Faecal microbiota transplant for recurrent Clostridioides difficile infection

3.1 The EAC did a systematic review to identify randomised controlled trials (RCTs) comparing faecal microbiota transplant (FMT), by any route of delivery, with NICE-recommended comparators, to treat a Clostridioides difficile infection in people who have had at least 2 previous episodes. It identified and assessed 5 eligible RCTs including 274 adults in total. These trials compared FMT, given via different routes of administration and with a preceding course of antibiotics, with antibiotic treatment. For full details of the clinical evidence, see section 3 of the assessment report.

3.2 FMT (with pretreatment antibiotics) was significantly better at resolving a C. difficile infection than:

3.3 Three trials found lower C. difficile infection recurrence in the FMT group (range 6% to 10%) compared with the antibiotic group (vancomycin range 62% to 69%, fidaxomicin 46%; Cammarota et al. 2015, Hvas et al. 2019 and van Nood et al. 2013). Hota et al. (2017) reported comparable C. difficile infection recurrence after FMT by enema (56.2%) and VTP (41.7%). However, none of the trials reported statistical significance.

3.4 Short-term gastrointestinal side effects were reported in 4 RCTs (Cammarota et al. 2015, Hota et al. 2017, Hvas et al. 2019 and van Nood et al. 2013). The most common effects included diarrhoea, bloating, abdominal pain or cramps. These symptoms lasted (when reported) between 3 hours (van Nood et al. 2013) and 12 hours (Cammarota et al. 2015), or were described as 'transient' (Hvas et al. 2019).

3.5 The included studies had relatively small sample sizes, with a median of 39 and a range of 27 (Rode et al. 2021) to 64 adults (Hvas et al. 2019). This was partly because 4 of the trials stopped early; only 1 completed after recruiting the target number of people (Hvas et al. 2019). The evidence is also limited by not being done in the UK and the trial populations having fewer comorbidities and a lower chance of being hospitalised than the eligible UK population.

3.6 The included studies used different FMT administration routes:

3.7 The EAC did a systematic review to find economic evaluations comparing FMT, by any route of delivery, with NICE-recommended comparators, to treat a C. difficile infection in people who have had at least 2 previous episodes. It assessed 8 economic evaluation studies relevant to the decision problem. Abdali et al. (2020) was a UK-based cost–utility analysis comparing 4 treatments for recurrent C. difficile infection (FMT via NGT, FMT via colonoscopy, oral fidaxomicin, and oral vancomycin). The analysis used a Markov model with 4 health states (relapsed, recovered, recurrent C. difficile infection and dead) and had a cycle length of 2 months and time horizon of 1 year. The analysis found that fidaxomicin and vancomycin were dominated by FMT via NGT and FMT via colonoscopy (that is, FMT was cost saving and more effective).

For full details of the cost evidence, see section 4 of the assessment report and the assessment report appendix.

3.8 The EAC created a cohort Markov model that included adults with recurrent C. difficile infection who have had 2 or more previous episodes. It had a time horizon of 6 months and cycle length of 2 months. The model included 4 routes of FMT administration (colonoscopy, enema, NDT and oral capsules) and 3 antibiotic comparators (vancomycin, fidaxomicin and VTP). It had 4 health states:

3.9 The quality of the clinical evidence leads to uncertainty in the clinical parameters used in the economic model. No eligible RCTs were identified comparing FMT oral capsules with antibiotics in people with 2 or more previous episodes of C. difficile infection. However, because 2 studies found oral capsules were comparable to FMT colonoscopy (Kao et al. 2017, Ramai et al. 2020) the EAC assumed the transition probabilities to be the same. FMT via NGT and flexible sigmoidoscopy were excluded from the economic model because of a lack of RCT-level data from the clinical evidence review.

3.10 The economic model used the following clinical assumptions:

3.11 The EAC's base case analysis found that all 4 routes of FMT were associated with increased health benefits and reduced costs against all 3 antibiotic comparators, with savings ranging from £3,369 (FMT enema compared with VTP) to £13,134 (FMT oral capsule compared with vancomycin). Health benefits ranged from a quality-adjusted life year (QALY) gain of 0.17 (FMT enema compared with VTP) to 0.66 (FMT via NDT compared with vancomycin).

3.12 The EAC identified a meta-analysis by Ramai et al. (2020), which suggested an overall cure rate of 78.1% when FMT is given via NGT. The cost of delivering FMT via NGT is estimated to be £740 (Abdali et al. 2020). Because the cure rate is estimated to be higher for FMT via NGT than via enema, and costs less, FMT via NGT is likely to be cost saving for recurrent C. difficile infections, against all 3 comparators considered.

3.13 The EAC did deterministic and probabilistic sensitivity analyses, and scenario analyses. The deterministic sensitivity analysis compared FMT via enema (the least cost saving FMT route) with VTP (the comparator with the second lowest cost and highest health benefit). It found that the largest cost drivers were the resolution probability for FMT via enema and VTP, followed by the hospital stay for any cases of C. difficile infection in subsequent cycles. The results of the probabilistic sensitivity analysis showed that FMT is estimated to be cost saving 96% to 100% of the time compared with antibiotic treatment. The EAC also did 5 scenario analyses. FMT remained cost saving in all of them: