis was performed using GraphPad Prism.

Results

In total, 62 patients were prescribed AMT over the study period, 21 were excluded due to insufficient outcome data. 21/41 (51%) were male and median age was 28 (range 18–63) at the time of commencing therapy. The cohort had moderate to severe Crohn’s disease with 26 (63%) having stricturing or penetrating disease and 18 (44%) with previous surgery. Thirty-one (76%) had previously received biologic therapy. AMT was commenced in 26 (63%) patients due to failure of conventional therapy, 3 (7%) in patients where conventional therapy was not appropriate and the remaining due to patient preference. AMT was well tolerated with only 5 (12%) patients stopping therapy due to adverse effects. Nineteen patients (46%) demonstrated at least partial benefit, corroborated by objective evidence in 13/19 (68%). Response was not associated with disease phenotype and duration, previous therapy or use of clofazimine. Those patients who responded had a longer duration of therapy (median 24 months compared with 14 months; p = 0.04) than patients who did not respond.

Conclusion

Our study demonstrates that in a cohort of patients in which the majority failed conventional treatment, AMT was well tolerated and a response was seen in 46%. Patients who responded were on AMT a median 24 months which supports the current recommendation of a 24-month duration of treatment. Limitations include a small, heterogenous cohort of patients.

Reference

1. Selby WS, Pavli P, Crotty B, et al. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn’s disease. Gastroenterology 2007;132:2313–9.